Crowding Effects on Association Reactions at Membranes

Abstract

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. The association rate constant can be decomposed into contributions from diffusion-limited and reaction-limited rates. The simulations show that the diffusion-limited rate is a non-monotonic function of the volume fraction of crowding agents for receptors of small sizes. This is because crowding decreases the rate of diffusion to the surface but inhibits the escape of the ligand from the vicinity of the surface. The association rate constant has a qualitatively different dependence on the macromolecular crowding, for different values of the reaction probability. 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.