Mechanical force in nanoscale biology: from protein folding to enzyme kinetics

Wesley Wong
Rowlands Insitute, Harvard University

Many aspects of biological structure and function are governed by weak, non-covalent interactions between and within single molecules (e.g. DNA base-paring, protein folding, receptor-ligand binding, etc.) My group develops and applies novel single-molecule techniques to explore how mechanical force regulates the functioning of biological systems and modifies the kinetics of these interactions. For example, we have developed an advanced optical tweezers system, and have used it to investigate the role of force in the regulation of blood clotting. By determining the force-dependent kinetics of protein folding and enzyme activity, we have shown that hemostatic activity is largely regulated by physiological forces acting on a single-molecule mechanical switch, the A2 domain of von Willebrand factor (Zhang et al., Science, 2009). In my talk, I will describe this study, as well as the single-molecule methods that we have developed to enable these measurements. I will also describe some future research directions, including a new approach for performing massively parallel single-molecule force measurements that we call "single-molecule centrifugation".