Realistic Cell Membranes

mitochondrion-molecular-resolution2.jpgBiomembranes are essential cellular components. Together with membrane-adhered structures, such as the cytoskeleton, cell membranes constitute incredibly heterogeneous and crowded environments, containing hundreds of different lipid types and being densely packed with a large variety of membrane proteins. They provide identity not only to the cell as a whole, through the enveloping plasma membrane, but also to many internal organelles.

The Martini model is highly suited to capture the complexity of such cell membranes, as recently reviewed in [1]. Available tools such as Insane [2] and Charmm-GUI [3,4] facilitate setting up cell membranes with arbitrary complex compositions. Current highlights include the >60 lipid mixture representing mammalian plasma membranes [5-7], mixtures of galactolipids modeling the thylakoid membranes [8], the membranes of an enitre mitochondrion with realistic composition as well as shape [9, see Figure], and multi-component bacterial membranes [10].

The ability to simulate membranes with realistic lipid compositions is now enabling researchers to study the interaction of a variety of proteins and other compounds with such membranes, e.g. [11-14].

[1] S.J. Marrink, V. Corradi, P.C.T. Souza, H.I. Ingolfsson, D.P. Tieleman, M.S.P. Sansom. Computational Modeling of Realistic Cell Membranes. Chem. Review, 119:6184–6226, 2019. doi:10.1021/acs.chemrev.8b00460

[2] T.A. Wassenaar, H.I. Ingólfsson, R.A. Böckmann, D.P. Tieleman, S.J. Marrink. Computational lipidomics with insane: a versatile tool for generating custom membranes for molecular simulations. JCTC, 11:2144–2155, 2015. abstract

[3] Y. Qi, H.I. Ingólfsson, X. Cheng, J. Lee, S.J. Marrink, W. Im. CHARMM-GUI Martini Maker for coarse-grained simulations with the Martini force field. JCTC, 11:4486–4494, 2015. abstract

[4] P.C. Hsu, B.M.H. Bruininks, D. Jefferies, P.C. Telles de Souza, J. Lee, D.S. Patel, S.J .Marrink, Y. Qi, S. Khalid, W. Im. CHARMM‐GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides. J. Comput. Chem., 38:2354–2363, 2017. abstract

[5] H.I. Ingólfsson, M.N. Melo, F.J. van Eerden, C. Arnarez, C.A. López, T.A. Wassenaar, X. Periole, A.H. De Vries, D.P. Tieleman, S.J. Marrink. Lipid organization of the plasma membrane. JACS, 136:14554-14559, 2014. open access

[6] H.I. Ingólfsson, T.S. Carpenter, H. Bhatia, P.T. Bremer, S.J. Marrink, F.C. Lightstone. Computational Lipidomics of the Neuronal Plasma Membrane. Biophys. J. 113:2271–2280, 2017. open access

[7] S. Thallmair, H.I. Ingólfsson, S.J. Marrink. Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models. J. Phys. Chem. Lett. 9:5527–5533, 2018. doi:10.1021/acs.jpclett.8b01877

[8] F.J. van Eerden, D.H. de Jong, A.H de Vries, T.A. Wassenaar, S.J. Marrink. Characterization of thylakoid lipid membranes from cyanobacteria and higher plants by molecular dynamics simulations. BBA Biomembranes, 1848:1319–1330, 2015. abstract

[9] W. Pezeshkian, M. Konig, T.A. Wassenaar, S.J. Marrink. Backmapping triangulated surfaces to coarse-grained membrane models. Nature Commun. 11:2296, 2020.

[10] P.C. Hsu, F. Samsudin, J. Shearer, S. Khalid. It Is Complicated: Curvature, Diffusion, and Lipid Sorting within the Two Membranes of Escherichia coli. JPC-Lett. 8 (22), 5513-5518, 2017.

[11] V. Corradi, E. Mendez-Villuendas, H.I. Ingólfsson, R.X. Gu, I. Siuda, M.N. Melo, A. Moussatova, L.J. DeGagné, B.I. Sejdiu, G. Singh, T.A. Wassenaar, K. Delgado Magnero, S.J. Marrink, D.P. Tieleman. Lipid–Protein Interactions Are Unique Fingerprints for Membrane Proteins. ACS Central Science 4:709–717, 2018. doi:10.1021/acscentsci.8b00143

[12] S. Thallmair, P.A. Vainikka, S.J. Marrink. Lipid Fingerprints and Cofactor Dynamics of Light-Harvesting Complex II in Different Membranes. Biophys. J., 116:1446-1455, 2019. doi:10.1016/j.bpj.2019.03.009

[13] J. Shearer, D. Jefferies, S .Khalid. Outer membrane proteins OmpA, FhuA, OmpF, EstA, BtuB, and OmpX have unique lipopolysaccharide fingerprints. J. Chemical Theory and Computation 15 (4), 2608-2619, 2019.

[14] A. Buyan, C.D. Cox, J. Barnoud, J. Li, H.S.M. Chan, B. Martinac, S.J. Marrink, B. Corry. Piezo1 forms specific, functionally important interactions with phosphoinositides and cholesterol. Biophys. J. 119:1683-1697, 2020. doi.10.1016/j.bpj.2020.07.043