Hierarchical phase transitions as mechanical checkpoints of intracellular organization

TL;DR

This study uncovers how mechanical cues induce hierarchical phase transitions in intracellular actin structures, acting as checkpoints that regulate cell organization during spreading.

Contribution

The paper introduces a thermodynamic framework explaining actin reorganization as a hierarchy of phase transitions driven by mechanical stiffness.

Findings

Actin structures undergo stiffness-dependent transitions from disordered to bundled states.

Senescent fibroblasts exhibit similar actin reorganizations despite reduced biochemical activity.

A statistical-mechanical model explains these transitions as energy-entropy driven thresholds.

Abstract

Living cells inherently reorganize their intracellular structures in response to mechanical cues from their environment. Among these responses, the formation of actin-based stress fibers exhibits a series of structural transitions depending on substrate stiffness: from disordered states on soft substrates, to partial alignment, and eventually to bundled formations as stiffness increases. While these transformations have been well documented in many cell types, the physical principles underlying their emergence remain elusive. Here, we observe identical stiffness-dependent actin reorganizations in senescent fibroblasts despite their diminished biochemical and metabolic activities, suggesting that physical constraints play a dominant role in the phenomenon. We then develop a statistical-mechanical framework to demonstrate that these changes arise through a hierarchy of threshold-dependent phase transitions dictated by energy-entropy competition. This formulation provides a thermodynamic basis for understanding how distinct cytoskeletal orders become favored under different mechanical regimes. We propose that these transitions serve as mechanical checkpoints that coordinate intracellular organization during G1-phase spreading. These findings reveal how mechanical cues guide distinct intracellular orders through a physically constrained hierarchy of transitions.