Cell fate regulation by coupling mechanical cycles to biochemical signaling pathways.

Many aspects of cellular motility and mechanics are cyclic in nature such as the extension and retraction of lamellipodia or filopodia. Inherent to the cycles of extension and retraction that test the environment is the production of mechano-chemical signals that can alter long-term cell behavior, transcription patterns, and cell fate. We are just starting to define such cycles in several aspects of cell motility, including periodic contractions, integrin cycles of binding and release as well as the normal oscillations in motile activity. Cycles of local cell contraction and release are directly coupled to cycles of stressing and releasing extracellular contacts (matrix or cells) as well as cytoplasmic mechanotransducers. Stretching can alter external physical properties or sites exposed by matrix molecules as well as internal networks; thus, cell contractions can cause a secondary wave of mechano-regulated outside-in and internal cell signal changes. In some cases, the integration of both external and internal signals in space and time can stimulate a change in cell state from quiescence to growth or differentiation. In this review we will develop the basic concept of the mechano-chemical cycles and the ways in which they can be described and understood.