EGFR autocrine signaling in a compliant interstitial space: Mechanotransduction from the outside in

Cells transduce mechanical forces into biochemical signals; traditionally these processes are thought to occur through direct effects on the cell membrane, the cytoskeleton, or specific transmembrane proteins. In multicellular tissues mechanical forces alter intercellular spacing through redistribution of interstitial fluid. Recent morphological and biochemical observations, bolstered by analytical modeling, support a new paradigm for mechanotransduction arising from constitutive growth factor shedding into a dynamically regulated interstitial volume.