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

TL;DR

This paper develops a self-consistent stochastic theory for reversible ligand binding to spherical cells, revealing time-dependent modifications to association/dissociation rates and challenging traditional assumptions like the Berg-Purcell scaling.

Contribution

The authors introduce a novel self-consistent stochastic framework that captures the full kinetics of ligand-receptor interactions, including rebinding effects and time-dependent rate modifications.

Findings

Effective on-rate varies non-monotonically over time.

Dissociation rate is significantly affected by rebinding events.

At equilibrium, ligand concentration is uniform and matches the spatial mean.

Abstract

In this article, 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 solution is the same and equals its spatial mean, thus ensuring that there is no depletion in the vicinity of the cell. Implications of our results for binding experiments and numerical simulations of ligand-receptor systems are also discussed.