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New approaches in force spectroscopy: from enzyme kinetics to single-molecule centrifugation


Many aspects of biological function and structure are governed by weak non-covalent bonds between and within single molecules. My research group develops and applies new methods in single-molecule manipulation to understand the dynamics of these interactions. This talk will consist of two parts. First, I will discuss how we have used optical tweezers to investigate von Willebrand Factor, a critical blood clotting protein. In particular, we have shown that hemostatic activity is largely regulated by physicological forces acting on a single-molecule mechanical switch [1]. In the second part of the talk, I will introduce a new technique that we have developed for performing massively parallel single-molecule force measurements: single-molecule centrifugation [2]. As a demonstration of this approach, we have characterized the force-dependent unbinding kinetics of an antibody-antigen pair by performing thousands of simultaneous single-molecule measurements with a new instrument that we call the Centrifuge Force Microscope.

[1] X. Zhang, K. Halvorsen, C.-Z. Zhang, W.P. Wong, and T.A. Springer, “Mechanoenzymatic cleavage of the ultralarge vascular protein, von Willebrand Factor,” Science 324 (5932), 1330-1334 (2009).

[2] K. Halvorsen, W.P. Wong, “Massively parallel single-molecule manipulation using centrifugal force,” Biophysical Journal 98 (11), L53-L55 (2010).