Visualizing cellular force-sensing through the actin cytoskeleton

In addition to chemical cues, cells in the body must perceive physical forces at the molecular scale to orchestrate development and maintain homeostasis. Cells probe and respond to the physical properties of their local environments through the actin cytoskeleton, a network of protein polymers, motor proteins, and myriad associated partners. The Alushin lab studies how actin filaments serve as cellular tension sensors, engaging in force-sensitive binding interactions to transduce mechanical forces into biochemical signals. Different force regimes elicit specific conformational transitions in actin, suggesting the potential for a mechanical code that is interpreted by binding partners. These mechanical transitions are evoked through mechanisms distinct from standard biochemical regulation, providing a glimpse at how forces modulate protein structure to regulate function.