Integrins and Extracellular Matrix in Mechanotransduction

Integrins bind extracellular matrix fibrils and associate with intracellular actin filaments through a variety of cytoskeletal linker proteins to mechanically connect intracellular and extracellular structures. Each component of the linkage from the cytoskeleton through the integrin-mediated adhesions to the extracellular matrix therefore transmits forces that may derive from both intracellular, myosin-generated contractile forces and forces from outside the cell. These forces activate a wide range of signaling pathways and genetic programs to control cell survival, fate, and behavior. Additionally, cells sense the physical properties of their surrounding environment through forces exerted on integrin-mediated adhesions. This article first summarizes current knowledge about regulation of cell function bymechan-ical forces acting through integrin-mediated adhesions and then discusses models for mechanotransduction and sensing of environmental forces. The fact that multicellular organisms canresist the wide range of physical forces en-countered in nature requires appropriate me-chanical connectivity within each tissue. For example, skin and other epithelial tissues hav