Membrane Ruffling is a Mechanosensor of Extracellular Fluid Viscosity.

Cell behaviour is affected by the physical forces and mechanical properties of the cells and of their microenvironment. The viscosity of extracellular fluid - a component of the cellular microenvironment - can vary by orders of magnitude, but its effect on cell behaviour remains largely unexplored. Using bio-compatible polymers to increase the viscosity of the culture medium, we characterize how viscosity affects cell behaviour. We find that multiple types of adherent cells respond in an unexpected but similar manner to elevated viscosity. In a highly viscous medium, cells double their spread area, exhibit increased focal adhesion formation and turnover, generate significantly greater traction forces, and migrate nearly two times faster. We observe that when cells are immersed in regular medium, these viscosity-dependent responses require an actively ruffling lamellipodium - a dynamic membrane structure at the front of the cell. We present evidence that cells utilize membrane ruffling to sense changes in extracellular fluid viscosity and to trigger adaptive responses.