We present molecular dynamics simulations of a multicomponent, asymmetric bilayer in mixed aqueous solutions of sodium and potassium chloride. Because of the geometry of the system, there are two aqueous solution regions in our simulations: one mimics the intracellular region, and one mimics the extracellular region. Ion-specific effects are evident at the membrane/aqueous solution interface. Namely, at equal concentrations of sodium and potassium, sodium ions are more strongly adsorbed to carbonyl groups of the lipid headgroups. A significant concentration excess of potassium is needed for this ion to overwhelm the sodium abundance at the membrane. Ion-membrane interactions also lead to concentration-dependent and cation-specific behavior of the electrostatic potential in the intracellular region because of the negative charge on the inner leaflet. In addition, water permeation across the membrane was observed on a timescale of approximately 100 ns. This study represents a step toward the modeling of realistic biological membranes at physiological conditions in intracellular and extracellular environments.

Institute of Organic Chemistry and Biochemistry Academy of Sciences of Czech Republic and Center for Biomolecules and Complex Molecular Systems 16610 Prague 6 Czech Republic

Zobrazit více v PubMed

Alberts B., Johnson A., Lewis J., Raff M., Roberts K. Garland Science; New York: 2002. Molecular Biology of the Cell.

Parthasarathy R., Groves J.T. Curvature and spatial organization in biological membranes. Soft Matter. 2007;3:24–33. PubMed

Simons K., Ikonen E. Functional rafts in cell membranes. Nature. 1997;387:569–572. PubMed

Pike L.J. Rafts defined: a report on the keystone symposium on lipid rafts and cell function. J. Lipid Res. 2006;47:1597–1598. PubMed

Epand R.M. Proteins and cholesterol-rich domains. Biochim. Biophys. Acta. 2008;1778:1576–1582. PubMed

Devaux P.F., Morris R. Transmembrane asymmetry and lateral domains in biological membranes. Traffic. 2004;5:241–246. PubMed

Aroti A., Leontidis E., Dubois M., Zemb T. Effects of monovalent anions of the Hofmeister series on DPPC lipid bilayers part I: swelling and in-plane equations of state. Biophys. J. 2007;93:1580–1590. PubMed PMC

Leontidis E., Aroti A., Belloni L., Dubois M., Zemb T. Effects of monovalent anions of the Hofmeister series on DPPC lipid bilayers part II: modeling the perpendicular and lateral equation-of-state. Biophys. J. 2007;93:1591–1607. PubMed PMC

Garcia-Celma J.J., Hatahet L., Kunz W., Fendler K. Specific anion and cation binding to lipid membranes investigated on a solid supported membrane. Langmuir. 2007;23:10074–10080. PubMed

Garcia-Manyes S., Oncins G., Sanz F. Effect of temperature on the nanomechanics of lipid bilayers studied by force spectroscopy. Biophys. J. 2005;89:4261–4274. PubMed PMC

Lee S.J., Song Y., Baker N.A. Molecular dynamics simulations of asymmetric NaCl and KCl solutions separated by phosphatidylcholine bilayers: potential drops and structural changes induced by strong Na+-lipid interactions and finite size effects. Biophys. J. 2008;94:3565–3576. PubMed PMC

Gurtovenko A.A., Vattulainen I. Lipid transmembrane asymmetry and intrinsic membrane potential: two sides of the same coin. J. Am. Chem. Soc. 2007;129:5358–5359. PubMed

Gurtovenko A.A., Vattulainen I. Effect of NaCl and KCl on phosphatidylcholine and phosphatidylethanolamine lipid membranes: insight from atomic-scale simulations for understanding salt-induced effects in the plasma membrane. J. Phys. Chem. B. 2008;112:1953–1962. PubMed

Berkowitz M.L., Bostick D.L., Pandit S. Aqueous solutions next to phospholipid membrane surfaces: Insights from simulations. Chem. Rev. 2006;106:1527–1539. PubMed

Virtanen J.A., Cheng K.H., Somerharju P. Phospholipid composition of the mammalian red cell membrane can be rationalized by a superlattice model. Proc. Natl. Acad. Sci. USA. 1998;95:4964–4969. PubMed PMC

Zachowski A. Phospholipids in animal eukaryotic membranes—transverse asymmetry and movement. Biochem. J. 1993;294:1–14. PubMed PMC

Tieleman D.P., Sansom M.S.P., Berendsen H.J.C. Alamethicin helices in a bilayer and in solution: molecular dynamics simulations. Biophys. J. 1999;76:40–49. PubMed PMC

Berger O., Edholm O., Jahnig F. Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys. J. 1997;72:2002–2013. PubMed PMC

Tieleman D.P., Berendsen H.J.C. A molecular dynamics study of the pores formed by Escherichia coli OmpF porin in a fully hydrated palmitoyloleoylphosphatidylcholine bilayer. Biophys. J. 1998;74:2786–2801. PubMed PMC

Mukhopadhyay P., Monticelli L., Tieleman D.P. Molecular dynamics simulation of a palmitoyl-oleoyl phosphatidylserine bilayer with Na+ counterions and NaCl. Biophys. J. 2004;86:1601–1609. PubMed PMC

Bockmann R.A., Hac A., Heimburg T., Grubmuller H. Effect of sodium chloride on a lipid bilayer. Biophys. J. 2003;85:1647–1655. PubMed PMC

Niemela P., Hyvonen M.T., Vattulainen I. Structure and dynamics of sphingomyelin bilayer: insight gained through systematic comparison to phosphatidylcholine. Biophys. J. 2004;87:2976–2989. PubMed PMC

Berendsen H.J.C., Vanderspoel D., Vandrunen R. GROMACS—a message-passing parallel molecular-dynamics implementation. Comput. Phys. Commun. 1995;91:43–56.

Lindahl E., Hess B., van der Spoel D. GROMACS 3.0: a package for molecular simulation and trajectory analysis. J. Mol. Model. 2001;7:306–317.

Darden T., York D., Pedersen L. Particle mesh Ewald—an N.LOG(N) method for Ewald sums in large systems. J. Chem. Phys. 1993;98:10089–10092.

Miyamoto S., Kollman P.A. SETTLE—an analytical version of the SHAKE and RATTLE algorithm for rigid water models. J. Comput. Chem. 1992;13:952–962.

Hess B., Bekker H., Berendsen H.J.C., Fraaije J. LINCS: a linear constraint solver for molecular simulations. J. Comput. Chem. 1997;18:1463–1472.

Berendsen H.J.C., Grigera J.R., Straatsma T.P. The missing term in effective pair potentials. J. Phys. Chem. 1987;91:6269–6271.

Gurtovenko A.A., Vattulainen I. Ion leakage through transient water pores in protein-free lipid membranes driven by transmembrane ionic charge imbalance. Biophys. J. 2007;92:1878–1890. PubMed PMC

Dang L.X., Schenter G.K., Glezakou V.A., Fulton J.L. Molecular simulation analysis and x-ray absorption measurement of Ca2+, K+ and Cl− ions in solution. J. Phys. Chem. B. 2006;110:23644–23654. PubMed

Sachs J.N., Crozier P.S., Woolf T.B. Atomistic simulations of biologically realistic transmembrane potential gradients. J. Chem. Phys. 2004;121:10847–10851. PubMed

Siu S.W.I., Vácha R., Jungwirth P., Bockmann R.A. Biomolecular simulations of membranes: physical properties from different force fields. J. Chem. Phys. 2008;128:125103. PubMed

Pandit S.A., Bostick D., Berkowitz M.L. Mixed bilayer containing dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine: lipid complexation, ion binding, and electrostatics. Biophys. J. 2003;85:3120–3131. PubMed PMC

Cordomi A., Edholm O., Perez J.J. Effect of ions on a dipalmitoyl phosphatidylcholine bilayer. A molecular dynamics simulation study. J. Phys. Chem. B. 2008;112:1397–1408. PubMed

Jagoda-Cwiklik B., Vácha R., Lund M., Srebro M., Jungwirth P. Ion pairing as a possible clue for discriminating between sodium and potassium in biological and other complex environments. J. Phys. Chem. B. 2007;111:14077–14079. PubMed

Gurtovenko A.A., Vattulainen I. Membrane potential and electrostatics of phospholipid bilayers with asymmetric transmembrane distribution of anionic lipids. J. Phys. Chem. B. 2008;112:4629–4634. PubMed

Mathai J.C., Tristram-Nagle S., Nagle J.F., Zeidel M.L. Structural determinants of water permeability through the lipid membrane. J. Gen. Physiol. 2008;131:69–76. PubMed PMC

Nagle J.F., Mathai J.C., Zeidel M.L., Tristram-Nagle S. Theory of passive permeability through lipid bilayers. J. Gen. Physiol. 2008;131:77–85. PubMed PMC

Shinoda K., Shinoda W., Mikami M. Efficient free energy calculation of water across lipid membranes. J. Comput. Chem. 2008;29:1912–1918. PubMed

Bemporad D., Luttmann C., Essex J.W. Behaviour of small solutes and large drugs in a lipid bilayer from computer simulations. Biochim. Biophys. Acta. 2005;1718:1–21. PubMed

Marrink S.J., Berendsen H.J.C. Simulation of water transport through a lipid-membrane. J. Phys. Chem. 1994;98:4155–4168.

Vrbka L., Vondrasek J., Jagoda-Cwiklik B., Vacha R., Jungwirth P. Quantification and rationalization of the higher affinity of sodium over potassium to protein surfaces. Proc. Natl. Acad. Sci. USA. 2006;103:15440–15444. PubMed PMC

Vácha R., Siu S.W.I., Petrov M., Böckmann R.A., Jurkiewicz P. Effects of alkali cations and halide anions on the DOPC lipid membrane. J. Phys. Chem. B. 2009 In press. PubMed

Reviakine I., Simon A., Brisson A. Effect of Ca2+ on the morphology of mixed DPPC-DOPS supported phospholipid bilayers. Langmuir. 2000;16:1473–1477.

Peptide translocation across asymmetric phospholipid membranes

There Is No Simple Model of the Plasma Membrane Organization