Cell membranes contain a large number of different lipid species. Such a multicomponent mixture exhibits a complex phase behavior with regions of structural and compositional heterogeneity. Domains formed in ternary mixtures composed of saturated and unsaturated lipids together with cholesterol have received a lot of attention as they may resemble raft formation in real cells.
We are using MARTINI to assess the molecular nature of these domains at the nano- and mesoscales, information that has thus far eluded experimental determination. We are able to simulate the spontaneous separation of a saturated phosphatidylcholine (PC)/unsaturated PC/cholesterol mixture into a liquid-ordered and a liquid-disordered phase with structural and dynamic properties closely matching experimental data. The near-atomic resolution of the simulations reveals remarkable features of both domains and the boundary domain interface [1-3,8], as well as on the sorting and clustering of model transmembrane proteins in such a domain segregated membrane [4,5,9]. In addition, the properties of binary lipid/cholesterol mixtures have also been addressed [6,7].
The size- and timescales of simulations of raft formation recently got boosted by the introduction of the implicit-solvent Martini model, or Dry Martini . Domain segregation is observed in Dry Martini under the same conditions as it occurs for the regular model, at a severalfold speedup in performance.
 H.J. Risselada, S.J. Marrink. The molecular face of lipid rafts in model membranes. PNAS, 105:17367-17372, 2008. open access
 T. Apajalahti, P. Niemela, P.N. Govindan, M. Miettinen, E. Salonen, S.J. Marrink, I. Vattulainen. Concerted diffusion of lipids in raft-like membranes. Farad. Discuss., 144:411-430, 2010. abstract
 N. Kucerka, D. Marquardt, T.A. Harroun, M.P. Nieh, S.R. Wassall, D.H. de Jong, L.V. Schaefer, S.J. Marrink, J. Katsaras. Cholesterol in bilayers with PUFA chains: Doping with DMPC or POPC results in sterol reorientation and membrane-domain formation. Biochemistry, 49:7485-7493, 2010. abstract
 L.V. Schafer, D.H. de Jong, A. Holt, A.J. Rzepiela, A.H. de Vries, B. Poolman, J.A. Killian, S.J. Marrink. Lipid packing drives the segregation of transmembrane helices into disordered lipid domains in model biomembranes. PNAS, 108:1343-1348, 2011. open access
 J. Domanski, S.J. Marrink, L.V. Schaefer. Transmembrane helices can induce domain formation in crowded model biomembranes. BBA Biomembr., 1818:984-994, 2012. abstract
 W.F.D. Bennett, J.L. MacCallum, M.J. Hinner, S.J. Marrink, D.P. Tieleman. A molecular view of cholesterol flip-flop and chemical potential in different membrane environments. JACS, 131:12714-12720, 2009. abstract
 S.J. Marrink, A.H. de Vries, T.A. Harroun, J. Katsaras, S.R. Wassall. Cholesterol shows preference for the interior of polyunsaturated lipid membranes. JACS, 130:10-11, 2008. abstract
 H.J. Risselada, S.J. Marrink, M. Muller. Curvature-dependent elastic properties of liquid-ordered domains result in inverted domain sorting on uniaxially compressed vesicles. Phys. Rev. Lett., 106:148102, 2011. abstract
 D.H. de Jong, C.A. Lopez, S.J. Marrink. Molecular view on protein sorting into liquid-ordered membrane domains mediated by gangliosides and lipid anchors. Farad. Discuss., 161:347-363, 2013. abstract
 C. Arnarez, J.J. Uusitalo, M.F. Masman, H.I. Ingolfsson, D.H. de Jong, M.N. Melo, X. Periole, A.H. de Vries, S.J. Marrink. Dry Martini: coarse grained implicit water force field for (bio)molecular simulations. J. Chem. Theory Comput., 11:260-275, 2015. abstract
|Last modified:||28 January 2019 4.25 p.m.|