Molecular switches in the cell: fibronectin as a mechanical switch (Vogel, 2002) ? Fibronectin is an adhesion protein secreted by cells and assembled into fibrils to support adhesion and migration ? Composed of ‘modules’ of fibronectin repeats FnI, FnII, and FnIII connected by short linkers of varying flexibility ? One particular FnIII repeat, FnIII 10 , contains the RGD amino acid sequence ? FnIII modules have interesting force-responsive properties o undergo partial unfolding in response to physiological forces (Figure shows stretched FN repeats in fibrillar FN) ? integrins bind to and pull on FN fibers through the cytoskeleton o Several potential roles for this sensitivity: ? Expose buried recognition sites x So-called ‘cryptic’ sites in FnIII 1 , FnIII 7-8 , FnIII 10 , and FnIIII 14 ? Change relative distance between synergistic binding sites on 2 different modules x E.g. RGD synergy site between FnIII 9 and FnIII 10 ? Mechanical deformation and straightening of recognition sites on loops Structure of fibronectin (Vogel, 2002) Other examples of molecular switches in biology Adhesin adhesion protein in E. Coli: