An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns

Rho GTPase-based signaling networks control cellular dynamics by coordinating protrusions and retractions in space and time. Here, we reveal a signaling network that generates pulses and propagating waves of cell contractions. These dynamic patterns emerge via self organization from an activator-inhibitor network, in which the small GTPase Rho amplifies its activity by recruiting its activator, GEF-H1. Rho also inhibits itself by local recruitment of acto myosin and the associated RhoGAP Myo9b. This network structure enables spontaneous, self limiting patterns of subcellular contractility that can explore mechanical cues in the extracellular environment. Indeed, acto-myosin pulse frequency in cells is altered by matrix elasticity, showing that coupling of contractility pulses to environmental deformations modulates network dynamics. Thus, our study reveals a mechanism that integrates intracellular biochemical and extracellular mechanical signals into subcellular activity patterns to control cellular contractility dynamics.