The Effect of Membrane Receptor Clustering on Spatio- temporal Cell Signalling Dynamics

International audienceMembrane receptors allow the cell to respond to changes in the composition of its external medium. The ligand-receptor interaction is the core of the signalling process and may be greatly influenced by the spatial configuration of receptors. As growing pieces of evidence suggest that receptors are not homogeneously spread on the cell surface, but tend to form clusters, we propose to investigate the implication of receptor clustering on ligand binding kinetics using a computational individual-based model. The model simulates the activation of receptors distributed in clusters or uniformly spread. The tracking of binding events allows the analysis of the effect of receptor clustering through the autocorrelation of the receptor activation signal and the empirical time distributions of binding events, which are still unreachable with in vitro or in vivo experiments. Results show that the apparent affinity of clustered receptors is decreased. Additionally, receptor occupation becomes spatially and temporally correlated, as clustering creates platforms of coherently activated receptors. Changes in the spatial characteristics of a signalling system at the microscopic scale globally affect its function in time and space