Clusters of Proteins in Biomembranes: Insights into the Roles of Interaction Potential Shapes and of Protein Diversity

It has recently been proposed that proteins embedded in lipidic biomembranes can spontaneously self-organize into stable small clusters, or membrane nanodomains, due to the competition between short-range attractive and longer-range repulsive forces between proteins, specific to these systems. In this paper, we carry on our investigation, by Monte Carlo simulations, of different aspects of cluster phases of proteins in biomembranes. First, we compare different long-range potentials (including notably three-body terms) to demonstrate that the existence of cluster phases should be quite generic.. Furthermore, a real membrane contains hundreds of different protein species that are far from being randomly distributed in these nanodomains. We take this protein diversity into account by modulating protein protein interaction potentials both at short and longer range. We confirm theoretical predictions in terms of biological cluster specialization by deciphering how clusters recruit only a few protein species. In this respect, we highlight that cluster phases can turn out to be an advantage at the biological level, for example by enhancing the cell response to external stimuli.