(174b) Hydrophobic Mismatch Can Induce Specific and Selective Membrane Protein Interactions

The composition of the lipid membrane and the hydrophobic matching between the lipid bilayer hydrophobic thickness and the hydrophobic length of the transmembrane proteins are important physical properties that regulate the mechanism of lipid-protein interactions in biomembranes. These could play a far more important role in the decision of the protein topology after insertion in the membrane, in the regulation of the protein activity, in protein aggregation of misfolded proteins and in signal transduction, than is presently supposed. However, experimentally it is difficult to isolate and hence to study solely the interactions due to hydrophobic forces. We use free energy calculations and MD simulations of a coarse grain model of a lipid bilayer with embedded proteins to show that hydrophobic forces induce specific and selective protein-protein interactions. The nature of the protein interactions, i.e., repulsion, temporary oligomerization and protein clustering characterized by specific protein cluster sizes, depends on the degree of hydrophobic mismatch, on the geometry of the proteins and on the type of lipid bilayer. We observe that proteins with the same degree of mismatch attract each other selectively until a cluster of a specific size is formed and that protein clusters and proteins with a different degree of mismatch repulse each other. In our approach, we demonstrate how simple hydrophobic interactions can lead to a complex collective behaviour. Our results could improve the understanding of several membrane processes in which protein interactions are involved, and they could have important consequences for future drug design.