Figure 1. Mechanosensing and mechanotransduction mechanisms in cells.

a, Cells have evolved to sense force either through protein-based mechanosensors or cytoskeletal and membrane-mediated molecular responses, in a process known as mechanosensing. Cells sense mechanical cues in multiple ways including; mechanosensitive ion channels, integrins in focal adhesions, cadherins in adheren junctions and nuclear membrane proteins in cytoskeletal interactions. b, Cells then translate these mechanical cues into biochemical signals that then elicit a biological response through a process termed mechanotransduction. In the case of focal adhesions, the initial activation and binding of integrins to the ECM can occur in the presence of low resisting forces (soft ECM), leading to the formation of a transient focal complex, where the integrin intracellular domain is weakly attached to F-actin. In the presence of high resisting forces (stiff ECM), the recruitment of adaptor proteins promotes integrin clustering, actin remodeling and myosin-mediated contraction to increase internal cellular tension. Force-bearing proteins such as talin undergo force-induced conformational changes, which promotes the local recruitment of other proteins to reinforce the linkage to actin, such as vinculin, to regulate local signaling to provide a positive feedback leading to further reinforcement and maturation of focal adhesions. Multiple mechanisms then contribute to regulate downstream signaling pathways mediating the biological responses to ECM mechanical cues. c, Examples of biological responses to ECM-derived mechanical cues occurring in different cell types. ECM cues influence cell-cell adhesions, regulates proliferation and apoptosis, directs cell migration and alters cell fate.