Global quantitative understanding of nonequilibrium cell fate decision making in response to pheromone

Cell cycle arrest and polarized cell growth are commonly used to qualitatively characterize the fate of yeast in response to pheromone. However, the quantitative decision-making process underlying the time-dependent changes in cell fate remains unclear. Here, by observing the multi-dimensional responses at the single-cell level experimentally, we find that yeast cells have various fates. Multiple states are revealed, along with the kinetic switching rates and pathways among them, giving rise to a quantitative landscape of mating response. We developed a theoretical framework using a nonequilibrium landscape and flux theory to account for the cell morphology observed experimentally and performed a stochastic simulation of biochemical reactions to explain the signal transduction and cell growth. Our experimental results established the first global quantitative demonstration of the real-time synchronization of intracellular signaling with their physiological growth and morphological functions which reveals the underlying physical mechanism. This study provides an emerging mechanistic approach for understanding the nonequilibrium global pheromone-regulated cell fate decision-making in growth and morphology.