Self-consistent theory of reversible ligand binding to a spherical cell

Physical Biology
Shivam GhoshKimberly Forsten-Williams

Abstract

Ligand binding to receptors is the initial event in many signaling processes, and a quantitative understanding of this interaction is important for modeling cell behavior. In this paper, we study the kinetics of reversible ligand binding to receptors on a spherical cell surface using a self-consistent stochastic theory. Binding, dissociation, diffusion and rebinding of ligands are incorporated into the theory in a systematic manner. We derive explicitly the time evolution of the ligand-bound receptor fraction p(t) in various regimes. Contrary to the commonly accepted view, we find that the well-known Berg-Purcell scaling for the association rate is modified as a function of time. Specifically, the effective on-rate changes non-monotonically as a function of time and equals the intrinsic rate at very early as well as late times, while being approximately equal to the Berg-Purcell value at intermediate times. The effective dissociation rate, as it appears in the binding curve or measured in a dissociation experiment, is strongly modified by rebinding events and assumes the Berg-Purcell value except at very late times, where the decay is algebraic and not exponential. In equilibrium, the ligand concentration everywhere in the solu...Continue Reading

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Citations

Jul 19, 2013·BioMed Research International·Alex Skvortsov, Peter Gray
Sep 8, 2011·Theoretical Biology & Medical Modelling·Vladas SkakauskasAlex Skvortsov
Apr 2, 2011·BMC Systems Biology·Bertrand R Caré, Hédi A Soula
Feb 16, 2013·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Bertrand R Caré, Hédi A Soula

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