Catch-Bond Model Derived from Allostery Explains Force-Activated Bacterial Adhesion

Abstract

High shear enhances the adhesion of Escherichia coli bacteria binding to mannose coated surfaces via the adhesin FimH, raising the question as to whether FimH forms catch bonds that are stronger under tensile mechanical force. Here, we study the length of time that E. coli pause on mannosylated surfaces and report a double exponential decay in the duration of the pauses. This double exponential decay is unlike previous single molecule or whole cell data for other catch bonds, and indicates the existence of two distinct conformational states. We present a mathematical model, derived from the common notion of chemical allostery, which describes the lifetime of a catch bond in which mechanical force regulates the transitions between two conformational states that have different unbinding rates. The model explains these characteristics of the data: a double exponential decay, an increase in both the likelihood and lifetime of the high-binding state with shear stress, and a biphasic effect of force on detachment rates. The model parameters estimated from the data are consistent with the force-induced structural changes shown earlier in FimH. This strongly suggests that FimH forms allosteric catch bonds. The model advances our understanding of both catch bonds and the role of allostery in regulating protein activity.

Dynamic states of cells adhering in shear flow: From slipping to rolling

“…In principle, it would be easy to include more complicated rupture scenarios, like the catch-slip behavior recently reported for both P-and L-selectin [7,15]. There is good reason to believe that this molecular behavior is essential for the physiological function of these molecules and different theoretical models have been suggested to explain this behavior [63,64,65]. If combined with our modeling framework for adhesive dynamics, these models might be tested against experimental data from flow chamber experiments.…”

Resolving the molecular mechanism of cadherin catch bond formation

“…These include energy landscapes with one bound state and two unbinding pathways 43 ; an energy landscape with two bound states, one of which is preferentially stabilized by force 44,45 ; bond dissociation along a multidimensional landscape where the direction of the tensile force and the reaction coordinate are misaligned [46][47][48] ; a freeenergy landscape with dynamic disorder that thermally fluctuates with time 49,50 ; and allosteric deformation models where external force changes the structure of the receptor either directly at the ligand-binding site 51 or at a distal location that ultimately propagates the deformation to the binding pocket [52][53][54][55] . Our simulations suggest that X-dimers form catch bonds via a slidingrebinding mechanism where a pulling force flexes the ectodomain and slides opposing EC1 domains resulting in the formation of de novo, force-induced H-bonds.…”

Selectin catch–slip kinetics encode shear threshold adhesive behavior of rolling leukocytes

“…Although a variety of mechanisms and associated kinetic models have been postulated to explain the molecular basis for catchslip transitions (16,(19)(20)(21)(22), there remains little consensus regarding which description is most appropriate for selectins. This uncertainty is largely a consequence of the considerable number of theoretical parameters-4 or more-used to model lowdimensional force-lifetime data.…”