Topology of molecular deformations induces triphasic catch bonding in selectin-ligand bonds
Among the long-standing efforts to elucidate the physical mechanisms of protein-ligand catch bonding, particular attention has been directed at the family of selectin proteins. Selectins exhibit slip, catch-slip, and slip-catch-slip bonding, with minor structural modifications causing major changes in selectins response to force. How can a single structural mechanism allow interconversion between these various behaviors? We present a unifying theory of selectin-ligand catch bonding, using a structurally-motivated free energy landscape to show how the topology of force-induced deformations of the molecular system produce the full range of observed behaviors. Our novel approach can be applied broadly to other protein-ligand catch bonds, and our results have implications for such future models. In particular, our model exhibits a severe breakdown of Bells theory--a paradigmatic theory that is widely invoked in theories of catch bonding. This raises questions about the suitability of Bells theory in modeling other catch bonds.