Effect of Asymmetry on Bilayer Membrane Systems

Abstract

Many biological processes, such as membrane fusion and the action of microbial proteins, involve asymmetric uptake of proteins. In addition, it has been demonstrated that large mechaosensitive channels open by the asymmetric inclusion of lyso-lipids in the bilayer in the absence of external pressure. These phenomena can be interpreted in terms of the asymmetric local pressure profile in the bilayer, which lacks the quantitative understanding. By noting that such asymmetric pressure profile can be induced in bilayer membranes with asymmetric number of lipids between leaflets, to provide quantitative understanding, we performed molecular dynamics simulations of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) bilayer membranes for a set of systems with different level of asymmetry with and without gramicidin A (gA) or WALP23. We observed that even highly asymmetric lipid bilayers with and without gA or WALP23 were stable during the whole simulation time, which is consistent with the previous study of dipalmitoyl-phosphatidylcholine (DPPC) bilayers [J. Am. Chem. Soc. 131, 15194 (2009)]. As the number of lipids in the lower leaflet becomes smaller, the lipids are more tightly packed in the top leaflet and less ordered in the bottom leaflet, which are quantified in terms the lateral pressure profile, the order parameter, the area per lipid, etc. However, the hydrophobic thickness for pure lipid bilayers does not show meaningful dependence on the asymmetry, which results from the stretched and less ordered lipids in the upper and lower leaflets, respectively. We will also discuss the influence of the asymmetry on the properties of protein-lipid interactions, such as the distance dependence of the lipid properties and the interaction patterns around gA or WALP23.