Keynote Lecture of the Molecular Biophysics Training Grant Symposium
Molecular Biophysics and Applications of an Allosteric Catch Bond
Catch bonds are receptor-ligand interactions that are strengthened by tensile mechanical force. The bacterial adhesin FimH provides a model system for understanding the molecular biophysics of catch bonds and the role of catch bonds in cell biology. The Thomas lab uses an interdisciplinary approach that includes genetic engineering, single molecule force spectroscopy, atomistic structural analysis and simulations and mathematical modeling. This work has enabled us to understand how catch bond behavior is caused by force-regulated allosteric conformational changes. The Thomas lab also studies how catch bonds contribute to bacterial adhesion in flow. Specifically we have determined how catch bonds, together with the fimbrial organelles on which they are expressed, allow bacteria to have mobility when conditions are safe, but to lock on when wrenched by high flow. This function is reminiscent of a nanoscale locking seatbelt, and has inspired several adhesive applications for FimH catch bonds. This talk will conclude with a discussion of how the lessons from FimH can provide insight into the biophysics of other molecules and cells.