Extracellular matrix–dependent mechanosensing and mechanotransduction

The extracellular matrix (ECM) is a complex network of macromolecular proteins and proteoglycans that have a vital structural and functional role in cell and tissue organization. Cells attached to or embedded in the ECM respond to biochemical and mechanical cues from the ECM to regulate cellular function, including migration. Cells respond not just to forces but also to associated deformations exerted on the ECM. The composition and cross-linking of matrix proteins (collagen, elastin, fibronectin, and matricellular proteins) regulates ECM topology and stiffness. The cellular response to these diverse mechanical cues is initiated by one or more mechanosensors that trigger distinct downstream signaling pathways (mechanotransduction). We evaluate the role plasma membrane (caveolae, ion channels, and glycocalyx), integrins, cytoskeleton, and nucleus have in cellular mechanosensing and transduction to drive matrix stiffness–dependent cell migration.