Lipid redistribution in the highly curved footprint of Piezo1

We investigate the effects on the distribution of lipids in the plasma membrane that are caused by the insertion of a protein, Piezo1, that significantly distorts the membrane toward the cytosol. From coarse-grained molecular dynamics simulations, we find that the major effects occur in the outer, extracellular, leaflet. The mol fraction of cholesterol increases significantly in the curved region of the membrane close to Piezo1, while those of phosphatidylcholine and of sphingomyelin decrease. In the inner leaflet, mol fractions of cholesterol and of phosphatidylethanolamine decrease slightly as the protein is approached, while that of phosphatidylserine increases slightly. The mol fraction of phosphatidylcholine decreases markedly as the protein is approached. Most of these results are understood in the context of a theoretical model that utilizes two elements: 1) a coupling between the leaflets' actual curvatures and their compositionally dependent spontaneous curvatures and 2) the dependence of the spontaneous curvatures not only on the mol fractions of the phospholipids, but also on the effect that cholesterol has on the spontaneous curvatures of the phospholipids.