More than a feeling: discovering, understanding, and influencing mechanosensing pathways

The ability of cells to extract biophysical information from their extracellular environment and convert it to biochemical signals is known as mechanotransduction. Here we detail three passive, ‘inside-out’ mechanotransduction mechanisms with an emphasis on the mechanosensing pathways involved in creating these signal: Rho/ROCK, stretch-activated channels, and ‘Molecular Strain Gauges.’ We also examine how molecular tools have been used to perturb these pathways to better understand their interconnectivity. However, perturbing pathways may have unintended confounding effects, which must also be addressed. By discovering and understanding mechanosensitive pathways, the ability to influence them for clinical applications increases.

► ‘Inside-out’ mechanotransduction is examined with an emphasis on mechanosensing pathways.
► The three paradigms of ‘inside-out’ mechanotransduction pathways are Rho/ROCK, Stretch-Activated Channels, and ‘Molecular Strain Gauges’.
► The design of systems to perturb these pathways allows for a better understanding of their interconnectivity.
► Perturbing pathways may have unintended confounding effects.