Fig. 4: Multiscale mechanoadaptation as a rationale for design of engineering tissue templates, materials or devices for regenerative medicine and for physical therapy protocols in the context of cytoskeletal remodeling.

Transfer of forces  experienced by an organism to its constituent organs, tissues, and cells (left, top to bottom) drives the multiscale structure–function adaptation of the cytoskeleton, cells, tissues and organs, to the dynamic mechanical environment of the organism, which is essential to healing (right, bottom to top). At the molecular level, focal adhesion complexes mediate outside-in signaling and mechanically link tissue rigidity to cytoskeleton dynamics, regulating cytoskeletal interactions with adapter proteins, and force transduction to the nucleus. The mechanical signals, transduced as actin and microtubule dynamics, determine cell shape and force generation, resulting in tension equilibrium at tissue and other length scales (adapted with permission from ref. ²).