  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.
