Whole-cell modeling framework in which biochemical dynamics impact aspects of cellular geometry

A mathematical framework for modeling biological cells from a physicochemical perspective is described. Cells modeled within this framework consist of at least two regions, including a cytosolic volume encapsulated by a membrane surface. The cytosol is viewed as a well-stirred chemical reactor capable of changing volume while the membrane is assumed to be an oriented 2-D surface capable of changing surface area. Two physical properties of the cell, namely volume and surface area, are determined by (and determine) the reaction dynamics generated from a set of chemical reactions designed to be occurring in the cell. This framework allows the modeling of complex cellular behaviors, including self-replication. This capability is illustrated by constructing two self-replicating prototypical whole-cell models. One protocell was designed to be of minimal complexity; the other to incorporate a previously reported well-known mechanism of the eukaryotic cell cycle. In both cases, self-replicative behavior was achieved by seeking stable physically possible oscillations in concentrations and surface-to-volume ratio, and by synchronizing the period of such oscillations to the doubling of cytosolic volume and membrane surface area. Rather than being enforced externally or artificially, growth and division occur naturally as a consequence of the assumed chemical mechanism operating within the framework.