Approximating the effects of diffusion on reversible reactions at the cell surface: ligand-receptor kinetics.

Abstract

We consider the problem of determining the time dependence of the bound ligand concentration for the reversible binding of a diffusing monovalent ligand to receptors uniformly distributed over the surface of a spherical cell. We start by formulating a boundary value problem that captures the essential physics of this situation. We then introduce a systematic approximation scheme based on the method of weighted residuals. By this means we convert the initial boundary value problem into a simpler problem that requires solving only a small number of ordinary differential equations. We show how, at the lowest order of approximation, the method can be used to obtain modified chemical rate equations where, in place of fundamental rate constants, effective rate coefficients appear. These rate coefficients are functions of the ligand diffusion coefficient, the cell radius, the receptor density and other variables. We compare exact and approximate solutions and discuss under what conditions the approximate equations can be used. We also apply the method of weighted residuals to obtain approximate descriptions of the binding kinetics when (1) there are two different cell surface receptor populations that bind the ligand and (2) the cell secretes a ligand that can bind back to receptors on the cell (autocrine binding).