Quantifying nonequilibrium dynamics and thermodynamics of cell fate decision making in yeast under pheromone induction.

Cellular responses to pheromone in yeast can range from gene expression to morphological and physiological changes. While signaling pathways are well studied, the cell fate decision-making during cellular polar growth is still unclear. Quantifying these cellular behaviors and revealing the underlying physical mechanism remain a significant challenge. Here, we employed a hidden Markov chain model to quantify the dynamics of cellular morphological systems based on our experimentally observed time series. The resulting statistics generated a stability landscape for state attractors. By quantifying rotational fluxes as the non-equilibrium driving force that tends to disrupt the current attractor state, the dynamical origin of non-equilibrium phase transition from four cell morphological fates to a single dominant fate was identified. We revealed that higher chemical voltage differences induced by a high dose of pheromone resulted in higher chemical currents, which will trigger a greater net input and, thus, more degrees of the detailed balance breaking. By quantifying the thermodynamic cost of maintaining morphological state stability, we demonstrated that the flux-related entropy production rate provides a thermodynamic origin for the phase transition in non-equilibrium morphologies. Furthermore, we confirmed that the time irreversibility in time series provides a practical way to predict the non-equilibrium phase transition.