PHYS 68 |
| While the adhesive strength of most receptor-ligand interactions is drastically reduced if strained, some receptor-ligand complexes exist that strengthen under force which is the hallmark of catch bonds. The discovery that certain bacteria can tightly bind to surfaces under flow conditions through the formation of catch bonds contradicted the longterm believe that flow would wash off bacteria from surfaces rather than promoting their tight binding. The implications for the development of strategies to combat bacterial infections are profound. Although the existence of catch bonds was theoretically predicted, the first experimental demonstrations of their existence were given only recently, i.e. for the bacterial adhesin FimH that is located at the tip of type I fimbriae of E. coli and for p-selectin. In a major collaborative effort, we study the structural origin by which the FimH-mannose bond can be switched to a high binding state. Mutational studies are thereby combined with steered molecular dynamic simulations to decipher at high resolution how force might affect protein conformation. Force-activation of FimH furthermore leads to a complex ?stick-and-roll? bacterial adhesion behavior in which E. coli preferentially rolls over mannosylated surfaces at low shear but increasingly stick firmly as the shear is increased. As the FimH adhesin is exposed at the tip of fimbriae, we finally asked whether the mechanical properties of fimbriae through which force is transmitted to the receptor-ligand pairs are tuned to optimize bacterial adhesion. |
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Frontiers in Single-Molecule Biophysical Chemistry and Imaging
1:20 PM-5:00 PM, Sunday, 10 September 2006 Grand Hyatt San Francisco -- Plaza Ballroom East, Oral
Division of Physical Chemistry |