Structural insights into the mechanical regulation of molecular recognition sites

Intriguing experimental and computational data are emerging to suggest that mechanical forces regulate the functional states of some proteins by stret ching them into nonequilibrium states. Using the, extracellular matrix prot ein fibronectin as an: example, we discuss molecular design principles that might control the exposure of a protein's recognition sites, and/or their relative distances, in a force-dependent manner. Fibronectin, regulates man y cellular functions by, binding directly to, integrins. Although integrins have a key role in the transduction of force across the cell, membrane by coupling the extracellular matrix to the cytoskeleton, the studies reviewed here suggest that fibronectin might be one of the molecules responsible fo r the initial transformation. of mechanical force into a biochemical. signa l.