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NaCl Interactions with Phosphatidylcholine Bilayers Do Not Alter Membrane Structure but Induce Long-Range Ordering of Ions and Water

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Abstract

It is generally accepted that ions interact directly with lipids in biological membranes. Decades of biophysical studies on pure lipid bilayer systems have shown that only certain types of ions, most significantly large anions and multivalent cations, can fundamentally alter the structure and dynamics of lipid bilayers. It has long been accepted that at physiological concentrations NaCl ions do not alter the physical behavior or structure of bilayers composed solely of zwitterionic phosphatidylcholine (PC) lipids. Recent X-ray scattering experiments have reaffirmed this dogma, showing that below 1 M concentration, NaCl does not significantly alter bilayer structure. However, despite this history, there is an ongoing controversy within the molecular dynamics (MD) simulation community regarding NaCl/PC interactions. In particular, the CHARMM and GROMOS force fields show dramatically different behavior, including the effect on bilayer structure, surface potential, and the ability to form stable, coordinated ion–lipid complexes. Here, using long-timescale, constant-pressure simulations under the newest version of the CHARMM force field, we find that Na+ and Cl− associate with PC head groups in a POPC bilayer with approximately equal, though weak, affinity, and that the salt has a negligible effect on bilayer structure, consistent with earlier CHARMM results and more recent X-ray data. The results suggest that interpretation of simulations where lipids interact with charged groups of any sort, including charged proteins, must be carefully scrutinized.

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References

  • Bangham AD (1968) Membrane models with phospholipids. Prog Biophys Mol Biol 18:29–95

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Bockmann RA, Grubmuller H (2004) Multistep binding of divalent cations to phospholipid bilayers: a molecular dynamics study. Angew Chem Int Ed Engl 43:1021–1024

    Article  PubMed  Google Scholar 

  • Bockmann RA, Hac A, Heimburg T, Grubmuller H (2003) Effect of sodium chloride on a lipid bilayer. Biophys J 85:1647–1655

    Article  PubMed  Google Scholar 

  • Brooks BR, Brooks CL 3rd, Mackerell AD Jr, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M (2009) CHARMM: the biomolecular simulation program. J Comput Chem 30:1545–1614

    Article  PubMed  CAS  Google Scholar 

  • Clarke RJ, Lupfert C (1999) Influence of anions and cations on the dipole potential of phosphatidylcholine vesicles: a basis for the Hofmeister effect. Biophys J 76:2614–2624

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Cunningham BA, Gelerinter E, Lis LJ (1988) Monovalent ion–phosphatidylcholine interactions: an electron paramagnetic resonance study. Chem Phys Lipids 46:205–211

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg M, Gresalfi T, Riccio T, McLaughlin S (1979) Adsorption of monovalent cations to bilayer membranes containing negative phospholipids. Biochemistry 18:5213–5223

    Article  PubMed  CAS  Google Scholar 

  • Grossfield A, Zuckerman DM (2009) Quantifying uncertainty and sampling quality in biomolecular simulations. Annu Rep Comput Chem 5:23–48

    Article  PubMed  CAS  Google Scholar 

  • Gurtovenko AA (2005) Asymmetry of lipid bilayers induced by monovalent salt: atomistic molecular-dynamics study. J Chem Phys 122:244902

    Article  PubMed  Google Scholar 

  • Hanai T, Haydon DA, Taylor J (1965) Polar group orientation and the electrical properties of lecithin bimolecular leaflets. J Theor Biol 9:278–296

    Article  PubMed  CAS  Google Scholar 

  • Khavrutskii IV, Gorfe AA, Lu B, McCammon JA (2009) Free energy for the permeation of Na(+) and Cl(−) ions and their ion-pair through a zwitterionic dimyristoyl phosphatidylcholine lipid bilayer by umbrella integration with harmonic Fourier beads. J Am Chem Soc 131:1706–1716

    Article  PubMed  CAS  Google Scholar 

  • Klauda JB, Venable RM, Freites JA, O’Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD Jr, Pastor RW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114:7830–7843

    Article  PubMed  CAS  Google Scholar 

  • Lee SJ, Song Y, Baker NA (2008) 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 94:3565–3576

    Article  PubMed  CAS  Google Scholar 

  • Loosley-Millman ME, Rand RP, Parsegian VA (1982) Effects of monovalent ion binding and screening on measured electrostatic forces between charged phospholipid bilayers. Biophys J 40:221–232

    Article  PubMed  CAS  Google Scholar 

  • Macdonald PM, Seelig J (1988) Anion binding to neutral and positively charged lipid membranes. Biochemistry 27:6769–6775

    Article  PubMed  CAS  Google Scholar 

  • McDaniel RV, McLaughlin A, Winiski AP, Eisenberg M, McLaughlin S (1984) Bilayer membranes containing the ganglioside GM1: models for electrostatic potentials adjacent to biological membranes. Biochemistry 23:4618–4624

    Article  PubMed  CAS  Google Scholar 

  • Pabst G, Hodzic A, Strancar J, Danner S, Rappolt M, Laggner P (2007) Rigidification of neutral lipid bilayers in the presence of salts. Biophys J 93:2688–2696

    Article  PubMed  CAS  Google Scholar 

  • Pandit SA, Bostick D, Berkowitz ML (2003) Molecular dynamics simulation of a dipalmitoylphosphatidylcholine bilayer with NaCl. Biophys J 84:3743–3750

    Article  PubMed  CAS  Google Scholar 

  • Parsegian VA, Fuller N, Rand RP (1979) Measured work of deformation and repulsion of lecithin bilayers. Proc Natl Acad Sci USA 76:2750–2754

    Article  PubMed  CAS  Google Scholar 

  • Petrache HI, Tristram-Nagle S, Gawrisch K, Harries D, Parsegian VA, Nagle JF (2004) Structure and fluctuations of charged phosphatidylserine bilayers in the absence of salt. Biophys J 86:1574–1586

    Article  PubMed  CAS  Google Scholar 

  • Petrache HI, Kimchi I, Harries D, Parsegian VA (2005) Measured depletion of ions at the biomembrane interface. J Am Chem Soc 127:11546–11547

    Article  PubMed  CAS  Google Scholar 

  • Petrache HI, Zemb T, Belloni L, Parsegian VA (2006) Salt screening and specific ion adsorption determine neutral-lipid membrane interactions. Proc Natl Acad Sci USA 103:7982–7987

    Article  PubMed  CAS  Google Scholar 

  • Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26:1781–1802

    Article  PubMed  CAS  Google Scholar 

  • Roux M, Bloom M (1990) Ca2+, Mg2+, Li+, Na+, and K+ distributions in the headgroup region of binary membranes of phosphatidylcholine and phosphatidylserine as seen by deuterium NMR. Biochemistry 29:7077–7089

    Article  PubMed  CAS  Google Scholar 

  • Roux B, Luo Y (2010) Simulation of osmotic pressure in concentrated aqueous salt solutions. J Phys Chem Lett 1:183–189

    Article  Google Scholar 

  • Rydall JR, Macdonald PM (1992) Investigation of anion binding to neutral lipid membranes using 2H NMR. Biochemistry 31:1092–1099

    Article  PubMed  CAS  Google Scholar 

  • Sachs JN, Woolf TB (2003) Understanding the Hofmeister effect in interactions between chaotropic anions and lipid bilayers: molecular dynamics simulations. J Am Chem Soc 125:8742–8743

    Article  PubMed  CAS  Google Scholar 

  • Sachs JN, Petrache HI, Woolf TB (2003) Interpretation of small angle X-ray measurements guided by molecular dynamics simulations of lipid bilayers. Chem Phys Lipids 126:211–223

    Article  PubMed  CAS  Google Scholar 

  • Sachs JN, Nanda H, Petrache HI, Woolf TB (2004) Changes in phosphatidylcholine headgroup tilt and water order induced by monovalent salts: molecular dynamics simulations. Biophys J 86:3772–3782

    Article  PubMed  CAS  Google Scholar 

  • Szekely O, Steiner A, Szekely P, Amit E, Asor R, Tamburu C, Raviv U (2011) The structure of ions and zwitterionic lipids regulates the charge of dipolar membranes. Langmuir 27:7419–7438

    Article  PubMed  CAS  Google Scholar 

  • Tatulian SA (1987) Binding of alkaline-earth metal cations and some anions to phosphatidylcholine liposomes. Eur J Biochem 170:413–420

    Article  PubMed  CAS  Google Scholar 

  • Vacha R, Siu SW, Petrov M, Bockmann RA, Barucha-Kraszewska J, Jurkiewicz P, Hof M, Berkowitz ML, Jungwirth P (2009) Effects of alkali cations and halide anions on the DOPC lipid membrane. J Phys Chem A 113:7235–7243

    Article  PubMed  CAS  Google Scholar 

  • van Buuren AR, Marrink SJ, Berendsen HJ (1993) A molecular dynamics study of the decane/water interface. J Phys Chem 97:9206–9212

    Article  Google Scholar 

  • Winiski AP, McLaughlin AC, McDaniel RV, Eisenberg M, McLaughlin S (1986) An experimental test of the discreteness-of-charge effect in positive and negative lipid bilayers. Biochemistry 25:8206–8214

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the Minnesota Supercomputing Institute for computational resources, B. Roux, and R. Pastor for valuable discussion, and A. Grossfield for discussion regarding error estimation.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA

    Christopher C. Valley, Jason D. Perlmutter, Anthony R. Braun & Jonathan N. Sachs

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  1. Christopher C. Valley
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  2. Jason D. Perlmutter
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  3. Anthony R. Braun
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  4. Jonathan N. Sachs
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Correspondence to Jonathan N. Sachs.

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Valley, C.C., Perlmutter, J.D., Braun, A.R. et al. NaCl Interactions with Phosphatidylcholine Bilayers Do Not Alter Membrane Structure but Induce Long-Range Ordering of Ions and Water. J Membrane Biol 244, 35–42 (2011). https://doi.org/10.1007/s00232-011-9395-1

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