[hal-01070253] Impact of receptor clustering on ligand binding

Background Cellular response to changes in the concentration of different chemical species in the extracellular medium is induced by ligand binding to dedicated transmembrane receptors Receptor density distribution and clustering may be key spatial features that influence effective and proper physical and biochemical cellular responses to many regulatory signals Classical equations describing this kind of binding kinetics assume the distributions of interacting species to be homogeneous neglecting by doing so the impact of clustering As there is experimental evidence that receptors tend to group in clusters inside membrane domains we investigated the effects of receptor clustering on cellular receptor ligand binding Results 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 Conclusions Changing membrane receptors clustering could be a simple mechanism that allows cells to change and adapt its affinity/sensitivity toward a given stimulus



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