Mechanoadaptive focal adhesion-actomyosin coupling organizes diverse modes across ECM stiffness

Abstract

Focal adhesions mechanically couple the actomyosin cytoskeleton to the extracellular matrix (ECM), contributing to mechanosensing and mechanical homeostasis. They span diverse states in response to the mechanical environment, from nascent adhesions and focal complexes to mature and supermature adhesions, undergoing dynamic remodeling. However, how ECM-dependent force generation and internal mechanoadaptation jointly shape the emergence and stability of these states remains unclear. Here, we develop a four-variable dynamical model comprising adhesion state, transmitted force, reinforcement activity, and an adaptive mechanical stress target. As ECM stiffness varies, the model generates distinct modes while regulating mechanical stress toward this target. The force-response timescale further modifies the stability structure, giving rise to a stable oscillatory mode. Within multistable regimes, adhesion-mode selection depends not only on current ECM stiffness but also on its history. These results show that diverse adhesion modes can emerge from a common mechanoadaptive system, with ECM stiffness history influencing mode selection.