Effect of cell heterogeneity on isogenic populations with the synthetic genetic toggle switch network: bifurcation analysis of two-dimensional Cell Population Balance Models

摘要

The dynamics of gene regulatory networks are often modeled with theassumption of cellular homogeneity. However, this assumption contradicts theplethora of experimental results in a variety of systems, which designates thatcell populations are heterogeneous systems in the sense that properties such assize, shape, and DNA/RNA content are unevenly distributed amongst theirindividuals. In order to address the implications of heterogeneity, we utilizethe so-called cell population balance (CPB) models. Here, we solve numericallymultivariable CPB models to study the effect of heterogeneity on populationscarrying the toggle switch network, which features nonlinear behavior at thesingle-cell level. In order to answer whether this nonlinear behavior isinherited to the heterogeneous population level, we perform bifurcationanalysis on the steady-state solutions of the CPB model. We show thatbistability is present at the population level with the pertinent bistabilityregion shrinking when the impact of heterogeneity is enhanced.