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A03-Research Projects

Paper | Original Paper

2017

Tatsuaki Tsuruyama,
Kinetic Stability Analysis of Protein Assembly on the Center Manifold around the Critical Point.,
BMC Systems Biology, in press (2017).

[Summary] Background: Non-linear kinetic analysis is a useful method for illustration of the dynamic behavior of cellular biological systems. To date, center manifold theory (CMT) has not been sufficiently applied for stability analysis of biological systems. The aim of this study is to demonstrate the application of CMT to kinetic analysis of protein assembly and disassembly, and to propose a novel framework for nonlinear multi-parametric analysis. We propose a protein assembly model with nonlinear kinetics provided by the fluctuation in monomer concentrations during their diffusion. Results: When the diffusion process of a monomer is self-limited to give kinetics non-linearity, numerical simulations suggest the probability that the assembly and disassembly oscillate near the critical point. We applied CMT to kinetic analysis of the center manifold around the critical point in detail, and successfully demonstrated bifurcation around the critical point, which explained the observed oscillation.Conclusions: The stability kinetics of the present model based on CMT illustrates a unique feature of protein assembly, namely non-linear behavior. Our findings are expected to provide methodology for analysis of biological systems.

Yuto Hosaka, Kento Yasuda, Isamu Sou, Ryuichi Okamoto, and Shigeyuki Komura,
Thermally driven elastic micromachines,
Journal of the Physical Sciety of Japan 86, 113801/1-4 (2017).

[Summary] We discuss the directional motion of an elastic three-sphere micromachine in which the spheres are in equilibrium with independent heat baths having different temperatures.Even in the absence of prescribed motion of springs, such a micromachine can gain net motion purely because of thermal fluctuations. A relation connecting the average velocity and the temperatures of the spheres is analytically obtained. This velocity can also be expressed in terms of the average heat flows in the steady state. Our model suggests a new mechanism for the locomotion of micromachines in nonequilibrium biological systems.

Kenji Nishizawa, Marcel Bremerich, Heev Ayade, Christoph F. Schmidt, Takayuki Ariga, Daisuke Mizuno*,
Feedback-tracking microrheology in living cells,
SCIENCE ADVANCES 3, e1700318 (2017).

Shoko Uemoto, Taro Toyota, Luca Chiari, Tomonori Nomoto, *Masanori Fujinami,,
Assemblies of molecular aggregates in the blebbing motion of an oil droplet on an aqueous solution containing surfactant,
Colloids and Surfaces A: Physicochemical and Engineering Aspects 529, 373-379 (2017).

[Summary] The characteristic amoeboid behavior of an oil droplet (decane with dissolved palmitic acid) on an aqueous phase containing a surfactant (stearyltrimethylammonium chloride) has been investigated and discussed. The formation and motion of assemblies of molecular aggregates were observed with the aid of a range of particle tracers. The quasi-elastic laser scattering method was employed to measure the surface tension of the aqueous phase as a function of time. From those measurements we found that the amoeboid behavior occurs in three stages. First, molecular aggregates formed at the oil-water interface and subsequently spread and absorbed at the aqueous surface thanks to a convective flow due to the Marangoni effect. In the second stage, the whole aqueous surface was saturated with those molecular aggregates and a phase transition to a liquid condensed monolayer membrane occurred. Finally, domains formed at the bottom of the oil droplet with permeable boundaries composed of branch-shaped assemblies of molecular aggregates. Blebs grew in those parts of the oil droplet rim with high accumulation of molecular aggregates.

Atsuji Kodama, Yuka Sakuma, *Masayuki Imai, Toshihiro Kawakatsu, Nicolas Puff, and Miglena I. Angelova,
Migration of Phospholipid Vesicles Can Be Selectively Driven by Concentration Gradients of Metal Chloride Solutions,
Langmuir 33, 10698-10706 (2017).

[Summary] We have investigated the migrations of phospholipid vesicles under the concentration gradients of metal ions. We micro-injected metal chloride solutions, monovalent (NaCl and KCl), divalent (CaCl2 and MgCl2), and trivalent (LaCl3) salts, toward phospholipid giant vesicles (GVs) composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). For NaCl, CaCl2, and MgCl2 solutions, the GVs migrated straight toward the tip of the micro-pipette in response to the concentration gradients, whereas for KCl and LaCl3, GVs moved to the opposite direction. Our motion tracking of lipid domains in a vesicle membrane showed no unidirectional flow in the membrane during the vesicle migration, indicating that the Marangoni mechanism is not responsible for the observed vesicle migration. We calculated the diffusiophoretic velocities for symmetric and asymmetrical electrolytes by solving the Stokes’ equation numerically. The theoretical diffusiophoretic velocities well described the observed migration velocities. Thus we can control the migration of vesicle in response to the concentration gradient by adapting the electrolytes and the lipids.

Kazusa Beppu, Ziane Izri, Jun Gohya, Kanta Eto, Masatoshi Ichikawa, *Yusuke T. Maeda,
Geometry-driven collective ordering of bacterial vortices,
Soft Matter 13, 5038-5043 (2017).

[Summary] Controlling the phases of matter is a challenge that spans from condensed materials to biological systems. Here, by imposing a geometric boundary condition, we study the controlled collective motion of Escherichia coli bacteria. A circular microwell isolates a rectified vortex from disordered vortices masked in the bulk. For a doublet of microwells, two vortices emerge but their spinning directions show transition from parallel to anti-parallel. A Vicsek-like model for confined self-propelled particles gives the point where the two spinning patterns occur in equal probability and one geometric quantity governs the transition as seen in experiments. This mechanism shapes rich patterns including chiral configurations in a quadruplet of microwells, thus revealing a design principle of active vortices.

Hiroaki Ito, Masahiro Makuta, Yukinori Nishigami, and *Masatoshi Ichikawa,
Active materials integrated with actomyosin,
Journal of the Physical Society of Japan 86, 101001/1-6 (2017).

[Summary] Muscles are the engine of our body, and actomyosin is the engine of a cell. Both muscle and the actomyosin use thesame proteins, namely, actin, and myosin, which are the pair of cytoskeleton and motor proteins generating a force torealize deformation. The properties of force generation by actomyosin at a single-molecule level have been studied formany years. Moreover, the active properties of higher-order structures integrated by actomyosin are attracting theattention of researchers. Here, we review the recent progress in the study of reconstituted actomyosin systems in vitrotoward real-space models of nonequilibrium systems, collective motion, biological phenomena, and active materials.

*Yasuyuki Kimura,
Hydrodynamically Induced Collective Motion of Optically Driven Colloidal Particles on a Circular Path,
Journal of the Physical Society of Japan 86, 101003/1-7 (2017).

[Summary] Among typical active matter such as self-propelled micro-objects, the characteristic collective motion originating from the hydrodynamic interaction between constituents has been observed in both biological and artificial systems. In illustrating such motion of micrometer-size particles in a one-dimensional optically driven system with a low Reynolds number, we highlight the importance of the hydrodynamic interaction. We show the appearance of regular stationary and dynamic arrangements resembling “crystals” or “clusters” observed in the equilibrium state. A transition in the collective motion has been observed by varying the hydrodynamic interaction in a system of two particle sizes and in a spatially confined system. An optical manipulation technique and the related hydrodynamic equations are also discussed.

Masami Noda, Yue Ma, Yuko Yoshikawa, Tadayuki Imanaka, Toshiaki Mori, Masakazu Furuta, Tatsuaki Tsuruyama and Kenichi Yoshikawa,
A single-molecule assessment of the protective effect of DMSO against DNA double-strand breaks induced by photo-and g-ray-irradiation, and freezing,
Scientific Reports 7, 8557/ 1-8 (2017).

[Summary] Dimethyl sulfoxide (DMSO) is widely used as a cryoprotectant for organs, tissues, and cell suspension in storage. In addition, DMSO is known to be a useful free radical scavenger and a radio-protectant. To date, many in vitro assays using cultured cells have been performed for analysing the protective effect of DMSO against genomic DNA damage; however, currently it has been rather difficult to detect DNA double strand breaks (DSBs) in a quantitative manner. In the present study, we aimed to observe the extent of DNA damage by use of single molecular observation with a fluorescence microscope to evaluate DSBs induced by photo- and γ-ray-irradiation, or freeze/thawing in variable concentrations of DMSO. As a result, we found that 2% DMSO conferred the maximum protective effect against all of the injury sources tested, and these effects were maintained at higher concentrations. Further, DMSO showed a significantly higher protective effect against freezing-induced damage than against photo- and γ-ray-irradiation-induced damage. Our study provides significant data for the optimization of DNA cryopreservation with DMSO, as well as for the usage of DNA as the protective agent against the injuries caused by active oxygen and radiations.

Marcel Hörning, François Blanchard, Akihiro Isomura, andKenichi Yoshikawa,
Dynamics of spatiotemporal line defects and chaos control in complex excitable systems,
Scientific Reports 7, 7757/1-9 (2017).

[Summary] Spatiotemporal pattern formation governs dynamics and functions in various biological systems. In the heart, excitable waves can form complex oscillatory and chaotic patterns even at an abnormally higher frequency than normal heart beats, which increase the risk of fatal heart conditions by inhibiting normal blood circulation. Previous studies suggested that line defects (nodal lines) play a critical role in stabilizing those undesirable patterns. However, it remains unknown if the line defects are static or dynamically changing structures in heart tissue. Through in vitro experiments of heart tissue observation, we reveal the spatiotemporal dynamics of line defects in rotating spiral waves. We combined a novel signaling over-sampling technique with a multi-dimensional Fourier analysis, showing that line defects can translate, merge, collapse and form stable singularities with even and odd parity while maintaining a stable oscillation of the spiral wave in the tissue. These findings provide insights into a broad class of complex periodic systems, with particular impact to the control and understanding of heart diseases.

Kento Yasuda, Yuto Hosaka, Mizuki Kuroda, Ryuichi Okamoto, and *Shigeyuki Komura,
Elastic three-sphere microswimmer in a viscous fluid,
Journal of the Physical Sciety of Japan 86, 093801/1-4 (2017).

[Summary] We discuss the dynamics of a generalized three-sphere microswimmer in which the spheres are connected by two elastic springs. The natural length of each spring is assumed to undergo a prescribed cyclic change. We analytically obtain the average swimming velocity as a function of the frequency of cyclic change in the natural length. In the low- frequency region, the swimming velocity increases with frequency, and its expression reduces to that of the original three-sphere model by Najafi and Golestanian. Conversely, in the high-frequency region, the average velocity decreases with increasing frequency. Such behavior originates from the intrinsic spring relaxation dynamics of an elastic swimmer moving in a viscous fluid.

*Ryuichi Okamoto, Shigeyuki Komura, and Jean-Baptiste Fournier,
Dynamics of a bilayer membrane coupled to a two-dimensional cytoskeleton: Scale transfers of membrane deformations,
Physical Review E 96, 012416/1-10 (2017).

[Summary] We theoretically investigate the dynamics of a floating lipid bilayer membrane coupled with a two-dimensional cytoskeleton network, taking into account explicitly the intermonolayer friction, the discrete lattice structure of the cytoskeleton, and its prestress. The lattice structure breaks lateral continuous translational symmetry and couples Fourier modes with different wave vectors. It is shown that within a short time interval a long-wavelength deforma- tion excites a collection of modes with wavelengths shorter than the lattice spacing. These modes relax slowly with a common renormalized rate originating from the long-wavelength mode. As a result, and because of the prestress, the slowest relaxation is governed by the intermonolayer friction. Conversely, and most interestingly, forces applied at the scale of the cytoskeleton for a sufficiently long time can cooperatively excite large-scale modes.

Aoi Yoshida, Shoto Tsuji, Hiroaki Taniguchi, Takahiro Kenmotsu, Koichiro Sadakane, *Kenichi Yoshikawa,
Manipulating Living Cells to Construct a 3D Single-Cell Assembly without an Artificial Scaffold,
Polymers 9, 319/2-10 (2017).

[Summary] Artificial scaffolds such as synthetic gels or chemically-modified glass surfaces that have often been used to achieve cell adhesion are xenobiotic and may harm cells. To enhance the value of cell studies in the fields of regenerative medicine and tissue engineering, it is becoming increasingly important to create a cell-friendly technique to promote cell-cell contact. In the present study, we developed a novel method for constructing stable cellular assemblies by using optical tweezers in a solution of a natural hydrophilic polymer, dextran. In this method, a target cell is transferred to another target cell to make cell-cell contact by optical tweezers in a culture medium containing dextran. When originally non-cohesive cells are held in contact with each other for a few minutes under laser trapping, stable cell-cell adhesion is accomplished. This method for creating cellular assemblies in the presence of a natural hydrophilic polymer may serve as a novel next-generation 3D single-cell assembly system with future applications in the growing field of regenerative medicine.

Isamu Sou, Ryuichi Okamoto, Shigeyuki Komura, and Jean Wolff,
Coexistences of lamellar phases in ternary surfactant solutions,
Soft Materials 15, 1-10 (2017).

[Summary] We theoretically investigate the coexistences of lamellar phases both in binary and in ternary surfactant solutions. The previous free energy of a lamellar stack is extended to take into account the translational entropy of membrane segments. The obtained phase diagram for binary surfactant solutions (surfactant/water mixtures) shows a phase separation between two lamellar phases and also exhibits a critical point. For lamellar phases in ternary surfactant solutions (surfactant/surfactant/water mixtures), we explore the possible phase behaviors and show that the phase diagrams exhibit various three-phase regions as well as two-phase regions in which different lamellar phases coexist. We also find that finite surface tension suppresses the undulation fluctuations of membranes and leads to a wider three-phase and two-phase coexistence regions.

Daigo Yamamoto, Ryota Yamamoto, Takahiro Kozaki, Akihisa Shioi, Syuji Fujii and *Kenichi Yoshikawa,
Periodic Motions of Solid particles with Various Morphology under a DC Electrostatic Field,
Chemistry Letters 46, 1470-1472 (2017).

[Summary] This paper describes the generation of periodic motions of solid particle in an oil phase under a direct current (DC) voltage. We found that a dimer and trimer composed of spherical polystyrene (PS) particles exhibit a novel periodic motion, spin. These particles maintain their stable motion without any support from mechanical devices such as rotational axes or electronic switching devices. We expect that the simple DC micromotion is applicable for mechanical and fluidic devices employing microrobots and microfluidics.

Keisuke Mae, Hidetoshi Toyama, Erika Okita Nawa, Daigo Yamamoto, Akihisa Shioi, Yongjun Chen, *Kenichi Yoshikawa, Fumiyuki Toshimitsu, Naotoshi Nakashima and Kazunari Matsuda,
Self-Organized Micro-Spiral of Single-Walled Carbon Nanotubes,
Scientific Reports 7, 5267/1-12 (2017).

[Summary] Single-walled carbon nanotubes (SWCNTs) are reported to spontaneously align in a rotational pattern by drying a liquid droplet of toluene containing polyfluorene as a dispersant. By situating a droplet of an SWCNT solution around a glass bead, spiral patterns are generated. The parallel alignment of SWCNTs along one stripe of such a pattern is confirmed using scanning electron microscopy and polarized optical microscopy. The orientation order increases toward the outer edge of a stripe. The stripe width in the pattern is proportional to the solute concentration, and the width and position of the stripes follow geometric sequences. The growth of the rotational pattern is also observed in real time. The process of spiral pattern formation is visualized, indicating the role of the annihilation of counter-traveling accompanied by continuous depinning. The geometric sequences for the stripe width and position are explained by the near-constant traveling speed and solute enrichment at the droplet periphery.

Yuta Shimizu, Yuko Yoshikawa, Takahiro Kenmotsu, Seiji Komeda and *Kenichi Yoshikawa,
Conformational transition of DNA by dinuclear Pt(II) complexes causes cooperative inhibition of gene expression,
Chemical Physics Letters 678, 123-129 (2017).

[Summary] Recently, it was reported that a cationic tetrazolato-bridged dinuclear Pt(II) complex, 5-H-Y, is a promising anticancer drug candidate. Here, we investigated the effects of a series of tetrazolato-bridged dinuclear Pt(II) complexes on the higher-order structure of DNA by using fluorescence and atomic force microscopies. The results showed that these dinuclear Pt(II) complexes cause marked shrinkage on the conformation of genomic DNA. We also found highly cooperative inhibitory effects of these drugs on in vitro gene expression. The unique mechanism of action of these dinuclear Pt(II) complexes is discussed in terms of their bridging effect on DNA segments.

Hideo Shindou, Hideto Koso, Junko Sasak, Hiroki Nakanishi, Hiroshi Sagara,h Koh M. Nakagawa, Yoshikazu Takahashi, Daisuke Hishikawa, Yoshiko Iizuka-Hishikawa, Fuyuki Tokumasu, Hiroshi Noguchi, Sumiko Watanabe, Takehiko Sasaki, and Takao Shimizu,
Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells,
Journal of Biological Chemistry 292, 12054-12064 (2017).

[Summary] Docosahexaenoic acid (DHA) has essential roles in photoreceptor cells in the retina and is therefore crucial to healthy vision. Although the influence of dietaryDHAon visual acuity is well known and the retina has an abundance of DHA-containing phospholipids (PL-DHA), the mechanisms associated with DHA’s effects on visual function are unknown. We previously identified lysophosphatidic acid acyltransferase 3 (LPAAT3) as a PL-DHA biosynthetic enzyme. Here, using comprehensive phospholipid analyses and imaging mass spectroscopy, we found that LPAAT3 is expressed in the inner segment of photoreceptor cells and that PL-DHA disappears from the outer segment in the LPAAT3-knock-out mice. Dynamic light-scattering analysis of liposomes and molecular dynamics simulations revealed that the physical characteristics ofDHAreduced membrane-bending rigidity. Following loss of PL-DHA, LPAAT3-knock-out mice exhibited abnormalities in the retinal layers,such as incomplete elongation of the outer segment and decreased thickness of the outer nuclear layers and impaired visual function, as well as disordered disc morphology in photoreceptor cells. Our results indicate that PL-DHA contributes to visual function by maintaining the disc shape in photoreceptor cells and that this is a function of DHA in the retina. This study thus provides the reason why DHA is required for visual acuity and may help inform approaches for overcoming retinal disorders associated with DHA deficiency or dysfunction.

Yuto Hosaka, Kento Yasuda, Ryuichi Okamoto, *Shigeyuki Komura,
Lateral diffusion induced by active proteins in a biomembrane,
Physical Review E 95, 052407/1-10 (2017).

[Summary] We discuss the hydrodynamic collective effects due to active protein molecules that are immersed in lipid bilayer membranes and modeled as stochastic force dipoles. We specifically take into account the presence of the bulk solvent which surrounds the two-dimensional fluid membrane. Using the generalized membrane mobility tensors, we estimate the active diffusion coefficient and the drift velocity as a function of the size of a diffusing object.

Kanta Tsumoto and *Kenichi Yoshikawa,
The Aqueous Two Phase System (ATPS) Deserves Plausible Real-World Modeling for the Structure and Function of Living Cells,
MRS Advances 2, 2407-2413 (2017).

[Summary] An aqueous two phase system (ATPS) is composed of binary hydrophilic polymers, for example, polyethylene glycol (PEG) and dextran, under an immiscible condition, and can also exhibit micro-segregation to produce cell-sized microcompartments like water-in-water microdroplets. Without membranes, interestingly, the microdroplet can serve as a micro-vessel (reactor) that contains various biochemical macromolecules like DNAs and proteins. We here present that PEG/dextran ATPS micro-segregation can provide an effective soft boundary to separate these biochemical macromolecules from the external environment. Trapped DNAs and proteins were concentrated inside such small spaces, and therefore, their interaction could be highly promoted to cause passive aggregation and controlled cross-linking if a certain cross-linker was added. We believe that the ATPS microdroplets might be associated with complicated structures and functions of living cells.

Naoko Ueno, Taisuke Banno, Arisa Asami, Yuki Kazayama, Yuya Morimoto, Toshihisa Osaki, Shoji Takeuchi, Hiroyuki Kitahata, *Taro Toyota,
Self-propelled motion of monodisperse underwater oil droplets formed by a microfluidic device,
Langmuir 33, 5393-5397 (2017).

[Summary] We evaluated the speed profile of self-propelled underwater oil droplets comprising a hydrophobic aldehyde derivative in terms of their diameter and the surrounding surfactant concentration using a microfluidic device. We found that the speed of the oil droplets is dependent on not only the surfactant concentration but also the droplet size in a certain range of the surfactant concentration. This tendency is interpreted in terms of combination of the oil and surfactant affording spontaneous emulsification in addition to the Marangoni effect.

Hiroshi Noguchi and Jean-Baptiste Fournier,
Membrane structure formation induced by two types of banana-shaped proteins,
Soft Matter 13, 4099-4111 (2017).

[Summary] The assembly of banana-shaped rodlike proteins on membranes and the associated membrane shape transformations are investigated by analytical theory and coarse-grained simulations. The membranemediatedinteractions between two banana-shaped inclusions are derived theoretically using a point-like formalism based on fixed anisotropic curvatures, both for zero surface tension and for finite surface tension. On a larger scale, the interactions between the assemblies of such rodlike inclusions are determined analytically. Meshless membrane simulations are performed in the presence of a largenumber of inclusions of two types, corresponding to the curved rods of opposite curvatures, both for flat membranes and vesicles. Rods of the same type aggregate into linear assemblies perpendicular to the rod axis, leading to membrane tubulation. However, rods of the other type, those of opposite curvature, are attracted to the lateral sides of these assemblies, and stabilize a straight bump structure that prevents tubulation. When the two types of rods have almost opposite curvatures, the bumps attract one another, forming a striped structure. Positive surface tension is found to stabilize stripe formation. The simulation results agree well with the theoretical predictions provided the point-like curvatures of the model are scaled-down to account for the effective flexibility of the simulated rods.

Kento Yasuda, Ryuichi Okamoto, and *Shigeyuki Komura,
Swimmer-microrheology,
Journal of the Physical Society of Japan 86, 043801/1-4 (2017).

[Summary] We discuss the locomotion of a three-sphere microswimmer in a viscoelastic medium and propose a new type of active microrheology. We derive a relation that connects the average swimming velocity and the frequency-dependent viscosity of the surrounding medium. In this relation, the viscous contribution can exist only when the time-reversal symmetry is broken, whereas the elastic contribution is present only when the structural symmetry of the swimmer is broken. Purcell’s scallop theorem breaks down for a three-sphere swimmer in a viscoelastic medium.

Kento Yasuda, Ryuichi Okamoto, and *Shigeyuki Komura,
Anomalous diffusion in viscoelastic media with active force dipoles,
Physical Review E 95, 032417/1-14 (2017).

[Summary] With the use of the ``two-fluid model", we discuss anomalous diffusion induced by active force dipoles in viscoelastic media. Active force dipoles, such as proteins and bacteria, generate non-thermal fluctuating flows that lead to a substantial increment of the diffusion. Using the partial Green's function of the two-fluid model, we first obtain passive (thermal) two-point correlation functions such as the displacement cross-correlation function between the two point particles separated by a finite distance. We then calculate active (non-thermal) one-point and two-point correlation functions due to active force dipoles.The time correlation of a force dipole is assumed to decay exponentially with a characteristic time scale. We show that the active component of the displacement cross-correlation function exhibits various crossovers from super-diffusive to sub-diffusive behaviors depending on the characteristic timescales and the particle separation. Our theoretical results are intimately related to the microrheology technique to detect fluctuations in non-equilibrium environment.

Swaminath Bharadwaj, *Palakurissi B. Sunil Kumar, Shigeyuki Komura, Abhijit P. Deshpande,
Spherically symmetric solvent is sufficient to explain lower critical solution temperature in polymer solutions,
Macromolecular Theory and Simulations 26, 1600073/1-11 (2017).

[Summary] The mechanism of the lower critical solution temperature (LCST) in thermoresponsive polymer solutions has been studied. The simulation model includes solvent explicitly and thus accounts for solvent interactions and entropy directly. The theoretical model consists of a single chain polymer in an implicit solvent where the effect of solvent is included through the intrapolymer solvophobic potential proposed by Kolomeisky and Widom. The results of this study indicate that the LCST behavior is determined by the competition between the mean energy difference between the bulk and bound solvent, and the entropy loss due to the bound solvent.

*Tomo Kurimura, Yoshiko Takenaka, Satoru Kidoaki, and *Masatoshi Ichikawa,
Fabrication of gold microwires by drying goldnanorods suspensions,
Advanced Materials Interfaces 1601125, 1-5 (2017).

[Summary] The ramification pattern of gold nanorods is fabricated by drying its suspensionbetween two glass slides. The aspect ratio of the nanorods and the pinningon the contact line among air, water, and substrate are important. Afterbeing baked, this pattern also conducts electricity. The method of patterningis useful for microwiring without the additional need to pattern the wires intospecific shapes.

Kento Yasuda, Ryuichi Okamoto, *Shigeyuki Komura, and Alexander S. Mikhailov,
Localization and diffusion of tracer particles in viscoelastic media with active force dipoles,
EPL 117, 38001/1-7 (2017).

[Summary] The two-fluid model of a gel is considered where active macromolecules, described as force dipoles, cyclically operate both in the elastic and the fluid components. Through coarse-graining, effective equations of motions for idealized tracer particles displaying local deformations and local fluid flows are derived. The equation for deformation tracers coincides with the earlier phenomenological model and thus confirms it. For flow tracers, diffusion enhancement caused by active force dipoles in the fluid component, and thus due to metabolic activity, is found.

Rinko Kubota, Yusuke Yamashita, Takahiro Kenmotsu, Yuko Yoshikawa, Kenji Yoshida, Yoshiaki Watanabe, Tadayuki Imanaka and *Kenichi Yoshikawa,
Double-Strand Breaks in Genome-Sized DNA Caused by Ultrasound,
ChemPhysChem 18, 959-964 (2017).

[Summary] DNA double-strand breaks (DSBs) caused by ultrasound were evaluated in a quantitative manner by single-molecule fluorescence microscopy. We compared the effect of time-interval (or pulse) sonication to that of continuous wave (CW) sonication at a fixed frequency of 30 kHz. Pulses caused fewer DSBs than CW sonication under the same total input ultrasound energy when the pulse repetition period was above the order of a second. In contrast, pulses caused more DSBs than CW sonication for pulse widths shorter than a second. These effect of ultrasound on DNA were interpreted in terms of the time-dependent decay in the probability of breakage during the duration of a pulse. We propose a simple phenomenological model by considering a characteristic decay in the probability of DSBs during single-pulse sonication, which reproduces the essence of the experimental trend. In addition, a data analysis revealed a characteristic scaling behavior between the number of pulses and the number of DSBs.

Takuro Itoh, *Taro Toyota, Hiroyuki Higuchi, Michio M. Matsushita, Kentaro Suzuki, and *Tadashi Sugawara,
Cycle of charge carrier states with formation and extinction of a floating gate in an ambipolar tetracyanoquaterthienoquinoid-based field-effect transistor,
Chemical Physics Letters 671, 71-77 (2017).

[Summary] A tetracyanoquaterthienoquinoid (TCT4Q)-based field effect transistor is characterized by the ambipolar transfer characteristics and the facile shift of the threshold voltage induced by the bias stress. The trapping and detrapping kinetics of charge carriers was investigated in detail by the temperature dependence of the decay of source-drain current (ISD). We found a repeatable formation of a molecular floating gate is derived from a ‘charge carrier-and-gate’ cycle comprising four stages, trapping of mobile carriers, formation of a floating gate, induction of oppositely charged mobile carriers, and recombination between mobile and trapped carriers to restore the initial state.

Tomohiro G. Noguchi, *Yasutaka Iwashita, and Yasuyuki Kimura,
Dependence of the Internal Structure on Water/Particle Volume Ratio in an Amphiphilic Janus Particle–Water–Oil Ternary System: From Micelle-like Clusters to Emulsions of Spherical Droplets,
Langmuir 33, 1030-1036 (2017).

[Summary] Amphiphilic Janus particles (AJP), composed of hydrophilic and hydrophobic hemispheres, are one of the simplest anisotropic colloids, and they exhibit higher surface activities than particles with homogeneous surface properties. Consequently, a ternary system of AJP, water, and oil can form extremely stable Pickering emulsions, with internal structures that depend on the Janus structure of the particles and the system composition. However, the detail of these structures has not been fully explored, especially for the composition range where the amount of the minority liquid phase and AJP are comparable, where one would expect the Janus characteristics to be directly reflected. In this study, we varied the volume ratio of the particles and the minority liquid phase, water, by 2 orders of magnitude around the comparable composition range, and observed the resultant structures at the resolution of the individual particle dimensions by optical microscopy. When the volume ratio of water is smaller than that of the Janus particles, capillary interactions between the hydrophilic hemispheres of the particles induce micelle-like clusters in which the hydrophilic sides of the particles face inward. With increasing water content, these clusters grow into a rodlike morphology. When the water volume exceeds that of the particles, the structure transforms into an emulsion state composed of spherical droplets, colloidosomes, because of the surface activity of particles at the liquid–liquid interface. Thus, we found that a change in volume fraction alters the mechanism of structure formation in the ternary system, and large resulting morphological changes in the self-assembled structures reflect the anisotropy of the particles.

Seiji Komeda, Hiroki Yoneyama, Masako Uemura, Akira Muramatsu, Wakao Fukuda, Tadayuki Imanaka, Toshio Kanbe, Yuko Yoshikawa and *Kenichi Yoshikawa,
Specific Conformational Change in Giant DNA Caused by Anticancer Tetrazolato-Bridged Dinuclear Platinum(II) Complexes: Middle-Length Alkyl Substituents Exhibit Minimum Effect,
Inorganic Chemistry 56, 802–811 (2017).

[Summary] Derivatives of the highly antitumor-active compound [{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)]2+ (5-H-Y), which is a tetrazolato-bridged dinuclear platinum(II) complex, were prepared by substituting a linear alkyl chain moiety at C5 of the tetrazolate ring. The general formula for the derivatives is [{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]2+, where R is (CH2)nCH3 and n = 0 to 8 (complexes 1–9). The cytotoxicity of complexes 1–4 in NCI-H460 human non-small-cell lung cancer cells decreased with increasing alkyl chain length, and those of complexes 5–9 increased with increasing alkyl chain length. That is, the in vitro cytotoxicity of complexes 1–9 was found to have a U-shaped association with alkyl chain length. This U-shaped association is attributable to the degree of intracellular accumulation. Although circular dichroism spectroscopic measurement indicated that complexes 1–9 induced comparable conformational changes in the secondary structure of DNA, the tetrazolato-bridged complexes induced different degrees of DNA compaction as revealed by a single DNA measurement with fluorescence microsopy, which also had a U-shaped association with alkyl chain length that matched the association observed for cytotoxicity. Complexes 7–9, which had alkyl chains long enough to confer surfactant-like properties to the complex, induced DNA compaction 20 or 1000 times more efficiently than 5-H-Y or spermidine. A single DNA measurement with transmission electron microscopy revealed that complex 8 formed large spherical self-assembled structures that induced DNA compaction with extremely high efficiency. This result suggests that these structures may play a role in the DNA compaction that was induced by the complexes with the longer alkyl chains. The derivatization with a linear alkyl chain produced a series of complexes with unique cellular accumulation and DNA conformational change profiles and a potentially useful means of developing next-generation platinum-based anticancer drugs. In addition, the markedly high ability of these complexes to induce DNA compaction and their high intracellular accumulation emphasized the difference in mechanism of action from platinum-based anticancer drugs

2016

T. V. Sachin Krishnan, Ryuichi Okamoto, and *Shigeyuki Komura,
Relaxation dynamics of a compressible bilayer vesicle containing highly viscous fluid,
Physical Review E 94, 062414/1-14 (2016).

[Summary] We study the relaxation dynamics of a compressible bilayer vesicle with an asymmetry in the viscosity of the inner and outer fluid medium. A higher fluid viscosity inside the vesicle shifts the crossover mode between the bending and the slipping to a larger value. As the vesicle parameters approach the unstable regions, the relaxation dynamics is dramatically slowed down, and the corresponding mode structure changes significantly.

Masa Tsuchiya, Alessandro Giuliani, Midori Hashimoto, Jekaterina Erenpreisa and *Kenichi Yoshikawa,
Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change,
Plos One, 1-47 (2016).

Akira Muramatsu, Yuta Shimizu, Yuko Yoshikawa, Wakao Fukuda, Naoki Umezawa, Yuhei Horai, Tsunehiko Higuchi, Shinsuke Fujiwara, Tadayuki Imanaka and *Kenichi Yoshikawa,
Naturally occurring branched-chain polyamines induce a crosslinked meshwork structure in a giant DNA,
The Journal of Chemical Physics 145, 235103/1-7 (2016).

[Summary] We studied the effect of branched-chain polyamines on the folding transition of genome-sized DNA molecules in aqueous solution by the use of single-molecule observation with fluorescence microcopy. Detailed morphological features of polyamine/DNA complexes were characterized by atomic force microscopy (AFM). The AFM observations indicated that branched-chain polyamines tend to induce a characteristic change in the higher-order structure of DNA by forming bridges or crosslinks between the segments of a DNA molecule. In contrast, natural linear-chain polyamines cause a parallel alignment between DNA segments. Circular dichroism measurements revealed that branched-chain polyamines induce the A-form in the secondary structure of DNA, while linear-chain polyamines have only a minimum effect. This large difference in the effects of branched- and linear-chain polyamines is discussed in relation to the difference in the manner of binding of these polyamines to negatively charged double-stranded DNA.

*Hayato Shiba, Yasunori Yamada, Takeshi Kawasaki, and Kang Kim,
Unveiling Dimensionality Dependence of Glassy Dynamics: 2D Infinite Fluctuation Eclipses Inherent Structural Relaxation,
Physical Review Letters 117, 245701/1-6 (2016).

[Summary] By using large-scale molecular dynamics simulations, the dynamics of two-dimensional (2D) supercooled liquids turns out to be dependent on the system size, while the size dependence is not pronounced in three-dimensional (3D) systems. It is demonstrated that the strong system-size effect in 2D amorphous systems originates from the enhanced fluctuations at long wavelengths , which are similar to those of 2D crystal phonons. This observation is further supported by the frequency dependence of the vibrational density of states, consisting of the Debye approximation in the low-wave-number limit. However, the system-size effect in the intermediate scattering function becomes negligible when the length scale is larger than the vibrational amplitude. This suggests that the finite-size effect in a 2D system is transient and also that the structural relaxation itself is not fundamentally different from that in a 3D system. In fact, the dynamic correlation lengths estimated from the bond-breakage function, which do not suffer from those enhanced fluctuations, are not size dependent in either 2D and or 3D systems.

*Tatsuaki Tsuruyama, Takuya Hiratsuka, Wulamujiang Aini, Takuro Nakamura,
STAT5A modulates chemokine receptor CCR6 expression and enhances pre-B cell growth in a CCL20-dependent manner. J cellular biochemistry.,
J Cell Biochem 117, 2630-2642 (2016).

[Summary] Signal transducer and activator of transcription 5A (STAT5A) contributes to B-cell responses to cytokines through suppressor of cytokine signaling (Socs) genes in innate immunity. However, its direct roles in B-cell responses to chemokines are poorly understood. In this study, we examined the role of STAT5A in the innate immune response. We found that STAT5A upregulated the transcription of C-C motif receptor 6 (Ccr6) to induce responses to its ligand, CCL20. STAT5A transcriptional activity proceeded through binding to the interferon-g activation site (GAS) element in the CCR6 promoter in the genome of pre-B cells. High levels of STAT5A and CCR6 increased CCL20-dependent colony growth of pre-B cells. In human B-lymphoblastic lymphoma with inflammation, STAT5A phosphorylation was correlated with CCR6 expression STAT5A enhanced the response of pre-B cells to CCL20 to promote their growth.

Koh M. Nakagawa and *Hiroshi Noguchi,
Nonuniqueness of local stress of three-body potentials in molecular simulations,
Physical Review E 94, 053304/1-11 (2016).

[Summary] Microscopic stress fields arewidely used in molecular simulations to understand mechanical behavior.Recently,decomposition methods of multibody forces to central force pairs between the interacting particles have beenproposed. Here, we introduce a force center of a three-body potential and propose different force decompositionsthat also satisfy the conservation of translational and angular momentum. We compare the force decompositionsby stress-distribution magnitude and discuss their difference in the stress profile of a bilayer membrane by usingcoarse-grained and atomistic molecular dynamics simulations.

*Shunsuke F. Shimobayashi, Mafumi Hishida, Tomo Kurimura and Masatoshi Ichikawa,
Nanoscale hydration dynamics of DNA-lipid blend dry films: DNA-size dependency,
Physical Chemistry Chemical Physics 2016, 18, 31664-31669 (2016).

[Summary] In this study, nanoscale hydration dynamics of DNA–lipid blend dry films are investigated *via* small angle X-ray diffraction. Compared to the hydration of lipid films, fragmented short DNA strands and counterions in stacked lipid layers dramatically accelerate both the relaxation of the lamellar distance to a metastable interval and the subsequent peeling-off process of lipid bilayers. Moreover, genome-sized long DNA and counterions accelerate the relaxation process, but suppress the peeling-off process and simultaneously induce a damped-oscillation of the lamellar interval; this is probably due to the viscoelastic properties of the entangled long DNA dissolved in hydrated water between the stacked lipid bilayers. This study's findings can pave the way for producing cell-sized liposomes, which efficiently encapsulate any arbitrary sized DNA through natural swelling.

Jean Wolff, *Shigeyuki Komura, and David Andelman,
Budding transition of asymmetric two-component lipid domains,
Physical Review E 94, 032406/1-8 (2016).

[Summary] We propose a model that accounts for the budding transition of asymmetric two-component lipid domains, where the two monolayers (leaflets) have different average compositions controlled by independent chemical potentials. Within a mean-field treatment, we obtain various phase diagrams containing fully budded, dimpled, and flat states as a function of the two leaflet compositions. The global phase behavior is analyzed, and depending on system parameters, the phase diagrams include one-phase, two-phase, and three-phase regions.

Taisuke Banno, Arisa Asami, Naoko Ueno, Hiroyuki Kitahata, Yuki Koyano, Kouichi Asakura, *Taro Toyota,
Deformable self-propelled micro-object comprising underwater oil droplets,
Scientific Reports 6, 31292 (2016).

[Summary] The self-propelled motion with deformation of micrometer-sized soft matter in water has potential application not only for underwater carriers or probes in very narrow spaces but also for understanding cell locomotion in terms of non-equilibrium physics. As far as we know, there have been no reports about micrometer-sized self-propelled soft matter mimicking amoeboid motion underwater. Here, we report an artificial molecular system of underwater oil droplets exhibiting self-propelled motion with deformation as an initial experimental model. We describe the heterogeneity in a deformable self-propelled oil droplet system in aqueous and oil phases and at their interface based on the behavior and interaction of surfactant and oil molecules. The current results have great importance for scientific frontiers such as developing deformable micro-swimmers and exploring the emergence of self-locomotion of oil droplet-type protocells.

Jerzy Górecki, Jonna N Gorecka, Bogdan Nowakowski, Hiroshi Ueno, Tatsuaki Tsuruyama and *Kenichi Yoshikawa,
Sensing Parameter of a Time Dependent Inflow with an Enzymatic Reaction,
Advances in Unconventional Computing 2, 85-104 (2016).

[Summary] Functionality of living organisms is based on decision making. Chemical reactions stand behind information processing in biological systems. Therefore, it is interesting to consider reaction models that show ability to make decisions by evolving towards significantly different states, depending on conditions at which those reactions proceed. It has been recently demonstrated that a system exhibiting cooperative or sigmoidal response with respect to the input exhibits the potential to function as a discriminator of the amplitude or the frequency of its external periodic perturbation. Here we consider a few models of allosteric enzymatic reactions and discuss their applicability for sensing the frequency or the amplitude of the time dependent input in a form of reagent inflow. The output is coded in a product oscillation type. On the basis of numerical simulations we compare results for a full reaction model with its reduced, easier to analyze version

*Hiroshi Noguchi,
Construction of nuclear envelope shape by a high-genus vesicle with pore-size constraint,
Biophysical Journal 111, 824-831 (2016).

[Summary] Nuclear pores have an approximately uniform distribution in the nuclear envelope of most living cells. Hence, the morphology of the nuclear envelope is a spherical stomatocyte with a high genus. We have investigated the morphology of high-genus vesicles under pore-size constraint using dynamically triangulated membrane simulations. Bending-energy minimization without volume or other constraints produces a circular-cage stomatocyte, where the pores are aligned in a circular line on an oblate bud. As the pore radius is reduced, the circular-pore alignment is more stabilized than a random pore distribution on a spherical bud. However, we have clarified the conditions for the formation of a spherical stomatocyte: a small perinuclear volume, osmotic pressure within nucleoplasm, and repulsion between the pores. When area-difference elasticity is taken into account, the formation of cylindrical or budded tubules from the stomatocyte and discoidal stomatocyte is found.

Yuta Tamura and *Yasuyuki Kimura,
Two-dimensional assemblies of nematic colloids in homeotropic cells and their response to electric fields,
Soft Matter 12, 6817-6826 (2016).

[Summary] Micrometer-sized colloidal particles dispersed in nematic liquid crystals interact with each other throughanisotropic interactions induced by orientational deformation of the nematic field. In the case of so-calleddipole nematic colloids, their interaction is of the dipole–dipole type. Two-dimensional, non-close-packedcolloidal assemblies having various characteristics were fabricated using optical tweezers by exploitingthe attraction between anti-parallel dipole nematic colloids in homeotropically aligned nematic cells.Structures comprising polygons, squares, and tetrahedra were built using equal-sized particles, andhexagonal structures were built using particles of two sizes. As the nematic field is sensitive to electricfields, the response of the fabricated assemblies toward an alternating electric field was also studied.All assemblies exhibited homogeneous reversible shrinkage, and their shrinkage rates were dependenton the structure. The maximum shrinkage rate in the linear dimension of the assemblies was over 20%at 5 Vrms for a hexagon comprising tetrahedral units.

Tomo Kurimura, Seori Mori, Masako Miki and *Kenichi Yoshikawa,
Rotary motion of a micro-solid particle under a stationary difference of electric potential,
The Journal of Chemical Physics 145, 034902/1-4 (2016).

[Summary] The periodic rotary motion of spherical sub-millimeter-sized plastic objects is generated under a direct-current electric field in an oil phase containing a small amount of anionic or cationic surfactant. Twin-rotary motion is observed between a pair of counter-electrodes; i.e., two vortices are generated simultaneously, where the line between the centers of rotation lies perpendicular to the line between the tips of the electrodes. Interestingly, this twin rotational motion switches to the reverse direction when an anionic surfactant is replaced by a cationic surfactant. We discuss the mechanism of this self-rotary motion in terms of convective motion in the oil phase where nanometer-sized inverted micelles exist. The reversal of the direction of rotation between anionic and cationic surfactants is attributable to the difference in the charge sign of inverted micelles with surfactants. We show that the essential features in the experimental trends can be reproduced through a simple theoretical model, which supports the validity of the above mechanism.

Irwin Zaid and *Daisuke Mizuno,
Analytical Limit Distributions from Random Power-Law Interactions,
Physical Review Letters 117, 030602 (2016).

[Summary] Nature is full of power-law interactions, e.g., gravity, electrostatics, and hydrodynamics. When sources of such fields are randomly distributed in space, the superposed interaction, which is what we observe, is naively expected to follow a Gauss or Lévy distribution. Here, we present an analytic expression for the actual distributions that converge to novel limits that are in between these already-known limit distributions, depending on physical parameters, such as the concentration of field sources and the size of the probe used to measure the interactions. By comparing with numerical simulations, the origin of non-Gauss and non-Lévy distributions are theoretically articulated.

Soutaro Oda, Yoshitsugu Kubo, Chwen-Yang Shew and *Kenichi Yoshikawa,
Fluctuations induced transition of localization of granular objects caused by degrees of crowding,
Physica D 336, 39-46 (2016).

[Summary] Fluctuations are ubiquitous in both microscopic and macroscopic systems, and an investigation of confined particles under fluctuations is relevant to how living cells on the earth maintain their lives. Inspired by biological cells, we conduct the experiment through a very simple fluctuating system containing one or several large spherical granular particles and multiple smaller ones confined on a cylindrical dish under vertical vibration. We find a universal behavior that large particles preferentially locate in cavity interior due to the fact that large particles are depleted from the cavity wall by small spheres under vertical vibration in the actual experiment. This universal behavior can be understood from the standpoint of entropy

Jerzy Górecki, Jonna N. Gorecka, Bogdan Nowakowski, Hiroshi Ueno and *Kenichi Yoshikawa,
How many enzyme molecules are needed for discrimination oriented applications?,
Physical Chemistry Chemical Physics 18, 20518-20527 (2016).

[Summary] Chemical reactions establish a molecular mechanism for information processing in living organisms. Here we consider a simple enzymatic reaction model that can be used to discriminate parameters characterizing periodic reagent inflow. Numerical simulations based on the kinetic equations show that there exist a range of inflow frequencies and amplitudes in which the time evolution of the system is very sensitive to small changes in the values of these parameters. However, the kinetic equations are derived for the thermodynamic limit, whereas in a real biological medium, like a cell, the number of enzyme molecules is an integer and finite. We use stochastic simulations to estimate discriminator reliability as a function of the number of enzyme molecules involved. For systems with 10000 molecules the functionality predicted by kinetic equations is confirmed. If the number of molecules is decreased to 100, discrimination becomes unreliable

Takuya Hiratsuka, Yuji Takei, Rei Ohmori, Yuuki Imai, Makoto Ozeki, Keiji Tamaki, Hironori Haga, Takashi Nakamura, *Tatsuaki Tsuruyama,
ZFP521 contributes to pre-B-cell lymphomagenesis through modulation of the pre-B-cell receptor signaling pathway,
Oncogene 35, 3227-3238 (2016).

[Summary] ZFP521 was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521 to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521 in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521 was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK, BTK and BANK1 were positively regulated by the ZFP521 gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-myc and c-jun were upregulated following activation of ZFP521. Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-myc and c-jun and of Ccnd3, which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTK and BANK1, targets of ZFP521, suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521, the homolog of ZFP521 in humans, was upregulated. In conclusion, our data showed that the ZFP521 gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

Chika Tongu, Takahiro Kenmotsu, Yuko Yoshikawa, Anatoly A. Zinchenko, Ning Chen and *Kenichi Yoshikawa,
Divalent Cation Shrinks DNA but Inhibits its Compaction with Trivalent Cation,
The Journal of Chemical Physics 144, 205101/1-7 (2016).

[Summary] Our observation reveals the effects of divalent and trivalent cations on the higher-order structure of giant DNA (T4 DNA 166 kbp) by fluorescence microscopy. It was found that divalent cations, Mg(2+) and Ca(2+), inhibit DNA compaction induced by a trivalent cation, spermidine (SPD(3+)). On the other hand, in the absence of SPD(3+), divalent cations cause the shrinkage of DNA. As the control experiment, we have confirmed the minimum effect of monovalent cation, Na(+) on the DNA higher-order structure. We interpret the competition between 2+ and 3+ cations in terms of the change in the translational entropy of the counterions. For the compaction with SPD(3+), we consider the increase in translational entropy due to the ion-exchange of the intrinsic monovalent cations condensing on a highly charged polyelectrolyte, double-stranded DNA, by the 3+ cations. In contrast, the presence of 2+ cation decreases the gain of entropy contribution by the ion-exchange between monovalent and 3+ ions.

Hiroki Sakuta, Nobuyuki Magome, Yoshihito Mori and *Kenichi Yoshikawa,
Negative/Positive Chemotaxis of a Droplet: Dynamic Response to a Stimulant Gas,
Applied Physics Letters 108, 203703/1-4 (2016).

[Summary] We report here the repulsive/attractive motion of an oil droplet floating on an aqueous phase caused by the application of a stimulant gas. A cm-sized droplet of oleic acid is repelled by ammonia vapor. In contrast, a droplet of aniline on an aqueous phase moves toward hydrochloric acid as a stimulant. The mechanisms of these characteristic behaviors of oil droplets are discussed in terms of the spatial gradient of the interfacial tension caused by the stimulant gas.

Kento Yasuda, *Shigeyuki Komura, and Ryuichi Okamoto,
Dynamics of a membrane interacting with an active wall,
Physical Review E 93, 052407/1-12 (2016).

[Summary] We discuss the dynamics of a membrane interacting hydrodynamically with an active wall that exerts random velocities on the ambient fluid. In the case of an active wall, the MSD grows linearly in time in the early stage, which is unusual for a membrane segment. This linear-growth region of the MSD is further extended when the active wall has a finite intrinsic time scale.

*Ryuichi Okamoto, Naofumi Shimokawa, and Shigeyuki Komura,
Nano-domain formation in charged membranes: Beyond the Debye-Huckel approximation,
EPL 114, 28002/1-6 (2016).

[Summary] We investigate the microphase separation in a membrane composed of charged lipids, by taking into account explicitly the electrostatic potential and the ion densities in the surrounding solvent. The static structure factor in the homogeneous state is analytically obtained without using the Debye-Huckel approximation and is found to have a peak at an intermediate wave number. For a binary membrane composed of anionic and neutral lipids, the characteristic wave number corresponds to a scale from several to tens of nanometers.

Shu Hashimoto, Aoi Yoshida, Taeko Ohta, Hiroaki Taniguchi, Koichiro Sadakane and *Kenichi Yoshikawa,
Formation of Stable Cell-Cell Contact without a Solid/Gel Scaffold: Non-invasive Manipulation by Laser under Depletion Interaction with a Polymer,
Chemical Physics Letters 655-656, 11-16 (2016).

[Summary] We report a novel method for constructing a stable three-dimensional cellular assembly in the absence of a solid or gel scaffold. A targeted cell was transferred to another cell, and the two were kept in contact for a few minutes by optical manipulation in an aqueous medium containing a hydrophilic polymer. Interestingly, this cell–cell adhesion was maintained even after elimination of the polymer. We discuss the mechanism of the formation of stable multi-cellular adhesion in terms of spontaneous rearrangement of the components embedded in the pair of facing membranes.

*Hiroshi Noguchi,
Shape deformation of lipid membranes by banana-shaped protein rods: Comparison with isotropic inclusions and membrane rupture,
Physical Review E 93, 052404/1-10 (2016).

[Summary] The assembly of curved protein rods on fluid membranes is studied using implicit-solvent meshless membranesimulations. As the rod curvature increases, the rods on a membrane tube assemble along the azimuthal directionfirst and subsequently along the longitudinal direction. Here, we showthat both transition curvatures decreasewithincreasing rod stiffness. For comparison, curvature-inducing isotropic inclusions are also simulated. When theisotropic inclusions have the same bending rigidity as the other membrane regions, the inclusions are uniformlydistributed on the membrane tubes and vesicles even for large spontaneous curvature of the inclusions. However,the isotropic inclusions with much larger bending rigidity induce shape deformation and are concentrated on theregion of a preferred curvature. For high rod density, high rod stiffness, and/or low line tension of the membraneedge, the rod assembly induces vesicle rupture, resulting in the formation of a high-genus vesicle. A gradualchange in the curvature suppresses this rupture. Hence, large stress, compared to the edge tension, induced bythe rod assembly is the key factor determining rupture. For rod curvature with the opposite sign to the vesiclecurvature, membrane rupture induces inversion of the membrane, leading to division into multiple vesicles aswell as formation of a high-genus vesicle.

*Ryuichi Okamoto, Yuichi Kanemori, Shigeyuki Komura, and Jean-Baptiste Fournier,
Relaxation dynamics of two-component fluid bilayer membranes,
The European Physical Journal E 39, 52/1-21 (2016).

[Summary] We theoretically investigate the relaxation dynamics of a nearly flat binary lipid bilayer membrane by taking into account the membrane tension, hydrodynamics of the surrounding fluid, inter-monolayer friction and mutual diffusion. We find that two relaxation modes associated with the mutual diffusion appear in addition to the three previously discussed relaxation modes reflecting the bending and compression of the membrane.

2017

*Kentaro Suzuki, and Tadashi Sugawara,
Phototaxis of oil droplets comprising a caged fatty acid tightly linked to internal convection,
ChemPhysChem 17, 2300-2303 (2016).

[Summary] We found that novel sub-millimeter-sized photoactive oil droplets of oleic acid bearing a photolabile protecting group, 2-nitrobenzyl oleate (NBO), in basic water exhibited unidirectional motion toward a UV light source. This unidirectional motion can be explained by anisotropic photolysis on a surface of the NBO droplet with low permeability for UV light. Time-dependent changes of the movement under UV irradiation occurred in a cascade manner (still-standing, induction, and active stages). The velocity of the UV-irradiated droplet in the induction stage was small, but it was accelerated sixteen times by the presence of an inner convection structure, which was created by continued photolysis. This characteristic dynamics, which is derived from a supramolecular machinery system towards the external stimulus, may be similar to the phototaxis of a living cell.

2016

*Naofumi Shimokawa, Hiroki Himeno, Tsutomu Hamada, Masahiro Takagi, Shigeyuki Komura, and David Andelman,
Phase diagrams and ordering in charged membranes: Binary mixtures of charged and neutral lipids,
The Journal of Physical Chemistry B 120, 6358-6367 (2016).

[Summary] We propose a model describing the phase behavior of two-component membranes consisting of binary mixtures of electrically charged and neutral lipids. We distinguish between two types of charged membranes: mixtures of charged saturated lipid/neutral unsaturated lipid and a second case of mixtures of neutral saturated lipid/charged unsaturated lipid. The corresponding phase behavior is calculated and shown to be very different.

Takehiro Jimbo, Yuka Sakuma, Naohito Urakami, Primož Ziherl, and *Masayuki Imai,
Role of inverse-Cone-Shape Lipids in Temperature-Controlled Self-Reproduction of Binary Vesicles,
Biophysical Journal 110, 1551-1562 (2016).

[Summary] We investigate a temperature-driven recursive division of binary giant unilamellar vesicles (GUVs). During the heating step of the heating-cooling cycle, the spherical mother vesicle deforms to a budded limiting shape using up the excess area produced by the chain melting of the lipids and then splits off into two daughter vesicles. Upon cooling, the daughter vesicle opens a pore and recovers the spherical shape of the mother vesicle. Our GUVs are composed of DLPE (1,2-dilauroyl-sn-glycero-3-phosphoethanolamine) and DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine). During each cycle, vesicle deformation is monitored by a fast confocal microscope and the images are analyzed to obtain the time evolution of reduced volume and reduced monolayer area difference as the key geometric parameters that quantify vesicle shape. By interpreting the deformationpathway using the area-difference elasticity theory, we conclude that vesicle division relies on (1) a tiny asymmetric distribution of DLPE within the bilayer, which controls the observed deformation from the sphere to the budded shape; and (2) redistribution of DLPE during the deformation-division stage, which ensures that the process is recursive. The spontaneous coupling between membrane curvature and PE lipid distribution is responsible for the observed recursive division of GUVs. These results shed light on the mechanisms of vesicle self-reproduction.

Tomo Kurimura and *Masatoshi Ichikawa,
Noise-supported actuator: Coherent resonance in the oscillations of a micrometersized object under a direct current-voltage,
Applied Physics Letters 108, 144101/1-4 (2016).

[Summary] Noise supported regular motion in a micro-fluidic environment is studied. Recently, it was reported that an aqueous droplet in an oil phase exhibited rhythmic back-and-forth motion under stationary direct current voltage between the cone-shaped electrodes, where the oscillating water droplet moves on a limit cycle orbital. We now confirm that a combination of the limit cycle nature and white noise supports and enhances the regular motion of the object through coherent resonance. The present result will open a way to design an efficient machinery in microfluidic and micromechanical devices.

Shunsuke F. Shimobayashi, Masatoshi Ichikawa and *Takashi Taniguchi,
Direct observations of transition dynamics from macro- to micro-phase separation in asymmetric lipid bilayers induced by externally added glycolipids,
Europhysics Letters 113, Number 5, 56005-p1-p6 (2016).

[Summary] We present the first direct observations of morphological transitions from macro- to micro-phase separation using micrometer-sized asymmetric lipid vesicles exposed to externally added glycolipids (GM1:monosialotetrahexosylganglioside). The transition occurs via an intermediate stripe morphology state. During the transition, monodisperse micro-domains emerge through repeated scission events of the stripe domains. Moreover, we numerically confirmed such transitions using a time-dependent Ginzburg-Landau model, which describes both the intramembrane phase separation and the bending elastic membrane. The experimental and simulation results are in quantitative agreement.

*John J. Molina, Kotaro Otomura, Hayato Shiba, Hideki Kobayashi, Masaki Sano, and Ryoichi Yamamoto,
Rheological evaluation of colloidal dispersions using the smoothed profile method: formulation and applications,
Journal of Fluid Mechanics 792, 590-619 (2016).

[Summary] The smoothed profile method is extended to study the rheological behaviour of colloidal dispersions under shear flow by using the Lees–Edwards boundary conditions. We start with a reformulation of the smoothed profile method, a direct numerical simulation method for colloidal dispersions, so that it can be used with the Lees–Edwards boundary condition, under steady or oscillatory-shear flow. By this reformulation, all the resultant physical quantities, including local and total shear stresses, become available through direct calculation. Three simple rheological simulations are then performed for (1) a spherical particle, (2) a rigid bead chain and (3) a collision of two spherical particles under shear flow. Quantitative validity of these simulations is examined by comparing the viscosity with that obtained from theory and Stokesian dynamics calculations. Finally, we consider the shear-thinning behaviour of concentrated colloidal dispersions.

*Hiroshi Noguchi,
Membrane tubule formation by banana-shaped proteins with or without transient network structure,
Scientific Reports 6, 20935 (2016).

[Summary] In living cells, membrane morphology is regulated by various proteins. Many membrane reshaping proteins contain a Bin/Amphiphysin/Rvs (BAR) domain, which consists of a banana-shaped rod. The BAR domain bends the biomembrane along the rod axis and the features of this anisotropic bending have recently been studied. Here, we report on the role of the BAR protein rods in inducing membrane tubulation, using large-scale coarse-grained simulations. We reveal that a small spontaneous sidecurvature perpendicular to the rod can drastically alter the tubulation dynamics at high protein density, whereas no significant difference is obtained at low density. A percolated network is intermediately formed depending on the side curvature. This network suppresses tubule protrusion, leading to the slow formation of fewer tubules. Thus, the side curvature, which is generated by protein–protein andmembrane–protein interactions, plays a significant role in tubulation dynamics. We also find that positive surface tensions and the vesicle membrane curvature can stabilize this network structure by suppressing the tubulation.

Atsuji Kodama, Yuka Sakuma, *Masayuki Imai, Yutaka Oya, Toshihiro Kawakatsu, Nicolas Puff, and Miglena I. Angelova,
Migration of phospholipid vesicles in response to OH- stimuli,
Soft Matter 12, 2877-2886 (2016).

[Summary] We demonstrate migration of phospholipid vesicles in response to a pH gradient. Upon simple microinjectionof a NaOH solution, the vesicles linearly moved to the tip of the micro-pipette and the migration velocity was proportional to the gradient of OH concentration. Vesicle migration was characteristic of OH ions and no migration was observed for monovalent salts or nonionic sucrosesolutions. The migration of vesicles is quantitatively described by the surface tension gradient modelwhere the hydrolysis of the phospholipids by NaOH solution decreases the surface tension of the vesicle. The vesicles move toward a direction where the surface energy decreases. Thus the chemical modification of lipids produces a mechanical force to drive vesicles.

Hayato Shiba, Hiroshi Noguchi, and *Jean-Baptiste Fournier,
Monte Carlo study of the frame, fluctuation and internal tensions of fluctuating membranes with fixed area,
Soft Matter 12, 2373-2380 (2016).

[Summary] Three types of surface tensions can be defined for lipid membranes: the internal tension, σ, conjugated to the real membrane area in the Hamiltonian, the mechanical frame tension, τ, con- jugated to the projected area, and the “fluctuation tension”, r, obtained from the fluctuation spec- trum of the membrane height. We investigate these surface tensions by means of a Monge gauge lattice Monte Carlo simulation involving the exact, nonlinear, Helfrich Hamiltonian and a measure correction for excess entropy of the Monge gauge. Our results for the relation between σ and τ agrees well with the theoretical prediction of [J.-B. Fournier and C. Barbetta, Phys. Rev. Lett., 2008, 100, 078103] based on a Gaussian approximation. This provides a valuable knowledge of τ in the standard Gaussian models where the tension is controlled by σ. However, contrary to the conjecture in the above paper, we find that r exhibits no significant difference from τ over more than five decades of tension. Our results appear to be valid in the thermodynamic limit and are robust to changing the ensemble in which the membrane area is controlled.

Yuki Oda, Koichiro Sadakane, Yuko Yoshikawa, Tadayuki Imanaka, Kingo Takiguchi, Masahito Hayashi, Takahiro Kenmotsu and *Kenichi Yoshikawa,
Highly Concentrated Ethanol Solution Behaves as a Good Solvent for DNA as Revealed by Single-Molecule Observation,
ChemPhysChem 17(4), 471-473 (2016).

Array

Yukinori Nishigami, *Hiroaki Ito, Seiji Sonobe, and *Masatoshi Ichikawa,
Non-periodic oscillatory deformation of an actomyosin microdroplet encapsulated within a lipid interface,
Scientific Reports 6, 18964/1-11 (2016).

[Summary] Active force generation in living organisms, which is mainly involved in actin cytoskeleton and myosin molecular motors, plays a crucial role in various biological processes. Although the contractile properties of actomyosin have been extensively investigated, their dynamic contribution to a deformable membrane remains unclear because of the cellular complexities and the difficulties associated with in vitro reconstitution. Here, by overcoming these experimental difficulties, we demonstrate the dynamic deformation of a reconstituted lipid interface coupled with self-organized structure of contractile actomyosin. Therein, the lipid interface repeatedly oscillates without any remarkable periods. The oscillatory deformation of the interface is caused by the aster-like three-dimensional hierarchical structure of actomyosin inside the droplet, which is revealed that the oscillation occurs stochastically as a Poisson process.

Yuta Tamura and *Yasuyuki Kimura,
Fabrication of ring assemblies of nematic colloids and their electric response,
Applied Physics Letters 108, 011903 (2016).

[Summary] Colloidal particles with a limited number of interactive sites are called colloidal molecules, andtheir assemblies have been intensively studied to reveal complex micro-structures. In this study, weexamine colloidal particles in nematic liquid crystals, so-called nematic colloids, as colloidal moleculesand fabricated some non-close-packed assemblies. Micrometer-sized particles with homeotropicsurface anchoring of liquid crystal in a homeotropic cell interact with each other throughdipolar-type anisotropic interactions arising from the elastic deformation of the nematic fieldaround the particles. Using optical tweezers, we have built two-dimensional colloidal assemblieswith low packing densities, including polygon-rings, chains of polygon-rings, and lattices composedof octagon-rings in a hierarchical way from smaller structure units. Because the nematic fieldis sensitive to the electric field, the response of the polygon-rings to an alternative electric field hasbeen studied. They exhibited homogeneous reversible shrink as large as 15%–22% to their originalsizes under several volts.

2015

*Hiroshi Noguchi,
Shape transitions of high-genus fluid vesicles,
EPL 112, 58004/1-6 (2015).

[Summary] The morphologies of genus-2 to -8 fluid vesicles are studied by using dynamically triangulated membrane simulations with area-difference elasticity. It is revealed that the alignments of the membrane pores alter the vesicle shapes and the types of shape transitions for the genus-3 or higher genus. At a high reduced volume, a stomatocyte with a circular alignment of g + 1 pores continuously transforms into a discocyte with a line of g pores with increasing intrinsic area difference. In contrast, at a low volume, a stomatocyte transforms into a (g+1)-hedral shape and subsequently exhibits a discrete phase transition to a discocyte.

*Hiroaki Ito, Yukinori Nishigami, Seiji Sonobe, and *Masatoshi Ichikawa,
Wrinkling of a spherical lipid interface induced by actomyosin cortex,
Physical Review E 92, 062711/1-8 (2015).

[Summary] Actomyosin actively generates contractile forces that provide the plasma membrane with the deformation stresses essential to carry out biological processes. Although the contractile property of purified actomyosin has been extensively studied, to understand the physical contribution of the actomyosin contractile force on a deformable membrane is still a challenging problem and of great interest in the field of biophysics. Here, we reconstitute a model system with a cell-sized deformable interface that exhibits anomalous curvature-dependent wrinkling caused by the actomyosin cortex underneath the spherical closed interface. Through a shape analysis of the wrinkling deformation, we find that the dominant contributor to the wrinkled shape changes from bending elasticity to stretching elasticity of the reconstituted cortex upon increasing the droplet curvature radius of the order of the cell size, i.e., tens of micrometers. The observed curvature dependence is explained by the theoretical description of the cortex elasticity and contractility. Our present results provide a fundamental insight into the deformation of a curved membrane induced by the actomyosin cortex.

Takuma Hoshino, Shigeyuki Komura, and David Andelman,
Correlated lateral phase separations in stacks of lipid membranes,
Journal of Chemical Physics 143, 243124/1-9 (2015).

[Summary] Motivated by the experimental study of Tayebi et al. [Nature Mater. 11, 1074 (2012)] on phase separation of stacked multi-component lipid bilayers, we propose a model composed of stacked two-dimensional Ising spins. We study both its static and dynamical features using Monte Carlo simulations with Kawasaki spin exchange dynamics that conserves the order parameter. We show that at thermodynamical equilibrium, due to strong inter-layer correlations, the system forms a continuous columnar structure for any finite interaction across adjacent layers. Furthermore, the phase separation shows a faster dynamics as the inter-layer interaction is increased. This temporal behavior is mainly due to an effective deeper temperature quench because of the larger value of the critical temperature, Tc, for larger inter-layer interaction. When the temperature ratio, T/Tc, is kept fixed, the temporal growth exponent does not increase and even slightly decreases as function of the increased inter-layer interaction.

Tomohiro Yanao, Sosuke Sano and *Kenichi Yoshikawa,
Chiral selection in wrapping, crossover, and braiding of DNA mediated by asymmetric bend-writhe elasticity,
AIMS Biophysics 2(4), 666–694 (2015).

[Summary] Wrapping, crossover, and braiding of DNA are the motifs of fundamental interest ingenome packaging, gene regulation, and enzyme recognition. This study explores elasticmechanisms for the selection of chirality in wrapping, crossover, and braiding of DNA based on acoarse-grained model. The DNA model consists of two elastic chains that mutually intertwine in aright-handed manner forming a double-stranded helix with the distinction between major and minorgrooves. Although individual potential energy functions of the DNA model have no asymmetry interms of left and right twist, the model as a whole exhibits an asymmetric propensity to writhe in theleft direction upon bending due to the right-handed helical geometry. Monte Carlo simulations of thismodel suggest that DNA has a propensity to prefer left-handed wrapping around a spherical coreparticle and also around a uniform rod due to the asymmetric elastic coupling between bending andwrithing. This result indicates an elastic origin of the uniform left-handed wrapping of DNA innucleosomes and also has implications on the wrapping of double-stranded DNA around rod-likemolecules. Monte Carlo simulations of the DNA model also suggest that two juxtaposed DNAmolecules can braid each other spontaneously under moderate attractive interactions with thepreference for left-handed braiding due to the asymmetric coupling between bending and writhing.This result suggests the importance of asymmetric elasticity in the selection of chirality in braidingof a pair of DNA molecules.

Hiroshi Ueno, Tatsuaki Tsuruyama, Bogdan Nowakowski, Jerzy Górecki, and *Kenichi Yoshikawa,
Discrimination of time-dependent inflow properties with a cooperative dynamical system.,
Chaos 25, 103115 (2015).

[Summary] Many physical, chemical, and biological systems exhibit a cooperative or sigmoidal response with respect to the input. In biochemistry, such behavior is called an allosteric effect. Here, we demonstrate that a system with such properties can be used to discriminate the amplitude or frequency of an external periodic perturbation. Numerical simulations performed for a model sigmoidal kinetics illustrate that there exists a narrow range of frequencies and amplitudes within which the system evolves toward significantly different states. Therefore, observation of system evolution should provide information about the characteristics of the perturbation. The discrimination properties for periodic perturbation are generic. They can be observed in various dynamical systems and for different types of periodic perturbation.

Tatsuaki Tsuruyama, Wulamujiang Aini, Takuya Hiratsuka,
Reassessment of H&E-stained clot specimens and immunohistochemistry of phosphorylated Stat5 for histologic diagnosis of MDS/MPN.,
Pathology 47, 673-7 (2015).

[Summary] Few studies have comprehensively analysed histopathological findings of bone marrow clots for diagnosis of haematopoietic cell dysplasia. In particular, a limited number of studies have assessed the use of haematoxylin and eosin (H&E) staining, which is generally considered less informative than May-Giemsa staining. In the current study, the utility of bone marrow clot specimens for diagnosis was examined using H&E staining and immunohistochemistry. Patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN), including chronic myelomonocytic leukaemia (CMML), atypical chronic myeloid leukaemia (aCML) lacking Philadelphia chromosome, and juvenile myelomonocytic leukaemia (JMML), were selected for histological evaluation. H&E stained specimens were advantageous for observation of atypical basophilic staining of the cytoplasm and nucleus related to dysplasia. This finding was significantly supported for both MDS and MDS/MPN (p < 0.05 versus May-Giemsa staining); therefore, we concluded that H&E staining could be used for identification of dysplastic cells. In addition, despite the loss of tissue structure, phosphorylated Stat5 immunostaining was sufficiently useful for the observation of myelodysplastic blasts. Thus, clot specimens are useful for diagnosis of haematopoietic dysplasia by pathologists.

Masanobu Tanaka, Marcel Hörning, Hiroyuki Kitahata and *Kenichi Yoshikawa,
Elimination of a spiral wave pinned at an obstacle by a train of plane waves: Effect of diffusion between obstacles and surrounding media,
Chaos 25, 103127 (2015).

[Summary] In excitable media such as cardiac tissue and Belousov-Zhabotinsky reaction medium, spiral waves tend to anchor (pin) to local heterogeneities. In general, such pinned waves are difficult to eliminate and may progress to spatio-temporal chaos. Heterogeneities can be classified as either the absence or presence of diffusive interaction with the surrounding medium. In this study, we investigated the difference in the unpinning of spiral waves from obstacles with and without diffusive interaction, and found a profound difference. The pacing period required for unpinning at fixed obstacle size is larger in case of diffusive obstacles. Further, we deduced a generic theoretical framework that can predict the minimal unpinning period. Our results explain the difference in pacing periods between for the obstacles with and without diffusive interaction, and the difference is interpreted in terms of the local decrease of spiral wave velocity close to the obstacle boundary caused in the case of diffusive interaction.

*Shigeyuki Komura, Kento Yasuda, and Ryuichi Okamoto,
Dynamics of two-component membranes surrounded by viscoelastic media,
Journal of Physics: Condensed Matter 27, 432001/1-7 (2015).

[Summary] We discuss the dynamics of two-component fluid membranes which are surrounded by viscoelastic media. We assume that membrane-embedded proteins can diffuse laterally and induce a local membrane curvature. The mean squared displacement of a tagged membrane segment is obtained as a generalized Einstein relation. When the elasticity of the surrounding media obeys a power-law behavior in frequency, an anomalous diffusion of the membrane segment is predicted. We also consider the situation where the proteins generate active non-equilibrium forces. The generalized Einstein relation is further modified by an effective temperature that depends on the force dipole energy. The obtained generalized Einstein relations are useful for membrane microrheology experiments.

*Hiroshi Noguchi,
Formation of polyhedral vesicles and polygonal membrane tubes induced by banana-shaped proteins,
Journal of Chemical Physics 143, 243109/1-7 (2015).

[Summary] The shape transformations of fluid membranes induced by curved protein rods are studied using meshless membrane simulations. The rod assembly at low rod density induces a flat membrane tube and oblate vesicle. It is found that the polyhedral shapes are stabilized at high rod densities.The discrete shape transition between triangular and buckled discoidal tubes is obtained and their curvature energies are analyzed by a simple geometric model. For vesicles, triangular hosohedron and elliptic-disk shapes are formed in equilibrium, whereas tetrahedral and triangular prism shapes are obtained as metastable states.

Kensuke Kurihara, Yusaku Okura, Muneyuki Matsuo, Taro Toyota, Kentaro Suzuki, and *Tadashi Sugawara,
A recursive vesicle-based model protocell with a primitive model cell cycle,
Nature Communications 6, 8352 (2015).

[Summary] Self-organized lipid structures (protocells) have been proposed as an intermediate between nonliving material and cellular life. Synthetic production of model protocells can demonstrate the potential processes by which living cells first arose. While we have previously described a giant vesicle (GV)-based model protocell in which amplification of DNA was linked to self-reproduction, the ability of a protocell to recursively self-proliferate for multiple generations has not been demonstrated. Here we show that newborn daughter GVs can be restored to the status of their parental GVs by pH-induced vesicular fusion of daughter GVs with conveyer GVs filled with depleted substrates. We describe a primitive model cell cycle comprising four discrete phases (ingestion, replication, maturity and division), each of which is selectively activated by a specific external stimulus. The production of recursive self-proliferating model protocells represents a step towards eventual production of model protocells that are able to mimic evolution.

Shogo Okubo, Shuhei Shibata, Yuriko Sasa Kawamura, Masatoshi Ichikawa and *Yasuyuki Kimura,
Dynamic clustering of driven colloidal particles on a circular path,
Physical Review E 92, 032303 (2015).

[Summary] We studied the collective motion of particles forced to move along a circular path in water by utilizing anoptical vortex. Their collective motion, including the spontaneous formation of clusters and their dissociation,was observed. The observed temporal patterns depend on the number of particles on the path and the variationof their sizes. The addition of particles with different sizes suppresses the dynamic formation and dissociation ofclusters and promotes the formation of specific stationary clusters. These experimental findings are reproducedby numerical simulations that take into account the hydrodynamic interaction between the particles and the radialtrapping force confining the particles to the circular path. A transition between stationary and nonstationaryclustering of the particles was observed by varying their size ratio in the binary-size systems. Our simulationreveals that the transition can be either continuous or discontinuous depending on the number of different-sizeparticles. This result suggests that the size distribution of particles has a significant effect on the collectivebehavior of self-propelled particles in viscous fluids.

Shogo Okubo, Shuhei Shibata, Yuriko Sasa Kawamura, Masatoshi Ichikawa and *Yasuyuki Kimura,
Dynamic clustering of driven colloidal particles on a circular path,
Physical Review E 92, 032303 (2015).

[Summary] We studied the collective motion of particles forced to move along a circular path in water by utilizing anoptical vortex. Their collective motion, including the spontaneous formation of clusters and their dissociation,was observed. The observed temporal patterns depend on the number of particles on the path and the variationof their sizes. The addition of particles with different sizes suppresses the dynamic formation and dissociation ofclusters and promotes the formation of specific stationary clusters. These experimental findings are reproducedby numerical simulations that take into account the hydrodynamic interaction between the particles and the radialtrapping force confining the particles to the circular path. A transition between stationary and nonstationaryclustering of the particles was observed by varying their size ratio in the binary-size systems. Our simulationreveals that the transition can be either continuous or discontinuous depending on the number of different-sizeparticles. This result suggests that the size distribution of particles has a significant effect on the collectivebehavior of self-propelled particles in viscous fluids.

Naohito Urakami, Akio Takai, Masayuki Imai and Takashi Yamamoto,
Molecular dynamics simulation for shape change of water-in-oil droplets,
Molecular Simulation 41, 986-992 (2015).

[Summary] We performed molecular dynamics (MD) simulations of water-in-oil droplet shape transformations induced by the addition of polymer chains. In a prior experiment, transformations of spherical droplets to rod-like, worm-like and network-like droplets were observed. In our previous study, we reproduced rod-like droplets via coarse-grained MD simulations, and the mechanism for the droplet shape change was elucidated by considering the contact area between the chains and the surfactant head groups. However, in that simulation model, we could not reproduce the worm-like and network-like droplets. In this study, we improved the simulation model. For a small number of chains, several spherical droplets were obtained. As the number of chains increased, the spherical droplets were transformed to rod-like, worm-like and networklikeshapes by coalescence of the droplets. The calculated and experimental results agreed well, and we verified that themechanism for the droplet shape transformations observed in the present simulations could be explained by the mechanism suggested in the previous study.

Yue Ma, Naoki Ogawa, Yuko Yoshikawa, Toshiaki Mori, Tadayuki Imanaka, Yoshiaki Watanabe and *Kenichi Yoshikawa,
Protective Effect of Ascorbic Acid against Double-strand Breaks in Giant DNA: Marked Differences among the Damage Induced by Photo-irradiation, Gamma-rays and Ultrasound,
Chemical Physics Letters 638, 205-209 (2015).

[Summary] tThe protective effect of ascorbic acid against double-strand breaks in DNA was evaluated by single-molecule observation of giant DNA (T4 DNA; 166 kbp) through fluorescence microscopy. Samples wereexposed to three different forms of radiation: visible light, -ray and ultrasound. With regard to irradiationwith visible light, 1 mM AA reduced the damage down to ca. 30%. Same concentration of AA decreased thedamage done by -ray to ca. 70%. However, AA had almost no protective effect against the damage causedby ultrasound. This significant difference is discussed in relation to the physico-chemical mechanism ofdouble-strand breaks depending on the radiation source.

Yongjun Chen, Kosuke Suzuki and *Kenichi Yoshikawa,
Self-organized Target and Spiral Patterns through the “Coffee Ring” Effect,
Journal of Chemical Physics 143, 084702 (2015).

[Summary] We studied the precipitation pattern of fullerene C60 nanocrystals generated through the evaporation of a confined liquid bridge. In contrast to the usual “coffee ring” pattern, both target and spiral patterns were observed. The characteristics of the pattern critically depended on the concentration of the solution, the temperature, and the level of vacuum. In addition, the morphology of the microscopic precipitates varied greatly as a function of these experimental parameters. This pattern formation can be interpreted as a two-step rhythmic nucleation/precipitation of fullerene crystals during receding motion of the contact line. Symmetric motion of the contact line produces a target pattern, and the propagation of distortion of the liquid interface caused by a disturbance generates a spiral pattern.

Naoki Umezawa, Yuhei Horai, Yuki Imamura, Makoto Kawakubo, Mariko Nakahira, Nobuki Kato, Akira Muramatsu, Yuko Yoshikawa, *Kenichi Yoshikawa and Tsunehiko Higuchi,
Structurally Diverse Polyamines: Solid-Phase Synthesis and Interaction with DNA,
ChemBioChem 16, 1811-1819 (2015).

[Summary] A versatile solid-phase approach based on peptide chemistry was used to construct four classes of structurally diverse polyamines with modified backbones: linear, partially constrained, branched, and cyclic. Their effects on DNA duplex stability and structure were examined. The polyamines showed distinct activities, thus highlighting the importance of polyamine backbone structure. Interestingly, the rank order of polyamine ability for DNA compaction was different to that for their effects on circular dichroism and melting temperature, thus indicating that these polyamines have distinct effects on secondary and higher-order structures of DNA.

Xiaojun Ma, Tomohiro Aoki, Tatsuaki Tsuruyama, and Shuh Narumiya,
Definition of prostaglandin E2-EP2 signals in the colon tumor microenvironment which amplify inflammation and tumor growth.,
Cancer Reserach 75, 2822-32 (2015).

[Summary] Inflammation in the colon contributes significantly to colorectal cancer development. While aspirin reduces the colorectal cancer risk, its action mechanism, especially in inflammation in tumor microenvironment, still remains obscure. Here, we examined this issue by subjecting mice deficient in each prostaglandin (PG) receptor to colitis-associated cancer model. Deficiency of PGE receptor subtype EP2 selectively reduced, and deficiency of EP1 and EP3 enhanced, the tumor formation. EP2 is expressed in infiltrating neutrophils and tumor-associated fibroblasts in stroma, where it regulates expression of inflammation- and growth-related genes in a self-amplification manner. Notably, expression of cytokines such as TNFα and IL6, a chemokine, CXCL1, a PG-producing enzyme, COX-2, and Wnt5A was significantly elevated in tumor lesions of wild-type mice but this elevation was significantly suppressed in EP2-deficient mice. Intriguingly, EP2 stimulation in cultured neutrophils amplified expression of TNFα, IL6, CXCL1, COX-2, and other proinflammatory genes synergistically with TNFα, and EP2 stimulation in cultured fibroblasts induced expression of EP2 itself, COX-2, IL6, and Wnt genes. EP2 expression in infiltrating neutrophils and tumor-associated fibroblasts was also found in clinical specimen of ulcerative colitis-associated colorectal cancer. Bone marrow transfer experiments suggest that EP2 in both cell populations is critical for tumorigenesis. Finally, administration of a selective EP2 antagonist potently suppressed tumorigenesis in this model. Our study has thus revealed that EP2 in neutrophils and tumor-associated fibroblasts promotes colon tumorigenesis by amplifying inflammation and shaping tumor microenvironment, and suggests that EP2 antagonists are promising candidates of aspirin-alternative for chemoprevention of colorectal cancer.

Hisako Takigawa-Imamura, Ritsuko Morita, Takafumi Iwaki, Takashi Tsuji and *Kenichi Yoshikawa,
Tooth germ invagination from cell–cell interaction: Working hypothesis on mechanical instability,
Journal of Theoretical Biology 382, 284 (2015).

[Summary] In the early stage of tooth germ development, the bud of the dental epithelium is invaginated by the underlying mesenchyme, resulting in the formation of a cap-like folded shape. This bud-to-cap transition plays a critical role in determining the steric design of the tooth. The epithelial-mesenchymal interaction within a tooth germ is essential for mediating the bud-to-cap transition. Here, we present a theoretical model to describe the autonomous process of the morphological transition, in which we introduce mechanical interactions among cells. Based on our observations, we assumed that peripheral cells of the dental epithelium bound tightly to each other to form an elastic sheet, and mesenchymal cells that covered the tooth germ would restrict its growth. By considering the time-dependent growth of cells, we were able to numerically show that the epithelium within the tooth germ buckled spontaneously, which is reminiscent of the cap-stage form. The difference in growth rates between the peripheral and interior parts of the dental epithelium, together with the steric size of the tooth germ, were determining factors for the number of invaginations. Our theoretical results provide a new hypothesis to explain the histological features of the tooth germ.

Daigo Yamamoto, Tsuyoshi Takada, Masashi Tachibana, Yuta Iijima, Akihisa Shioi and Kenichi Yoshikawa,
Micromotors working in water through artificialaerobic metabolism,
Nanoscale 7, 13186–13190 (2015).

[Summary] Most catalytic micro/nanomotors that have been developed so far use hydrogen peroxide as fuel, while some use hydrazine. These fuels are difficult to apply because they can cause skin irritation, and often form and store disruptive bubbles. In this paper, we demonstrate a novel catalytic Pt micromotor that does not produce bubbles, and is driven by the oxidation of stable, non-toxic primary alcohols and aldehydes with dissolved oxygen. This use of organic oxidation mirrors living systems, and lends this new motor essentially the same characteristics, including decreased motility in low oxygen environments and the direct isothermal conversion of chemical energy into mechanical energy. Interestingly, the motility direction is reversed by replacing the reducing fuels with hydrogen peroxide. Therefore, these micromotors not only provide a novel system in nanotechnology, but also help in further revealing the underlining mechanisms of motility of living organisms.

Keita Ikari, Yuka Sakuma, Takehiro Jimbo, Atsuji Kodama, *Masayuki Imai, Pierre-Alain Monnard, and Steen Rasmussen,
Dynamics of fatty acid vesicles in response to pH stimuli,
Soft Matter 11, 6327-6334 (2015).

[Summary] We investigate the dynamics of decanoic acid/decanoate (DA) vesicles in response to pH stimuli. Twotypes of dynamic processes induced by the micro-injection of NaOH solutions are sequentiallyobserved: deformations and topological transitions. In the deformation stage, DA vesicles show a seriesof shape deformations, i.e., prolate–oblate–stomatocyte-sphere. In the topological transition stage,spherical DA vesicles follow either of the two pathways, pore formation and vesicle fusion. The pHstimuli modify a critical aggregation concentration of DA molecules, which causes the solubilization ofDA molecules in the outer leaflet of the vesicle bilayers. This solubilization decreases the outer surfacearea of the vesicle, thereby increasing surface tension. A kinetic model based on area differenceelasticity theory can accurately describe the dynamics of DA vesicles triggered by pH stimuli.

*Tsutomu Hamada, Rie Fujimoto, Shunsuke F. Shimobayashi, Masatoshi Ichikawa, *Masahiro Takagi,
Molecular behavior of DNA in a cell-sized compartment coated by lipids,
Physical Review E 91, 62717 (2015).

[Summary] The behavior of long DNA molecules in a cell-sized confined space was investigated. Microscopic observation revealed that the adsorption of coiled DNA onto the membrane surface depended on the size of the vesicular space.

Masa Tsuchiya, Alessandro Giuliani, Midori Hashimoto, Jekaterina Erenpreisa and Kenichi Yoshikawa,
Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line,
PLOS ONE 10(6), e0128565 (2015).

[Summary] BackgroundThe underlying mechanism of dynamic control of the genome-wide expression is a fundamental issue in bioscience. We addressed it in terms of phase transition by a systemic approach based on both density analysis and characteristics of temporal fluctuation for the time-course mRNA expression in differentiating MCF-7 breast cancer cells.MethodologyIn a recent work, we suggested criticality as an essential aspect of dynamic control of genome-wide gene expression. Criticality was evident by a unimodal-bimodal transition through flattened unimodal expression profile. The flatness on the transition suggests the existence of a critical transition at which up- and down-regulated expression is balanced. Mean field (averaging) behavior of mRNAs based on the temporal expression changes reveals a sandpile type of transition in the flattened profile. Furthermore, around the transition, a self-similar unimodal-bimodal transition of the whole expression occurs in the density profile of an ensemble of mRNA expression. These singular and scaling behaviors identify the transition as the expression phase transition driven by self-organized criticality (SOC).Principal FindingsEmergent properties of SOC through a mean field approach are revealed: i) SOC, as a form of genomic phase transition, consolidates distinct critical states of expression, ii) Coupling of coherent stochastic oscillations between critical states on different time-scales gives rise to SOC, and iii) Specific gene clusters (barcode genes) ranging in size from kbp to Mbp reveal similar SOC to genome-wide mRNA expression and ON-OFF synchronization to critical states. This suggests that the cooperative gene regulation of topological genome sub-units is mediated by the coherent phase transitions of megadomain-scaled conformations between compact and swollen chromatin states.Conclusion and SignificanceIn summary, our study provides not only a systemic method to demonstrate SOC in whole-genome expression, but also introduces novel, physically grounded concepts for a breakthrough in the study of biological regulation.

Hiroaki Ito, Navina Kuss, Bastian E. Rapp, Masatoshi Ichikawa, Thomas Gutsmann, Klaus Brandenburg, Johannes M. B. Pöschl, and *Motomu Tanaka,
Quantification of the Influence of Endotoxins on the Mechanics of Adult and Neonatal Red Blood Cells,
Journal of Physical Chemistry B 119, 7837−7845 (2015).

[Summary] In this study, we physically modeled the influence of endotoxin-induced sepsis symptoms on human red blood cells (RBCs) by quantifying the impact of endotoxins on the cell mechanics by the analysis of Fourier-transformed mean square amplitude of shape fluctuation, called flicker spectroscopy. With the aid of a microfluidic diffusion chamber, we noninvasively determined principal mechanical parameters of human RBCs in the absence and presence of endotoxins for individual RBCs for the first time. Because of the elongation of saccharide chain length of endotoxins, we found an increase in the morphological transition from discocytes to echinocytes, and monotonic changes in the mechanical parameters. Since septic shocks often cause lethal risks of neonates, we measured the mechanical parameters of neonatal RBCs, and compared them to those of adult RBCs. The quantitative comparison reveals that neonatal RBCs are more susceptible to the effect of endotoxins than adult RBCs. Furthermore, coincubation with the antiseptic peptide P19-2.5 (Aspidasept) with endotoxin results in a slight suppression of the impact of the endotoxin. The strategy proposed in our study can potentially be applied for the quantitative diagnosis of RBCs based on mechanical readouts.

Daigo Yamamoto, Chika Nakajima, Akihisa Shioi, Marie Pierre Krafft, Kenichi Yoshikawa ,
The evolution of spatial ordering of oil drops fast spreading on a water surface,
Nature Communications 6, 7189/1-6 (2015).

[Summary] The design of dynamically self-assembled systems is of high interest in science and technology. Here, we report a unique cascade in the self-ordering of droplets accompanied by a dewetting transition. The dynamic self-emergent droplets are observed when a thin liquid layer of an immiscible fluorocarbon oil (perfluorooctyl bromide, PFOB) is placed on a water surface. Due to the gradual evaporation of PFOB, a circular PFOB-free domain appears as a result of a local dewetting transition. A circular pearling structure is generated at the rim with the growth of the dewetting hole. As the next stage, linear arrays of droplets are generated in a radial manner from the centre of the hole. These one-dimensional arrangements then evolve into two-dimensional hexagonal arrays of microdroplets through collective rhythmical shrinking/expanding motions. The emergence of such dynamic patterns is discussed in terms of the nonlinear kinetics of the dewetting transition under thermodynamically dissipative conditions.

Yongjun Chen, Shun N. Watanabe and *Kenichi Yoshikawa,
Roughening Dynamics of Radial Imbibition in a Porous Medium,
Journal of Physical Chemistry C 199(22), 12508–12513 (2015).

[Summary] We report radial imbibition of water in a porous medium in a Hele–Shaw cell, including forced imbibition and spontaneous imbibition. Washburn’s law is confirmed in our experiment. Radial imbibition follows scaling dynamics. For forced radial imbibition, anomalous roughening dynamics is found when the front invades the porous medium, and the roughening dynamics depend on the flow rate of the injected fluid. The growth exponents increase linearly with an increase in the flow rate while the roughness exponents decrease with an increase in the flow rate. For spontaneous imbibition, we found a growth exponent (β = 0.6) that was independent of the pressure applied at the liquid inlet, and the roughness exponent decreased with an increase in pressure. Thus, it has become evident that the roughening dynamics of radial imbibition is markedly different from one-dimensional imbibition with a planar interface window.

Yoshitsugu Kubo, *Shio Inagaki, *Masatoshi Ichikawa, and Kenichi Yoshikawa,
Mode bifurcation of a bouncing dumbbell with chirality,
Physical Review E 91, 052905/1-9 (2015).

[Summary] We studied the behavior of a dumbbell bouncing upon a sinusoidally vibrating plate. By introducing chiral asymmetry to the geometry of the dumbbell, we observed a cascade of bifurcations with an increase in the vibration amplitude: spinning, orbital, and rolling. In contrast, for an achiral dumbbell, bifurcation is generated by a change from random motion to vectorial inchworm motion. A simple model particle was considered in a numerical simulation that reproduced the essential aspects of the experimental observation. The mode bifurcation from directional motion to random motion is interpreted analytically by a simple mechanical discussion.

*Takafumi Iwaki, Tomomi Ishido, Ken Hirano, Alexei Lazutin, Valentina V. Vasilevskaya, Takahiro Kenmotsu and Kenichi Yoshikawa,
Marked difference in conformational fluctuation between giant DNA molecules in circular and linear forms,
Journal of Chemical Physics 142, 145101 (2015).

[Summary] We performed monomolecular observations on linear and circular giant DNAs (208 kbp) in an aqueous solution by the use of fluorescence microscopy. The results showed that the degree of conformational fluctuation in circular DNA was ca. 40% less than that in linear DNA, although the long-axis length of circular DNA was only 10% smaller than that of linear DNA. Additionally, the relaxation time of a circular chain was shorter than that of a linear chain by at least one order of magnitude. The essential features of this marked difference between linear and circular DNAs were reproduced by numerical simulations on a ribbon-like macromolecule as a coarse-grained model of a long semiflexible, double-helical DNA molecule. In addition, we calculated the radius of gyration of an interacting chain in a circular form on the basis of the mean field model, which provides a better understanding of the present experimental trend than a traditional theoretical equation.

*Yoshiyuki Kageyama, Tomonori Ikegami, Natsuko Hiramatsu, *Sadamu Takeda, and Tadashi Sugawara,
Structure and growth behavior of centimeter-sized helical oleate assemblies formed with assistance of medium-length carboxylic acids,
Soft Matter 11, 3550-3558 (2015).

[Summary] The nonequilibrium organization of self-assemblies from small building-block molecules offers an attractive and essential means to develop advanced functional materials and to understand the intrinsic nature of life systems. Fatty acids are well-known amphiphiles that form self-assemblies of several shapes. Here, we found that the lengths of helical structures of oleic acid formed in a buffered aqueous solution are dramatically different by the presence or absence of certain amphiphilic carboxylic acids. For example, under the coexistence of a small amount of N-decanoyl-L-alanine, we observed the formation of over 1 centimeter-long helical assemblies of oleate with a regular pitch and radius, whereas mainly less than 100 μm-long helices formed without this additive. Such long helical assemblies are unique in terms of their highly dimensional helical structure and growth dynamics. Results from the real-time observation of self-assembly formation, site-selective small-angle X-ray scattering, high-performance liquid chromatography analysis, and pH titration experiments suggested that the coexisting carboxylates assist in elongation by supplying oleate molecules to a scaffold for oleate helical assembly.

Masahiro Mizuno, Taro Toyota, Miki Konishi, Yoshiyuki Kageyama, *Masumi Yamada, and Minoru Seki,
Formation of monodisperse hierarchical lipid particles utilizing microfluidic droplets in a non-equilibrium state,
Langmuir 31, 2334-2341 (2015).

Kanta Tsumoto, Masafumi Arai, Naoki Nakatani, Shun N. Watanabe and *Kenichi Yoshikawa,
Does DNA Exert an Active Role in Generating Cell-Sized Spheres in an Aqueous Solution with a Crowding Binary Polymer?,
Life 5(1), 459-466 (2015).

[Summary] We report the spontaneous generation of a cell-like morphology in an environment crowded with the polymers dextran and polyethylene glycol (PEG) in the presence of DNA. DNA molecules were selectively located in the interior of dextran-rich micro-droplets, when the composition of an aqueous two-phase system (ATPS) was near the critical condition of phase-segregation. The resulting micro-droplets could be controlled by the use of optical tweezers. As an example of laser manipulation, the dynamic fusion of two droplets is reported, which resembles the process of cell division in time-reverse. A hypothetical scenario for the emergence of a primitive cell with DNA is briefly discussed.

Koh M. Nakagawa and *Hiroshi Noguchi,
Morphological changes of amphiphilic molecular assemblies induced by chemical reactions,
Soft Matter 11, 1403-1411 (2015).

[Summary] Shape transformations of amphiphilic molecular assemblies induced by chemical reactions are studied using coarse-grained molecular simulations. A binding reaction between hydrophilic and hydrophobic molecules is considered. It is found that the reaction induces transformation of an oil droplet to a tubular vesicle via bicelles and vesicles with discoidal arms. The discoidal arms close into vesicles, which are subsequently fused into the tubular vesicle. Under the chemical reaction, the bicelle-to-vesicle transition occurs at smaller sizes than in the absence of the hydrophobic molecules. It is revealed that the enhancement of this transition is due to embedded hydrophobic particles that reduce the membrane bending rigidity.

Takahiro Umeki, Masahiko Ohata, *Hiizu Nakanishi, Masatoshi Ichikawa,
Dynamics of microdroplets over the surface of hot water,
Scientific Reports 5, 8046/1-6 (2015).

[Summary] When drinking a cup of coffee under the morning sunshine, you may notice white membranes of steam floating on the surface of the hot water. They stay notably close to the surface and appear to almost stick to it. Although the membranes whiffle because of the air flow of rising steam, peculiarly fast splitting events occasionally occur. They resemble cracking to open slits approximately 1 mm wide in the membranes, and leave curious patterns. We studied this phenomenon using a microscope with a high-speed video camera and found intriguing details: i) the white membranes consist of fairly monodispersed small droplets of the order of 10 μm; ii) they levitate above the water surface by 10 ~ 100 μm; iii) the splitting events are a collective disappearance of the droplets, which propagates as a wave front of the surface wave with a speed of 1 ~ 2 m/s; and iv) these events are triggered by a surface disturbance, which results from the disappearance of a single droplet.

Jean Wolff, *Shigeyuki Komura, and David Andelman,
Budding of domains in mixed bilayer membranes,
Physical Review E 91, 012708/1-10 (2015).

[Summary] We propose a model that accounts for the budding behavior of domains in lipid bilayers, where each of the bilayer leaflets has a coupling between its local curvature and the local lipid composition. The compositional asymmetry between the two monolayers leads to an overall spontaneous curvature. The membrane free energy contains three contributions: the bending energy, the line tension, and a Landau free energy for a lateral phase separation.Within amean-field treatment, we obtain various phase diagrams which contain fully budded, dimpled, and flat states. In particular, for some range of membrane parameters, the phase diagrams exhibit a tricritical behavior as well as a three-phase coexistence region. The global phase diagrams can be divided into three types and are analyzed in terms of the curvature-composition coupling parameter and domain size.

Kingo Takiguchi, Makiko Egishi, Yohko Tanaka-Takiguchi, Masahito Hayashi and Kenichi Yoshikawa,
Specific Transformation of Assembly with Actin Filaments and Molecular Motors in a Cell-Sized Self-Emerged Liposome,
Origins of Life and Evolution of Biospheres 44(4), 325-329 (2015).

[Summary] Eukaryotes, by the same combination of cytoskeleton and molecular motor, for example actin filament and myosin, can generate a variety of movements. For this diversity, the organization of biological machineries caused by the confinement and/or crowding effects of internal living cells, may play very important roles.

Anatoly A. Zinchenko and *Kenichi Yoshikawa,
Compaction of Double-Stranded DNA by Negatively Charged Proteins and Colloids,
Current Opinion in Colloid & Interface Science 20, 60-65 (2015).

[Summary] A great number of past in vivo and in vitro studies on DNA condensation/compaction made clear DNA conformational behavior and its influence on DNA bioactivity in systems containing either polymers or colloids which are positively charged or electrically neutral. However, there still remains a lack of understanding about interaction between DNA and like-charged species. Such knowledge is important for deeper insight into DNA behavior in cellular environment, where DNA encounters negatively charged biopolymers such as RNA and RNase at relatively high concentrations, and should contribute to an overall understanding of the intrinsic mechanism that underlies the spatiotemporal dynamics of biomacromolecules in various cellular processes. In this review, we focus on DNA condensation/compaction by negatively-charged species, compare it with established earlier model systems of DNA condensation/compaction, and discuss recent advances in the field. We show that DNA compaction by negatively charged polymers and colloids exhibits some similarities with that induced by neutral polymers, but stress that several new features imposed by the electrostatics of polyanions should be considered to grasp the whole picture.

*Hiroshi Noguchi, Ai Sakashita, and Masayuki Imai,
Shape transformations of toroidal vesicles,
Soft Matter 11, 193-201 (2015).

[Summary] Morphologies of genus-1 and 2 toroidal vesicles are studied numerically by dynamically triangulated membrane models and experimentally by confocal laser microscopy. Our simulation results reproduce shape transformations observed in our experiments well. At large reduced volumes of the genus-1vesicles, obtained vesicle shapes agree with the previous theoretical prediction, in which axisymmetric shapes are assumed: double-necked stomatocyte, discoidal toroid, and circular toroid. However, for small reduced volumes, it is revealed that a non-axisymmetric discoidal toroid and handled discocyte exist in thermal equilibrium in the parameter range, in which the previous theory predicts axisymmetric discoidal shapes. Polygonal toroidal vesicles and subsequent budding transitions are also found. The entropy caused by shape fluctuations slightly modifies the stability of the vesicle shapes.

*Hiroshi Noguchi, Ai Sakashita and Masayuki Imai,
Shape transformations of toroidal vesicles,
Soft Matter 11, 193-201 (2015).

[Summary] Morphologies of genus-1 and 2 toroidal vesicles are studied numerically by dynamically triangulatedmembrane models and experimentally by confocal laser microscopy. Our simulation results reproduceshape transformations observed in our experiments well. At large reduced volumes of the genus-1vesicles, obtained vesicle shapes agree with the previous theoretical prediction, in which axisymmetricshapes are assumed: double-necked stomatocyte, discoidal toroid, and circular toroid. However, forsmall reduced volumes, it is revealed that a non-axisymmetric discoidal toroid and handled discocyteexist in thermal equilibrium in the parameter range, in which the previous theory predicts axisymmetricdiscoidal shapes. Polygonal toroidal vesicles and subsequent budding transitions are also found. Theentropy caused by shape fluctuations slightly modifies the stability of the vesicle shapes.

*Chwen-Yang Shew and Kenichi Yoshikawa,
A toy model for nucleus-sized crowding confinement,
Journal of Physics: Condensed Matter 27(6), 064118/1-7 (2015).

[Summary] We conduct Monte Carlo simulations to understand the spatial distribution of a polymer molecule confined within a rigid spherical capsule under crowding conditions, via a bead-spring chain model. To adjust the crowding level, the polymer is mixed with spherical crowders. As the interior of the capsule becomes more crowded, chain monomers tend to move to the capsule boundary under the penalty of conformational entropy. By incorporating some attraction between monomers and crowders, the polymer chain moves away from the capsule boundary. The interplay, between the conformational entropy, DNA-protein interaction, and molecular crowding induced depletion force between the chain and capsule boundary, may be essential to elucidate the heterogeneous chromatin structure in nuclei. Furthermore, the effects of chain length and size disparity between the monomers and the crowders are also investigated preliminarily.

*Shio Inagaki, Hiroyuki Ebata and Kenichi Yoshikawa,
Steadily oscillating axial bands of binary granules in a nearly filled coaxial cylinder,
Physical Review E 91, 010201(R)/1-5 (2015).

[Summary] Granular materials often segregate under mechanical agitation such as flowing, shaking, or rotating, in contrast to an expectation of mixing. It is well known that bidisperse mixtures of granular materials in a partially filled rotating cylinder exhibit monotonic coarsening dynamics of segregation. Here we report the steady oscillation of segregated axial bands under the stationary rotation of a nearly filled coaxial cylinder for O(10 3 ) revolutions. The axial bands demonstrate steady back-and-forth motion along the axis of rotation. Experimental findings indicated that these axial band dynamics are driven by global convection throughout the system. The essential features of the spatiotemporal dynamics are reproduced with a simple phenomenological equation that incorporates the effect of global convection.

2014

Yuka Takeuchi, Yoko Sugawara, Tadashi Sugawara, and *Masakazu Iwasaka,
Magnetic rotation of monosodium urate and urinary tract stones for clinical treatment applications,
Magnetics, IEEE Transactions on 50, 6101204 (2014).

[Summary] In recent years, diseases such as gout and urinary tract calculi, caused by crystals in vivo, are rapidly increasing due to excess intake of alcohol, salt, and so forth. Crystals causing gout are compounds of uric acid with sodium in the blood, which are called monosodium urate (MSU) crystals. On the other hand, urinary tract calculus is caused by calcium oxalate crystal. In this paper, we focused on the behaviors of MSU crystals and oxalic acid crystals under magnetic fields of several hundreds of mT (Tesla), and developed a method for new medical treatments by using a magnetic field. MSU crystals and oxalic acid crystals were prepared by a recrystallization from the aqueous solution. We observed these crystals using a charge-coupled device microscope under horizontal magnetic fields (maximum of 500 mT). While the magnetic fields were applied, the MSU crystals were oriented by the magnetic fields. In addition, oxalic acid crystals were oriented perpendicularly to the magnetic field. The dynamic rotation of MSU crystal was observed quantitatively by measuring the time course of the lightscattering intensities of the MSU suspension. The results show that the diamagnetic anisotropy in the MSU crystals controlled the rotational responses. As a possible medical application, a remote control of the MSU crystals and oxalic acid crystals in living body by the magnetic fields is proposed.

Yuri Mizukawa, Kentaro Suzuki, Shigefumi Yamamura, Yoko Sugawara, Tadashi Sugawara, and *Masakazu Iwasaka,
Magnetic manipulation of nucleic acid base microcrystals for DNA sensing,
Magnetics, IEEE Transactions on 50, 5001904 (2014).

[Summary] This paper develops a magneto-DNA sensing device composed of a crystalline nucleic acid base, which is a component of DNA on the basis of the dynamic rotation due to its diamagnetic anisotropy under a magnetic field of the mT order. As a basic study, recrystallized nucleic acid bases, such as cytosine, adenine, and guanine, were used for the measurement. We focused on the induced dynamic orientation effect on the nucleic acid base crystals by exposure of the magnetic field at 0.5 T. The morphologically long axis of a cytosine crystal oriented parallel to the applied magnetic fields, while those of adenine and guanine oriented perpendicular to the magnetic field. As a next stage, we traced the angular difference of the magnetic rotation of DNA adhered to guanine crystals comparing the rotation angles of the pre-exposure sample and the during exposure sample with and without DNA. It was revealed that the degree of the magnetic rotation of guanine crystals with DNA was seemingly less than that of guanine crystals without DNA. The difference in angle of the magnetic rotation of the guanine crystal may allow to detect the adhesion of DNA. The method obtained by detecting precise magnetic rotation of nucleic acid base crystals can be applied to the manipulation and sensing of macromolecules in dispersion containing nucleic acid bases, such as DNA and RNA.

*Hiroshi Noguchi,
Two- or three-step assembly of banana-shaped proteins coupled with shape transformation of lipid membranes,
EPL 108, 48001/1-6 (2014).

[Summary] BAR superfamily proteins have a banana-shaped domain that causes the local bending of lipid membranes. We study as to how such a local anisotropic curvature induces effectiveinteraction between proteins and changes the global shape of vesicles and membrane tubes using meshless membrane simulations. Our study reveals that the rods assemble via two continuous directional phase separations unlike a conventional two-dimensional phase separation. As the rod curvature increases, in the membrane tube the rods assemble along the azimuthal direction and subsequently along the longitudinal direction accompanied by shape transformation of the tube. In the vesicle, in addition to these two assembly processes, further increase in the rod curvature induces tubular scaffold formation.

Hiroki Himeno, Naofumi Shimokawa, Shigeyuki Komura, David Andelman, *Tsutomu Hamada, and Masahiro Takagi,
Charge-induced phase separation in lipid membranes,
Soft Matter 10, 7959-7967 (2014).

[Summary] Phase separation in lipid bilayers that include negatively charged lipids is examined experimentally. We observed phase-separated structures and determined the membrane miscibility temperatures in several binary and ternary lipid mixtures of unsaturated neutral lipid, dioleoylphosphatidylcholine (DOPC), saturated neutral lipid, dipalmitoylphosphatidylcholine (DPPC), unsaturated charged lipid, dioleoylphosphatidylglycerol (DOPG(−)), saturated charged lipid, dipalmitoylphosphatidylglycerol (DPPG(−)), and cholesterol. In binary mixtures of saturated and unsaturated charged lipids, the combination of the charged head with the saturation of the hydrocarbon tail is a dominant factor in the stability of membrane phase separation. DPPG(−) enhances phase separation, while DOPG(−) suppresses it. Furthermore, the addition of DPPG(−) to a binary mixture of DPPC/cholesterol induces phase separation between DPPG(−)-rich and cholesterol-rich phases. This indicates that cholesterol localization depends strongly on the electric charge on the hydrophilic head group rather than on the ordering of the hydrocarbon tails. Finally, when DPPG(−) was added to a neutral ternary system of DOPC/DPPC/cholesterol (a conventional model of membrane rafts), a three-phase coexistence was produced. We conclude by discussing some qualitative features of the phase behaviour in charged membranes using a free energy approach.

*Shunsuke F. Shimobayashi and *Masatoshi Ichikawa,
Emergence of DNA-Encapsulating Liposomes from a DNA-Lipid Blend Film,
Journal of Physical Chemistry B 118, 10688-10694 (2014).

[Summary] Spontaneous generation of DNA-enclosing liposomes from a DNA−lipid blend film is investigated. The special properties of the lipid vesicles, namely, micrometer size, unilamellarity, and dense polymer encapsulation acquired by the dehydration−rehydration process, are physicochemically revealed. We found that the formation of giant unilamellar vesicles encapsulating DNAs are governed by micropatterns of the films, such as dots and network patterns. From the results, we proposed a plausible physical mechanism for the dehydration−rehydration process, making it possible to optimize the encapsulation of any agent.

Fumi Takabatake, Kenichi Yoshikawa, and *Masatoshi Ichikawa,
Communication: Mode bifurcation of droplet motion under stationary laser irradiation,
The Journal of Chemical Physics 141, 051103/1-4 (2014).

[Summary] The self-propelled motion of a mm-sized oil droplet floating on water, induced by a local temperature gradient generated by CW laser irradiation is reported. The circular droplet exhibits two types of regular periodic motion, reciprocal and circular, around the laser spot under suitable laser power. With an increase in laser power, a mode bifurcation from rectilinear reciprocal motion to circular motion is caused. The essential aspects of this mode bifurcation are discussed in terms of spontaneous symmetry-breaking under temperature-induced interfacial instability, and are theoretically reproduced with simple coupled differential equations.

*Tatsuaki Tsuruyama,
A model of cell biological signaling predicts the phase transition of signaling and provides mathematical formula of signaling,
PLOS ONE 9, e102911 (2014).

[Summary] A biological signal is transmitted by interactions between signaling molecules in the cell. To date, there have been extensive studies regarding signaling pathways using numerical simulation of kinetic equations that are based on equations of continuity and Fick's law. To obtain a mathematical formulation of cell signaling, we propose a stability kinetic model of cell biological signaling of a simple two-parameter model based on the kinetics of the diffusion-limiting step. In the present model, the signaling is regulated by the binding of a cofactor, such as ATP. Non-linearity of the kinetics is given by the diffusion fluctuation in the interaction between signaling molecules, which is different from previous works that hypothesized autocatalytic reactions. Numerical simulations showed the presence of a critical concentration of the cofactor beyond which the cell signaling molecule concentration is altered in a chaos-like oscillation with frequency, which is similar to a discontinuous phase transition in physics. Notably, we found that the frequency is given by the logarithm function of the difference of the outside cofactor concentration from the critical concentration. This implies that the outside alteration of the cofactor concentration is transformed into the oscillatory alteration of cell inner signaling. Further, mathematical stability kinetic analysis predicted a discontinuous dynamic phase transition in the critical state at which the cofactor concentration is equivalent to the critical concentration. In conclusion, the present model illustrates a unique feature of cell signaling, and the stability analysis may provide an analytical framework of the cell signaling system and a novel formulation of biological signaling.

*Shuji Fujii, Shigeyuki Komura, and Chun-Yi David Lu,
Structural rheology of the smectic phase,
Materials 7, 5146-5168 (2014).

[Summary] In this review article, we discuss the rheological properties of the thermotropic smectic liquid crystal 8CB with focal conic domains (FCDs) from the viewpoint of structural rheology. It is known that the unbinding of the dislocation loops in the smectic phase drives the smectic-nematic transition. Here we discuss how the unbinding of the dislocation loops affects the evolution of the FCD size, linear and nonlinear rheological behaviors of the smectic phase. By studying the FCD formation from the perpendicularly oriented smectic layers, we also argue that dislocations play a key role in the structural development in layered systems. Furthermore, similarities in the rheological behavior between the FCDs in the smectic phase and the onion structures in the lyotropic lamellar phase suggest that these systems share a common physical origin for the elasticity.

*Shigeyuki Komura and David Andelman,
Physical aspects of heterogeneities in multi-component lipid membranes,
Advances in Colloid and Interface Science 208, 34-46 (2014).

[Summary] Ever since the raft model for biomembranes has been proposed, the traditional view of biomembranes based on the fluid-mosaic model has been altered. In the raft model, dynamical heterogeneities in multi-component lipid bilayers play an essential role. Focusing on the lateral phase separation of biomembranes and vesicles, we review some of the most relevant research conducted over the last decade. We mainly refer to those experimental works that are based on physical chemistry approach, and to theoretical explanations given in terms of soft matter physics. In the first part, we describe the phase behavior and the conformation of multi-component lipid bilayers. After formulating the hydrodynamics of fluid membranes in the presence of the surrounding solvent, we discuss the domain growth-law and decay rate of concentration fluctuations. Finally, we review several attempts to describe membrane rafts as two-dimensional microemulsion.

Tomohiro Yanao and *Kenichi Yoshikawa,
Chiral symmetry breaking of a double-stranded helical chain through bend-writhe coupling,
Physical Review E 89, 062713/1-16 (2014).

[Summary] This paper explores asymmetric elasticity of a double-stranded helical chain, which serves as a minimal model of biopolymers. The model consists of two elastic chains that mutually intertwine in a right-handed manner, forming a double-stranded helix. A simple numerical experiment for structural relaxation, which reduces the total elastic energy of the model monotonically without thermal fluctuations, reveals possible asymmetric elasticity inherent in the helical chain. It is first shown that a short segment of the double-stranded helical chain has a tendency to unwind when it is bent. It is also shown that a short segment of the helical chain has a tendency to writhe in the left direction upon bending. This tendency gives rise to a propensity for a longer segment of the chain to form a left-handed superhelix spontaneously upon bending. Finally, this propensity of the helical chain to form a left-handed superhelix is proposed to be a possible origin of the uniform left-handed wrapping of DNA around nucleosome core particles in nature. The results presented here could provide deeper insights into the roles and significance of helical chirality of biopolymers.

Yutaka Sumino and *Kenichi Yoshikawa,
Amoeba-like motion of an oil droplet Chemical model of self-motile organisms,
The European Physical Journal Special Topics 223, 1345–1352 (2014).

[Summary] In this paper, we demonstrate our recent attempt to construct a chemical model system of amoeboid motion. The system is intended to mimic biological motility based on the generation and collapse of an elastic aggregate; it is composed of oil, water, and surfactants. In this chemical system, the oil–water interface shows extension and retreat of spherical extrusions accompanied by the generation of aggregate on the interface. This instability of the oil–water interface can cause autonomous splitting and motion of a floating oil droplet. The current mathematical model based on the generation of a passive elastic gel is explained, as well as the discrepancy between the model and the experiments. We further describe recently observed microscopic characteristics of the aggregate formation process that might cause the interfacial instability. Finally, we discuss the disadvantage of a chemical model system compared with active colloid and in vitro biological systems, and also mention its potential advantages.

Kentaro Takahashi and Yasuyuki Kimura,
Dynamics of colloidal particles in electrohydrodynamic convection of nematic liquid crystal,
Physical Review E 90, 012502/1-5 (2014).

[Summary] We have studied the dynamics of micrometer-sized colloidal particles in electrohydrodynamic convection of nematic liquid crystal. Above the onset voltage of electroconvection, the parallel array of convection rolls appears to be perpendicular to the nematic field at first. The particles are forced to rotate by convection flow and are trapped within a single roll in this voltage regime. The frequency of rotational motion increases with the applied voltage. Under a much larger voltage where the roll axis temporally fluctuates, the particles occasionally hop to the neighbor rolls. The motion perpendicular to the roll axis exhibits diffusion behavior at a long time period. The effective diffusion constant is 10^3–10^4 times larger than the molecular one. The observed behavior is compared with the result obtained by a simple stochastic model for the transport of the particles in convection. The enhancement of diffusion can be quantitatively described well by the rotation frequency in a roll, the width of the roll, and the hopping probability to the neighbor rolls.

*Shuji Fujii, Shigeyuki Komura, and C.-Y. David Lu,
Structural rheology of focal conic domains: a stress-quench experiment,
Soft Matter 10, 5289-5295 (2014).

[Summary] We study the dynamics of focal conic domain (FCD) formation in a thermotropic smectic phase under shear stress. It is known that increasing the shear stress induces a non-equilibrium phase transition from a smectic phase with FCDs (SmAI) to another smectic phase (SmAII) in which the layers are oriented. By quenching the shear stress from the SmAII phase to the SmAI phase, we find three characteristic modes in the FCD formation process. The first mode is attributed to the edge dislocation dynamics induced by climb motions. The second mode results from FCD formation. The first and second modes show slowing down close to the smectic–nematic transition temperature, implying that the dynamics are dominated by dislocation unbinding. The third mode originates from the alignment of FCDs which form oily streaks. Such an alignment occurs when the shear stress balances the line tension of the oily streaks.

Masa Tsuchiya, Midori Hashimoto, Yoshiko Takenaka, Ikuko N. Motoike and *Kenichi Yoshikawa,
Global Genetic Response in a Cancer Cell: Self-Organized Coherent Expression Dynamics,
PLOS ONE 9(8), e105491 (2014).

[Summary] Understanding the basic mechanism of the spatio-temporal self-control of genome-wide gene expression engaged with the complex epigenetic molecular assembly is one of major challenges in current biological science. In this study, the genomewide dynamical profile of gene expression was analyzed for MCF-7 breast cancer cells induced by two distinct ErbB receptor ligands: epidermal growth factor (EGF) and heregulin (HRG), which drive cell proliferation and differentiation, respectively. We focused our attention to elucidate how global genetic responses emerge and to decipher what is an underlying principle for dynamic self-control of genome-wide gene expression. The whole mRNA expression was classified into about a hundred groups according to the root mean square fluctuation (rmsf). These expression groups showed characteristic time-dependent correlations, indicating the existence of collective behaviors on the ensemble of genes with respect to mRNA expression and also to temporal changes in expression. All-or-none responses were observed for HRG and EGF (biphasic statistics) at around 10–20 min. The emergence of time-dependent collective behaviors of expression occurred through bifurcation of a coherent expression state (CES). In the ensemble of mRNA expression, the self-organized CESs reveals distinct characteristic expression domains for biphasic statistics, which exhibits notably the presence of criticality in the expression profile as a route for genomic transition. In time-dependent changes in the expression domains, the dynamics of CES reveals that the temporal development of the characteristic domains is characterized as autonomous bistable switch, which exhibits dynamic criticality (the temporal development of criticality) in the genome-wide coherent expression dynamics. It is expected that elucidation of the biophysical origin for such critical behavior sheds light on the underlying mechanism of the control of whole genome.

Sayuri Tanaka, Yuma Oki, and Yasuyuki Kimura*,
Melting process of a single finite-sized two-dimensional colloidal crystal,
Physical Review E 89, 052305/1-9 (2014).

[Summary] We have studied the melting process of a finite-sized two-dimensional colloidal crystal by video microscopy. The local area fraction φ and the local hexatic orientational order parameter ψ6 have been evaluated for respective Voronoi cells in the crystal. The histogram of φ exhibits a peak and the peak φ continuously decreases with the time elapsed. The histogram of |ψ6| shows an abrupt broadening for φ < 0.65. This critical value of φ is the transition point between the hexatic and dense liquid phases in finite crystal. We have also evaluated φ and|ψ6| as a function of the distance from the center of the crystal r. φ(r) is almost constant within the crystal and monotonously decreases with the time elapsed. |ψ6(r)| gradually decreases with r but there is the core with |ψ6|=1 at earlier time stage. We have also studied the melting of a finite-sized crystal composed of soft-core particles by Brownian dynamics simulation and verified the finite-size effect on the melting process. The simulated behavior is qualitatively in good agreement with the experimental results.

David A. Head, Emi Ikebe, Akiko Nakamasu, Peijuan Zhang, Lara Gay Villaruz, Suguru Kinoshita, Shoji Ando, and *Daisuke Mizuno,
High-frequency affine mechanics and nonaffine relaxation in a model cytoskeleton,
Physical Review E 89, 042711/1-5 (2014).

[Summary] The cytoskeleton is a network of crosslinked, semiflexible filaments, and it has been suggested that it has properties of a glassy state. Here we employ optical-trap-based microrheology to apply forces to a modelcytoskeleton and measure the high-bandwidth response at an anterior point. Simulating the highly nonlinear andanisotropic stress-strain propagation assuming affinity, we found that theoretical predictions for the quasistaticresponse of semiflexible polymers are only realized at high frequencies inaccessible to conventional rheometers.We give a theoretical basis for determining the frequency when both affinity and quasistaticity are valid, and we discuss with experimental evidence that the relaxations at lower frequencies can be characterized by the experimentally obtained nonaffinity parameter.

Ai Sakashita, Masayuki Imai, and *Hiroshi Noguchi,
Morphological variation of lipid vesicle confined in spherical vesicle,
Physical Review E 89, 040701(R)/1-4 (2014).

[Summary] Morphologies of a double-bilayer vesicle were explored experimentally by fast confocal laser microscopy and numerically by a dynamically triangulated membrane model with area-difference elasticity. The confinement was found to induce several shapes of the inner vesicles that had not been observed in unilamellar vesicles: double and quadruple stomatocytes, slit vesicle, and vesicles of two or three compartments with various shapes. The simulations reproduced the experimental results very well and some of the shape transitions can be understood by a simple theoretical model for axisymmetric shapes.

Ai Sakashita, Masayuki Imai, and *Hiroshi Noguchi,
Morphological variation of a lipid vesicle confined in a spherical vesicle,
Physical Review E 89, 040701/1-4 (2014).

[Summary] Morphologies of a double-bilayer vesicle were explored experimentally by fast confocal laser microscopy andnumerically by a dynamically triangulated membrane model with area-difference elasticity. The confinement wasfound to induce several shapes of the inner vesicles that had not been observed in unilamellar vesicles: doubleand quadruple stomatocytes, slit vesicle, and vesicles of two or three compartments with various shapes. Thesimulations reproduced the experimental results very well and some of the shape transitions can be understoodby a simple theoretical model for axisymmetric shapes.

*Tomoyuki Mochida, Yusuke Funasako, Kousuke Takazawa, Masashi Takahashi, Michio M. Matsushita, and Tadashi Sugawara,
Chemical control of the monovalent-divalent electron-transfer phase transition in biferrocenium-TCNQ salts,
Chemical Communications 50, 5473-5475 (2014).

[Summary] An ionic molecular crystal of (1',1'''-dineopentylbiferrocene)(F1TCNQ)3 exhibits a first-order phase transition from a monovalent state (D+A3) to a divalent state (D2+A32−) at around 120 K. The transition was successfully controlled by modulation of the redox potentials using FnTCNQ (n = 0-2) and by chemical-pressure effects.successfully controlled by modulation of the redox potentials using FnTCNQ (n = 0–2) and by chemical-pressure effects.

*Kazuhiko Seki, Saurabh Mogre, and Shigeyuki Komura,
Diffusion coefficients in leaflets of bilayer membranes,
Physical Review E 89, 022713/1-12 (2014).

[Summary] We study diffusion coefficients of liquid domains by explicitly taking into account the two-layered structure called leaflets of the bilayer membrane. In general, the velocity fields associated with each leaflet are different and the layers sliding past each other cause frictional coupling. We obtain analytical results of diffusion coefficients for a circular liquid domain in a leaflet, and quantitatively study their dependence on the inter-leaflet friction. We also show that the diffusion coefficients diverge in the absence of coupling between the bilayer and solvents, even when the inter-leaflet friction is taken into account. In order to corroborate our theory, the effect of the inter-leaflet friction on the correlated diffusion is examined.

*Anatoly A. Zinchenko, Kanta Tsumoto, Shizuaki Murata and Kenichi Yoshikawa,
Crowding by Anionic Nanoparticles Causes DNA Double-Strand Instability and Compaction,
The Journal of Physical Chemistry B 118, 1256-1262 (2014).

[Summary] Up to the present, DNA structural transitions caused by cationic polymers as well as in concentrated solutions of neutral polymers are well documented, while a little is known about DNA interaction with like-charge species. Herein, changes in the structure of DNA induced by anionic nanoparticles of different sizes (20–130 nm) were investigated by combining single-molecule DNA fluorescent microscopy, to monitor the conformational dynamics of long-chain DNA, with spectroscopic methods, to gain insight into changes in the secondary structure of DNA. The results showed that several percent of negatively charged silica nanoparticles induced DNA compaction from a coil to a globule, and this change was accompanied by a decrease in the melting temperature of the DNA double helix. DNA was compacted into toroidal condensates with reduced diameters of about 20–30 nm. Smaller 20 nm nanoparticles triggered a DNA coil–globule transition at lower concentrations, but the exclusion volume for each type of nanoparticle at the point of complete DNA collapse, as estimated by taking into account the depth of the ionic atmosphere, was found to be almost the same.

*Chwen-Yang Shew, Kenta Kondo and Kenichi Yoshikawa,
Rigidity of a spherical capsule switches the localization of encapsulated particles between inner and peripheral regions under crowding condition: Simple model on cellular architecture,
The Journal of Chemical Physics 140, 024907/1-9 (2014).

[Summary] We have investigated the inhomogeneous interior of confined spherical cavities as capsules containingencapsulated binary hard sphere mixtures for different compositions and cavity wall rigidity. Such a greatly simplified model manifests the effects of macromolecular crowding arising from excluded volume interactions in a tiny cell or a cellular nucleus. By fixing the number of large particles, the level of crowding is adjusted by changing the amount of small hard spheres in the cavity. For a rigid cavity, large spheres tend to pack in liquid-like order apart from the surface to the center of the cavity as the crowding level is increased. Whereas, for a soft cavity, larger spheres tend to blend with small spheres in the peripheral region at near the boundary of the cavity, and are susceptible to be depleted from the interior of the cavity as the cavity becomes more crowded. These results may help future elucidation of the thermodynamic pathways to stabilize the inhomogeneous structure ofmixtures confined in cavities, such as the derepression of genome materials around the interior rim of the nucleus in a cancerous cell.

Rastko Joksimovic, Shun N. Watanabe, Sven Riemer, Michael Gradzielski and *Kenichi Yoshikawa,
Self-organized patterning through thedynamic segregation of DNA and silicananoparticles,
Scientific Reports 4, 3660/1-7 (2014).

[Summary] Exotic pattern formation as a result of drying of an aqueous solution containing DNA and silicananoparticles is reported. The pattern due to segregation was found to critically depend on the relative ratioof nanoparticles and DNA, as revealed by polarization microscopy, scanning electron microscopy, andfluorescence microscopy. The blurred radial pattern that is usually observed in the drying of a colloidalsolution was shown to be vividly sharpened in the presence of DNA. Uniquely curved, crescent-shapedmicrometer-scale domains are generated in regions that are rich in nanoparticles. The characteristicsegregated patterns observed in the present study are interpreted in terms of a large aspect ratio between thepersistence length (~50 nm) and the diameter (~2 nm) of double-stranded DNA, and the relatively smallsilica nanoparticles (radius: 5 nm).

*Katsuto Takakura, Takahiko Yamamoto, Kensuke Kurihara, Taro Toytota, Kiyoshi Ohnuma, and *Tadashi Sugawara,
Spontaneous Transformation from Micelles to Vesicles Associated with Sequential Conversionsof Comprising Amphiphiles within Assemblies,
Chemical Communications 50, 2190-2192 (2014).

[Summary] A morphological transformation from hybrid micelles to giant vesicles was observed in aqueous dispersion associated with formation of a double-chained amphiphile as a result of themigration of dodecylamine from the amphiphilic imine to the amphiphilic aldehyde within the hydrophobic environment of amphiphilic aggregates.

2013

Fumihiko Kono, Tetsuya Honda, Aini Wulamujiang, Hironori Haga, *Tatsuaki Tsuruyama,
IFN-γ/CCR5 expression in invariant NKT cells and CCL5 expression in capillary veins of dermal papillae correlate with development of psoriasis vulgaris,
British Journal of Dermatology, in press (2013).

[Summary] There have been extensive studies regarding which types of T lymphocytes are involved in psoriasis vulgaris (PV). However, it has remained unclear as to which types of T lymphocytes may directly contribute to psoriasiform epidermal and vascular hyperplasia.To understand the role of TCRVα24+ invariant natural killer T (iNKT) in the development of PV, a total of 17 patients with were enrolled in this study. In the present study, using biopsy samples of PV plaques, TCRVα24+ invariant natural killer T (iNKT) cells were investigated regarding cytokine production to understand their roles in development of disease.The number of IFN-γ+ iNKT cells correlated with the length of the psoriasiform hyperplasia rete ridge and the psoriasis area and severity index (PASI). IFN-γ+ iNKT cells in psoriatic skin exhibited higher C-C chemokine receptor type 5 (CCR5) expression, and the amount of C-C chemokine ligand 5 (CCL5), a ligand for CCR5, was increased in capillary veins of psoriasis plaques. CCR5+ iNKT cell numbers significantly correlated with the number of capillary vein endothelial cells expressing CCL5 in PV. Furthermore, the number of CCL5+ capillary veins correlated with the maximal rete ridge length.CONCLUSIONS:IFN-γ/CCR5 expression in iNKT cells and CCL5 expression in dermal papillae vessels of dermal papillae are correlated with the development of psoriasiform hyperplasia and microabscess. We propose that these iNKT cells may become useful targets for development of novel therapeutic approaches to PV. This article is protected by copyright. All rights reserved.

Yu Kakimoto, Shinji Ito, Hitoshi Abiru, Hirokazu Kotani, Munetaka Ozeki, Keiji Tamaki, Tatsuaki Tsuruyama*,
Sorbin and SH3 domain-containing protein 2 is released from infarcted heart in the very early phase: proteomic analysis of cardiac tissues from patients,
Journal of American Heart Association 2, e000565 (2013).

[Summary] We applied a novel proteomic approach to formalin-fixed, paraffin-embedded human tissue and aimed to reveal the molecular changes in the very early phase of acute myocardial infarction. Heart tissue samples were collected from 5 patients who died within 7 hours of myocardial infarction and from 5 age- and sex-matched control cases. Infarcted and control myocardia were histopathologically diagnosed and captured using laser microdissection. Proteins were extracted using an originally established method and analyzed using liquid chromatography-tandem mass spectrometry. The label-free quantification demonstrated that the levels of 21 proteins differed significantly between patients and controls. In addition to known biomarkers, the sarcoplasmic protein sorbin and SH3 domain-containing protein 2 (SORBS2) was greatly reduced in infarcted myocardia. Immunohistochemical analysis of cardiac tissues confirmed the decrease, and Western blot analysis showed a significant increase in serum sorbin and SH3 domain-containing protein 2 in acute myocardial infarction patients (n=10) compared with control cases (n=11).Our advanced comprehensive analysis using patient tissues and serums indicated that sarcoplasmic sorbin and SH3 domain-containing protein 2 is released from damaged cardiac tissue into the bloodstream upon lethal acute myocardial infarction.

Kuniyoshi Izaki and *Yasuyuki Kimura,
Hydrodynamic effects in the measurement of interparticle forces in nematic colloids,
Physical Review E 88, 54501 (2013).

[Summary] We propose improved measurement methods of interparticle force between nematic colloids. Although variousmethods have been utilized for the force measurement, the comparison between the forces obtained by differentmethods has not been reported. In the frequently used method called the “free-release” method, the hydrodynamicinteraction between moving particles has a serious influence on the measurement. In this study we modifiedthose measurement methods by taking the long-ranged hydrodynamic interaction into account. The evaluatedforces have been compared with that obtained by the dual beam “optical trap” method, which is free from thehydrodynamic effect. The agreement between them is quantitatively fairly good.

*Hayato Shiba and Takeshi Kawasaki,
Spatiotemporal heterogeneity of local free volumes in highly supercooled liquid,
The Journal of Chemical Physics 139, 184502/1-8 (2013).

[Summary] We discussed the spatiotemporal behavior of local density and its relation to dynamical heterogeneity in a highly supercooled liquid by using molecular dynamics simulations of a binary mixture with different particle sizes in two dimensions. To trace voids heterogeneously existing with lower local densities, which move along with the structural relaxation, we employ the minimum local density for each particle in a time window whose width is set along with the structural relaxation time. Particles subject to free volumes correspond well to the configuration rearranging region of dynamical heterogeneity. While the correlation length for dynamical heterogeneity grows with temperature decrease, no growth in the correlation length of heterogeneity in the minimum local density distribution takes place. A comparison of these results with those of normal mode analysis reveals that superpositions of lower-frequency soft modes extending over the free volumes exhibit sp!atial correlation with the broken bonds. This observation suggests a possibility that long-ranged vibration modes facilitate the interactions between fragile regions represented by free volumes, to induce dynamical correlations at a large scale.

*Yuka Sakuma, Takashi Taniguchi, Toshihiro Kawakatsu, and Masayuki Imai,
Tubular membrane formation of binary giant unilamellar vesicles composed of cylinder and inverse-cone-shaped lipids,
Biophysical Journal 105, 2074-2081 (2013).

[Summary] We have succeeded in controlling tubular membrane formations in binary giant unilamellar vesicles (GUVs) using a simple temperature changing between the homogeneous one-phase region and the two-phase coexistence region. The binary GUV is composed of inverse-cone (bulky hydrocarbon chains and a small headgroup) and cylinder-shaped lipids. When the temperature was set in the two-phase coexistence region, the binary GUV had a spherical shape with solidlike domains. By increasing the temperature to the homogeneous one-phase region, the excess area created by the chain melting of the lipid produced tubes inside the GUV. The tubes had a radius on the micrometer scale and were stable in the one-phase region. When we again decreased the temperature to the two-phase coexisting region, the tubes regressed and the GUVs recovered their phaseseparated spherical shape. We infer that the tubular formation was based on the mechanical balance of the vesicle membrane (spontaneous tension) coupled with the asymmetric distribution of the inverse-cone-shaped lipids between the inner and outer leaflets of the vesicle (lipid sorting).

*Hiroaki Ito, Toru Yamanaka, Shou Kato, Tsutomu Hamada, Masahiro Takagi, *Masatoshi Ichikawa, *Kenichi Yoshikawa,
Dynamical formation of lipid bilayer vesicles fromlipid-coated droplets across a planar monolayer at an oil/water interface,
Soft Matter 9, 9539–9547 (2013).

[Summary] Recently, the transfer method has been shown to be useful for preparing cell-sized phospholipid bilayervesicles, within which desired substances at desired concentrations can be encapsulated, with a desiredasymmetric lipid composition. Here, we investigated the transfer process of water-in-oil (W/O) dropletscoated by phospholipid monolayers across an oil/water interface by both experimental observation andtheoretical modeling. Real-time experimental observation of the transfer revealed that the transferprocess is characterized by three kinetic regimes: a precontact process (approaching regime), an earlyfast process (entering regime), and a late slow process (relaxation regime). In addition, bigger dropletsrequire much more time to transfer than smaller droplets. We propose a theoretical model to interpretthis kinetic process. Our theoretical model reproduces the essential aspects of the transfer kinetics,including its size-dependence.

Tomo Kurimura, *Masatoshi Ichikawa, Masahiro Takinoue, *Kenichi Yoshikawa,
Back-and-forth micromotion of aqueous droplets in a dc electric field,
Physical Review E 88, 042918/1-5 (2013).

[Summary] Recently, it was reported that an aqueous droplet in an oil phase exhibited rhythmic back-and-forth motion under stationary dc voltage on the order of 100 V. Here, we demonstrate that the threshold voltage for inducing such oscillation is successfully decreased to the order of 10 V through downsizing of the experimental system. Notably, the threshold electric field tends to decrease with a nonlinear scaling relationship accompanied by the downsizing. We derive a simple theoretical model to interpret the system size dependence of the threshold voltage. This model equation suggests the unique effect of additional noise, which is qualitatively characterized as a coherent resonance by an actual experiment as a kind of coherent resonance. Our result would provide insight into the construction of micrometer-sized self-commutating motors and actuators in microfluidic and micromechanical devices.

*Yasutaka Iwashita and Yasuyuki Kimura,
Stable cluster phase of Janus particles in two dimensions,
Soft Matter 9, 10694-10698 (2013).

[Summary] A Janus colloidal particle with an attractive hemisphere has three valences, i.e. it can establish three bonds on the hemisphere in two dimensions. With experiments and simulations, we study how the stable cluster phase of the colloids depends on this attraction. With weak attraction, small micellar clusters form, and with strong attraction, these aggregate into linear chains; i.e., a micellar cluster behaves as a unit structure with two valences. Such hierarchical clustering plays a crucial role in the collective behavior of low-valence particles, in particular, for short-range interactions.

*David A. Head and Daisuke Mizuno,
Local mechanical response in semiflexible polymer networks subjected to an axisymmetric prestress,
Physical Review E 88, 022717/1-10 (2013).

[Summary] Analytical and numerical calculations are presented for the mechanical response of fiber networks in a stateof axisymmetric prestress, in the limit where geometric nonlinearities such as fiber rotation are negligible. Thisallows us to focus on the anisotropy deriving purely from the nonlinear force-extension curves of individualfibers. The number of independent elastic coefficients for isotropic, axisymmetric, and fully anisotropic networksare enumerated before deriving expressions for the response to a locally applied force that can be tested against, e.g., microrheology experiments. Localized forces can generate anisotropy away from the point of application, so numerical integration of nonlinear continuum equations is employed to determine the stress field, and induced mechanical anisotropy, at points located directly behind and in front of a force monopole. Results are presented for the wormlike chain model in normalized forms, allowing them to be easily mapped to a range of systems. Finally, the relevance of these findings to naturally occurring systems and directions for future investigation are discussed.

*Ryuichi Okamoto, Youhei Fujitani, and Shigeyuki Komura,
Drag coefficient of a rigid spherical particle in a near-critical binary fluid mixture,
Journal of the Physical Society of Japan 82, 084003/1-10 (2013).

[Summary] We calculate the drag coefficient of a rigid spherical particle in an incompressible binary fluid mixture. A weakpreferential attraction is assumed between the particle surface and one of the fluid components, and the difference in the viscosity between the two components is neglected. Using the Gaussian free-energy functional and solving the hydrodynamic equation explicitly, we can show that the preferential attraction makes the drag coefficient larger as the bulk correlation length becomes longer. The dependence of the deviation from the Stokes law on the correlation length, when it is short, turns out to be much steeper than the previous estimates.

*Yoshiyuki Kageyama, Naruho Tanigake, Yuta Kurokome, Sachiko Iwaki, *Sadamu Takeda, Kentaro Suzuki, and *Tadashi Sugawara,
Macroscopic motion of supramolecular assemblies actuated by photoisomerization of azobenzene derivatives,
Chemical Communications 49, 9386-9388 (2013).

[Summary] Submillimetre size self-assemblies composed of oleate and azobenzene derivatives show forceful motions such as screw-type coiling–recoiling motion by photoirradiation.

*Masakazu Iwasaka, Yuito Miyashita, Yuri Mizukawa, Kentaro Suzuki, Taro Toyota, and Tadashi Sugawara,
Biaxial Alignment Control of Guanine Crystals by Diamagnetic Orientation,
Applied Physics Express 6, 037002/1-4 (2013).

[Summary] The present study provides evidence that a kind of nucleic acid base crystal, guanine crystal, shows a distinct magnetic orientation. Under thecondition where the guanine crystal boards were lying on the glass surface due to gravity, the boards gradually oriented their length to the appliedhorizontal magnetic fields of 400 mT. On the other hand, the vertical magnetic fields parallel to Earth’s gravity caused their width to be orientedalong the applied magnetic fields. Moreover, combining both vertical and horizontal magnetic fields produced a rapid alignment of the length to thehorizontal magnetic fields.