Abstract

The biological catch-bond is a fascinating and counterintuitive phenomenon, which was predicted theoretically 30 years ago. Recently, this predicted behavior has been observed in a number of protein receptor-ligand complexes. When an external force is applied to a catch-bond in an attempt to break it, either in vivo or in vitro, the bond resists breaking and becomes stronger instead. This is in contrast to ordinary slip-bonds which represent the vast majority of biological and chemical bonds and which dissociate faster when subjected to a force. This report focuses on the fundamental properties of catch-bonds and analyzes the simplest physical-chemical models to explain the experimental data. The simplicity of the theoretical treatment leads to analytic expressions for bond lifetime, concise universal representations of the experimental data, and explicit conditions required for catch-binding.Three different model of the biological catch-bond will be discussed, including the two pathway, deformation and allosteric models. Catch-binding is a consequence of a complex potential energy landscape in a biological receptor-ligand bond. Bond lifetime can increase with force, if this force prevents dissociation through a native pathway and instead drives the system over a higher energy barrier. The lifetime can also increase if the conformations of proteins in the complex are altered by the force in a way that strengthens receptor-ligand interaction. Such bond deformation can be associated with an allosteric effect, in which a conformational change at one end of the protein propagates to the binding site located at the other end. Both experiment and simulation indicate that catch-binding is accompanied by large-scale domain opening in the receptor protein. The models are used to describe catch-binding in P-selectin/PSGL-1, FimH/mannose, actin/myosin and integrin/fibronectin complexes.O. V. Prezhdo, Y. V. Pereverzev, “Theoretical aspects of the biological catch-bond”, Acc. Chem. Res., 42, 693 (2009).

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