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.