Cellular Biology in Terms of Stochastic Nonlinear Biochemical Dynamics: Emergent Properties, Isogenetic Variations and Chemical System Inheritability

Abstract

Based on a stochastic, nonlinear, open biochemical reaction system perspective, we present an analytical theory for cellular biochemical processes. The chemical master equation (CME) approach provides a unifying mathematical framework for cellular modeling. We apply this theory to both self-regulating gene networks and phosphorylation-dephosphorylation signaling modules with feedbacks. Two types of bistability are illustrated in mesoscopic biochemical systems: one that has a macroscopic, deterministic counterpart and another that does not. In certain cases, the latter stochastic bistability is shown to be a “ghost” of the extinction phenomenon. We argue the thermal fluctuations inherent in molecular processes do not disappear in mesoscopic cell-sized nonlinear systems; rather they manifest themselves as isogenetic variations on a different time scale. Isogenetic biochemical variations in terms of the stochastic attractors can have extremely long lifetime. Transitions among discrete stochastic attractors spend most of the time in “waiting”, exhibit punctuated equilibria. It can be naturally passed to “daughter cells” via a simple growth and division process. The CME system follows a set of nonequilibrium thermodynamic laws that include non-increasing free energy F(t) with external energy drive Q hk ≥0, and total entropy production rate e p =−dF/dt+Q hk ≥0. In the thermodynamic limit, with a system’s size being infinitely large, the nonlinear bistability in the CME exhibits many of the characteristics of macroscopic equilibrium phase transition.