(205b) Mesoscopic Simulation Study of Lipid-Mediated Interactions between Intrinsic Membrane Proteins

Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may play an important role in the decision of the protein topology after insertion in the membrane, in regulating the protein activity, in aggregation of misfolded proteins and in signal transduction. To gain insight into the lipid-mediated interactions between intrinsic membrane proteins, we developed a mesoscopic model of a lipid bilayer with embedded proteins, which we studied with dissipative particle dynamics. Our calculations of the potential of mean force between transmembrane proteins show that hydrophobic forces drive long range protein-protein interactions whose nature depends on the length of the protein hydrophobic segment, on the three dimensional structure of the protein and on the properties of the lipid bilayer. The observed protein interactions are found to occur spontaneously during the search of the system for an optimal hydrophilic shielding of the protein and lipid hydrophobic parts, within the constraint of the flexibility of the components. To study the clustering properties of the proteins we switched to a two-dimensional model of the lipid bilayer in which proteins interact via the computed potential of mean forces. Under mismatch conditions cluster formation takes place, with the cluster size exhibiting an upper limit.