Peter Tieleman

Lipid Organization of the Plasma Membrane

The detailed organization of cellular membranes remains rather elusive. In this lecture, I provide a high-resolution view of the lipid organization of a plasma membrane (PM) that is based on large-scale molecular dynamics simulations using the Martini force field [1]. Our mammalian PM model consists of 63 different lipid species, combining 14 types of headgroups and 11 types of tails asymmetrically distributed across the two leaflets [2]. The complexity of the PM mixture gives rise to an enrichment of cholesterol in the outer leaflet and a general non-ideal lateral mixing of the different lipid species. Transient domains with liquid-ordered character form and disappear on the microsecond time scale. These domains are coupled across the two membrane leaflets. In the outer leaflet, distinct nanodomains consisting of gangliosides are observed. Additional simulations of membrane proteins embedded in the PM reveal preferential interactions with specific lipids. The in-silico data provide a key view on the lateral organization of lipids and proteins in one of lifes fundamental structures, the cell membrane.[1] S.J. Marrink, D.P. Tieleman. Perspective on the Martini model. Chem. Soc. Rev., 42:6801-6822, 2013.[2] H.I. Ingolfsson, M.N. Melo, F.J. van Eerden, C. Arnarez, C.A. Lopez, T.A. Wassenaar, X. Periole, A.H. De Vries, D.P. Tieleman, S.J. Marrink. Lipid organization of the plasma membrane. JACS, 2014. http://dx.doi.org/10.1021/ja507832e