Molecular simulation of the effect of cholesterol on lipid-mediated protein-protein interactions.
Experiments and molecular simulations have shown that the hydrophobic mismatch between proteins and membranes contributes significantly to lipid-mediated protein-protein interactions. In this article, we discuss the effect of cholesterol on lipid-mediated protein-protein interactions as function of hydrophobic mismatch, protein diameter and protein cluster size, lipid tail length, and temperature. To do so, we study a mesoscopic model of a hydrated bilayer containing lipids and cholesterol in which proteins are embedded, with a hybrid dissipative particle dynamics-Monte Carlo method. We propose a mechanism by which cholesterol affects protein interactions: protein-induced, cholesterol-enriched, or cholesterol-depleted lipid shells surrounding the proteins affect the lipid-mediated protein-protein interactions. Our calculations of the potential of mean force between proteins and protein clusters show that the addition of cholesterol dramatically reduces repulsive lipid-mediated interactions between proteins (protein clusters) with positive mismatch, but does not affect attractive interactions between proteins with negative mismatch. Cholesterol has only a modest effect on the repulsive interactions between proteins with different mismatch.
Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California, USA. frederick.demeyer@yahoo.com
Frédérick J-M
FJ
de Meyer
Jocelyn M
JM
Rodgers
Thomas F
TF
Willems
Berend
B
Smit
D002784:Cholesterol / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D044367:Phase Transition / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects
D008051:Lipid Bilayers; D002784:Cholesterol