The effect of macromolecular crowding on the binding of ligands to a receptor near membranes is studied using Brownian dynamics simulations. The receptor is modeled as a reactive patch on a hard surface and the ligands and crowding agents are modeled as spheres that interact via a steep repulsive interaction potential. When a ligand collides with the patch, it reacts with probability prxn. The association rate constant (k&) can be decomposed into contributions from diffusion-limited (kD) and reaction-limited (kR) rates, i.e., 1/k∞ = 1/k D + 1/kR. The simulations show that kD is a nonmonotonic function of the volume fraction of crowding agents for receptors of small sizes. kR is always an increasing function of the volume fraction of crowding agents, and the association rate constant k ∞ determined from both contributions has a qualitatively different dependence on the macromolecular crowding for high and low values of the reaction probability prxn. The simulation results are used to predict the velocity of the membrane protrusion driven by actin filament elongation. Based on the simple model where the protrusive force on the membrane is generated by the intercalation of actin monomers between the membrane and actin filament ends, we predict that crowding increases the local concentration of actin monomers near the filament ends and hence accelerates the membrane protrusion.
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This article is based upon work supported by the National Science Foundation under grant No. CHE-0717569.