We’ve just published a paper in Science Magazine in collaboration with Timothy A. Springer’s group. Using techniques in single-molecule manipulation, we have studied a fundamental feedback mechanism that the body uses to regulate the clotting of blood. The A2 domain of von Willebrand factor is the key to this largely mechanical molecular feedback loop. Using optical tweezers, we have characterized the unfolding and refolding kinetics of the A2 domain, and have shown that force acts as an “cofactor”, enabling the cleavage of A2 by the ADAMTS13 enzyme. Furthermore, the hydrodynamic tensile forces encountered by VWF in the circulation are sufficient to enable cleavage, which in turn down regulates the body’s hemostatic potential.