Intracellular order formation through stepwise phase transitions

Abstract: Living cells inherently exhibit the ability to spontaneously reorganize their structures in response to changes in both their internal and external environments. Among these responses, the organization of stress fibers composed of actin molecules changes in direct accordance with the mechanical stiffness of their environments. On soft substrates, SFs are rarely formed, but as stiffness increases, they emerge with random orientation, progressively align, and eventually form thicker bundles as stiffness surpasses successive thresholds. These transformations share similarities with phase transitions studied in condensed matter physics, yet despite extensive research on cellular dynamics, the introduction of the statistical mechanics perspective to the environmental dependence of intracellular structures remains underexplored. With this physical framework, we identify key relationships governing these intracellular transitions, highlighting the delicate balance between energy and entropy. Our analysis provides a unified understanding of the stepwise phase transitions of actin structures, offering new insights into related biological mechanisms. Notably, our study suggests the existence of mechanical checkpoints in the G1 phase of the cell cycle, which sequentially regulate the formation of intracellular structures to ensure proper cell cycle progression.