Fig. 5.

Schematic diagram of structures potentially involved in mechanotransduction during stiffness sensing. In the resting cell, the ECM is linked to the cell interior by linkages among ECM proteins (1), transmembrane adhesion receptors (2), one or more proteins (3) that bind transmembrane proteins to cytoskeletal filaments (4) to which forces can be applied by motors (5). The resulting tension can deform any of these elements in series or can be transmitted through the membrane (6) to affect enzymes and other proteins (7) that are physically linked to it. The motor-generated force and the transmitted tension can potentially unfold extracellular proteins to expose a new receptor activating site (*), activate a transmembrane receptor (*), unfold an intracellular protein active site (*), recruit proteins to regions of increased membrane curvature, or transmit force through the cytoskeleton to an interior target such as the nucleus. The tension can also change the stability of motor-filament or clutch protein-filament binding through activation of catch bonds or slip-bonds.