The Sliding–Rebinding Mechanism for Catch Bonds

Abstract

Catch bonds, in which bond lifetime increases with force, have been demonstrated experimentally. This discovery has sparked great interest in physically modeling such a counterintuitive phenomenon. Here, we summarize the results of our recent study on selectin crystal structures, molecular dynamics simulations, Monte Carlo modeling, site-directed mutagenesis, single-molecule force and kinetics experiments, and flow chamber adhesion studies that support a sliding–rebinding mechanism for catch bonds. In the model, “catch” results from the forced opening of an interdomain hinge that tilts the binding interface to allow two sides of the contact to slide against each other. Sliding promotes formation of new interactions and even rebinding to the original state, thereby slowing dissociation and prolonging bond lifetimes. This model provides a possible explanation for how external forces allosterically modulate atomic-level noncovalent interactions at the binding interface to regulate dissociation pathways.