Spatial Stochastic Dynamics Enable Robust Cell Polarization

Michael J. Lawson, Brian Drawert, Mustafa Khammash, Linda R. Petzold, Tau-Mu Yi

Abstract: Author Summary Cell polarity is the fundamental process of breaking symmetry to create asymmetric cellular structures. It is an open question how randomness (stochasticity) in the cell hinders or helps cell polarity. In this work, we focus on the ability of yeast cells to sense a spatial gradient of mating pheromone and respond by forming a projection in the direction of the mating partner. A key element is the polarisome, which is at the tip of the mating projection. We introduce the first model of polarisome formation in yeast. The model is well-supported by experimental data. We perform modeling to explore the role of noise in the formation of the polarisome. By running simulations with and without noise, we arrive at the surprising conclusion, that gradient-dependent polarization is enhanced by stochasticity. Both the tight localization (amplification) and the ability to respond to directional change of the input (tracking) are enhanced by stochastic dynamics, resulting in a more robust behavior. Mutants in which key polarisome proteins have been deleted exhibit broader, noisier polarisome than the wild type. The mutant phenotype is accurately captured by our stochastic simulations. These results demonstrate the importance of stochasticity in the study of cell polarity.