Dr. Jizhong Lou
Georgia Institute of Technology
Atlanta, GA

Monday, September 17, 2007
3:00 pm (CT)
3269 Beckman Institute

Abstract

Force can shorten the lifetimes of macromolecular complexes (e.g., receptor/ligand bonds) by accelerating their dissociation. Perhaps paradoxical at first glance, bond lifetimes can also be prolonged by force. This counterintuitive behavior was named catch bonds, which is in contrast to the ordinary slip bonds that describe the intuitive behavior of lifetimes being shortened by force. Catch bonds have been observed in selectin/ligand interactions and other systems. We study changes in structure and atomic-level interactions during forced unbinding of selectins from their ligands with molecular dynamics simulations. A mechanistic sliding-rebinding model is developed based on the observations. In the model, "catch" results from forced opening of an inter-domain hinge which promotes sliding and rebinding. The model is further supported by site-direct mutagenesis in L-selectin.