Membrane ruffling is a mechanosensor of extracellular fluid viscosity

Throughout the body, cells are immersed in extracellular fluids (ECFs) that are typically orders of magnitude more viscous than water or culture medium. Changes in the viscosity of biological fluids are associated with physiological processes and diseases ranging from wound healing to cystic fibrosis to cancer. However, unlike the material properties of the extracellular matrix, the role of ECF viscosity has not been thoroughly studied. Here we characterize the cellular response to viscosity, which causes dramatic increases in cell area, traction force generation, and cell speed, and present a mechanism by which membrane ruffling acts as a mechanosensor of ECF viscosity.