Balancing reaction-diffusion network for cell polarization pattern with stability and asymmetry

Abstract

Cell polarization is a critical process that separates molecules into two distinct regions in prokaryotic and eukaryotic cells, guiding biological processes such as cell division and cell differentiation. Although several underlying antagonistic reaction-diffusion networks capable of setting up cell polarization have been identified experimentally and theoretically, our understanding of how to manipulate pattern stability and asymmetry remains incomplete, especially when only a subset of network components are known. Here we present numerical results to show that the polarized pattern of an antagonistic 2-node network collapses into a homogeneous state when subjected to single-sided self-regulation, single-sided additional regulation, or unequal system parameters. However, polarity can be restored through a combination of two modifications that have opposing effects. Additionally, spatially inhomogeneous parameters favoring respective domains stabilize their interface at designated locations. To connect our findings to cell polarity studies of the nematode Caenorhabditis elegans zygote, we reconstituted a 5-node network where a 4-node circuit with full mutual inhibitions between anterior and posterior is modified by a mutual activation in the anterior and an additional mutual inhibition between the anterior and the posterior. Once again, a generic set of kinetic parameters moves the interface towards either the anterior or posterior end, yet a polarized pattern can be stabilized through spatial tuning of one or more parameters coupled to intracellular or extracellular cues. A user-friendly software, PolarSim, is introduced to facilitate the exploration of networks with alternative node numbers, parameter values, and regulatory pathways.