Potential and flux landscapes quantify the stability and robustness of budding yeast cell cycle network

Abstract

Studying the cell cycle process is crucial for understanding cell growth, proliferation, development, and death. We uncovered some key factors in determining the global robustness and function of the budding yeast cell cycle by exploring the underlying landscape and flux of this nonequilibrium network. The dynamics of the system is determined by both the landscape which attracts the system down to the oscillation orbit and the curl flux which drives the periodic motion on the ring. This global structure of landscape is crucial for the coherent cell cycle dynamics and function. The topography of the underlying landscape, specifically the barrier height separating basins of attractions, characterizes the capability of changing from one part of the system to another. This quantifies the stability and robustness of the system. We studied how barrier height is influenced by environmental fluctuations and perturbations on specific wirings of the cell cycle network. When the fluctuations increase, the barrier height decreases and the period and amplitude of cell cycle oscillation is more dispersed and less coherent. The corresponding dissipation of the system quantitatively measured by the entropy production rate increases. This implies that the system is less stable under fluctuations. We identified some key structural elements for wirings of the cell cycle network responsible for the change of the barrier height and therefore the global stability of the system through the sensitivity analysis. The results are in agreement with recent experiments and also provide new predictions.