Impact of receptor clustering on ligand binding

We implemented a model of receptor binding using a Monte-Carlo algorithm to simulate ligand diffusion and binding. In some simple cases, analytic solutions for binding equilibrium of ligand on clusters of receptors are provided, and supported by simulation results. Our simulations show that the so-called "apparent" affinity of the ligand for the receptor decreases with clustering although the microscopic affinity remains constant.Changing membrane receptors clustering could be a simple mechanism that allows cells to change and adapt its affinity/sensitivity toward a given stimulus.The binding kinetics between cell surface receptors and extracellular biomolecules are critical to all intracellular and intercellular activity. Modelling and predicting of receptor-mediated cell functions are facilitated by measurement of the binding properties on whole cells. Therefore, these measurements, however elaborate, have been based on the ground of chemical enzyme/substrate formalism [1-4]. Such formulations were derived from the law of mass-action that evaluates local reaction rates from averaged chemical species densities over the medium volume. Mass-action laws are mean-field approximations because they evaluate local reaction rates on the basis of average values of the reactant density over a large spatial domain. In addition, it amounts to assume that ligand/receptor interactions are independent [5,6].These assumptions may fail in real biological systems, in particular considering membrane receptors which are restricted to only 2 of the 3 spatial dimensions [7,8]. The effect of binding kinetics for membrane-restricted receptors (on spherical cells) has already been investigated by Berg and Purcell [9]. This study focused on the spatial restriction of receptors to a 2D support while interacting with bulk ligand diffusing in a 3 D medium, and resulted in an expression for reaction rate coefficients as non-linear functions of cell surface receptor density. This pioneer study h