Physical limits to mechanical and chemical sensing of fluid flow direction

Cells sense and respond to many types of directional cue. Whereas the physical limits to the precision of chemosensing are well known, similar limits for mechanosensing are still poorly understood. Directional mechanosensing mechanisms include the use of mechanosensitive ion channels to report membrane tension differentials, and the use of focal adhesions to the surrounding extracellular matrix to report force differentials. We develop a global framework that describes the sensory precision of multiple types of directional sensing from a statistical mechanics perspective. Specializing to simple models of mechanosensing in response to fluid flow, we calculate their physical limits and compare them with that of chemosensing, which in some contexts competes. We then apply our results to experiments on migratory cancer cell lines in the presence of flow to predict how cells negotiate these potentially competing migratory cues during metastatic invasion.