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The Journal of Membrane Biology

, Volume 252, Issue 4–5, pp 241–260 | Cite as

Spontaneous and Stress-Induced Pore Formation in Membranes: Theory, Experiments and Simulations

  • Edel Cunill-Semanat
  • Jesús SalgadoEmail author
Article
Part of the following topical collections:
  1. Membrane and Receptor Dynamics

Abstract

The large plasticity, dynamics and adaptability of biological membranes allow different modes of intrinsic and inducible permeability. These phenomena are of physiological importance for a number of natural functions related to cell death and can also be manipulated artificially for practical purposes like gene transfer, drug delivery, prevention of infections or anticancer therapy. For these advances to develop in a controllable and specific way, we need a sufficient understanding of the membrane permeability phenomena. Since the formulation of early concepts of pore formation, there has been an enormous effort to describe membrane permeability by using theory, simulations and experiments. A major breakthrough has come recently through theoretical developments that allow building continuous trajectories of pore formation both in the absence and presence of stress conditions. The new model provides a coherent quantitative view of membrane permeabilization, useful to test the impact of known lipid properties, make predictions and postulate specific pore intermediates that can be studied by simulations. For example, this theory predicts unprecedented dependencies of the line tension on the pore radius and on applied lateral tension which explain previous puzzling results. In parallel, important concepts have also come from molecular dynamics simulations, of which the role of water for membrane permeabilization is of special interest. These advances open new challenges and perspectives for future progress in the study of membrane permeability, as experiments and simulations will need to test the theoretical predictions, while theory achieves new refinements that provide a physical ground for observations.

Graphic Abstract

Keywords

Lipid pore Line tension Lateral tension Electroporation Single GUV experiments Molecular dynamics simulations 

Notes

Acknowledgements

JS acknowledges support from the Spanish MINECO (BFU2016-76805-P and BFU2017-91559-EXP, financed in part by the European Social Fund—ESF).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Abidor IG, Arakelyan VB, Chernomordik LV, Chizmadzhev YA, Pastushenko VF, Tarasevich MR (1979) Electric breakdown of bilayer lipid membranes I. The main experimental facts and their qualitative discussion. Bioelectrochem Bioenerg 6:37–52.  https://doi.org/10.1016/0302-4598(79)85005-9 CrossRefGoogle Scholar
  2. Afacan NJ, Yeung ATY, Pena OM, Hancock REW (2012) Therapeutic potential of host defense peptides in antibiotic-resistant infections. Curr Pharm Des 18:807–819.  https://doi.org/10.2174/138161212799277617 CrossRefPubMedGoogle Scholar
  3. Akimov SA, Kuzmin PI, Zimmerberg J, Cohen FS (2007) Lateral tension increases the line tension between two domains in a lipid bilayer membrane. Phys Rev E 75(1):011919.  https://doi.org/10.1103/physreve.75.011919 CrossRefGoogle Scholar
  4. Akimov SA, Volynsky PE, Galimzyanov TR, Kuzmin PI, Pavlov KV, Batishchev OV (2017a) Pore formation in lipid membrane I: continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore. Sci Rep 7(1):12152.  https://doi.org/10.1038/s41598-017-12127-7 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Akimov SA, Volynsky PE, Galimzyanov TR, Kuzmin PI, Pavlov KV, Batishchev OV (2017b) Pore formation in lipid membrane II: energy landscape under external stress. Sci Rep 7(1):12509.  https://doi.org/10.1038/s41598-017-12749-x CrossRefPubMedPubMedCentralGoogle Scholar
  6. Awasthi N, Hub JS (2016) Simulations of pore formation in lipid membranes: reaction coordinates, convergence, hysteresis, and finite-size effects. J Chem Theory Comput 12:3261–3269.  https://doi.org/10.1021/acs.jctc.6b00369 CrossRefPubMedGoogle Scholar
  7. Ayuyan AG, Cohen FS (2008) Raft composition at physiological temperature and pH in the absence of detergents. Biophys J 94:2654–2666.  https://doi.org/10.1529/biophysj.107.118596 CrossRefPubMedGoogle Scholar
  8. Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238.  https://doi.org/10.1016/S0022-2836(65)80093-6 CrossRefPubMedGoogle Scholar
  9. Bennett WFD, Tieleman DP (2014) The importance of membrane defects—lessons from simulations. Acc Chem Res 47:2244–2251.  https://doi.org/10.1021/ar4002729 CrossRefPubMedGoogle Scholar
  10. Bennett WFD, Sapay N, Tieleman DP (2014) Atomistic simulations of pore formation and closure in lipid bilayers. Biophys J 106:210–219.  https://doi.org/10.1016/j.bpj.2013.11.4486 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Böckmann RA, de Groot BL, Kakorin S, Neumann E, Grubmüller H (2008) Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations. Biophys J 95:1837–1850.  https://doi.org/10.1529/biophysj.108.129437 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Brochard-Wyart F, de Gennes PG, Sandre O (2000) Transient pores in stretched vesicles: role of leak-out. Phys A 278:32–51.  https://doi.org/10.1016/S0378-4371(99)00559-2 CrossRefGoogle Scholar
  13. Chernomordik LV, Kozlov MM, Melikyan GB, Abidor IG, Markin VS, Chizmadzhev YA (1985) The shape of lipid molecules and monolayer membrane fusion. Biochim Biophys Acta 812:643–655.  https://doi.org/10.1016/0005-2736(85)90257-3 CrossRefGoogle Scholar
  14. Deamer D (2016) Membranes and the origin of life: a century of conjecture. J Mol Evol 83:159–168.  https://doi.org/10.1007/s00239-016-9770-8 CrossRefPubMedGoogle Scholar
  15. Deryagin B, Gutop YV (1962) Theory of the breakdown (rupture) of free films. Kolloidn Zh 24:370–374Google Scholar
  16. Esteban-Martín S, Salgado J (2007) Self-assembling of peptide/membrane complexes by atomistic molecular dynamics simulations. Biophys J 92:903–912.  https://doi.org/10.1529/biophysj.106.093013 CrossRefPubMedGoogle Scholar
  17. Esteban-Martín S, Risselada HJ, Salgado J, Marrink SJ (2009) Stability of asymmetric lipid bilayers assessed by molecular dynamics simulations. J Am Chem Soc 131:15194–15202.  https://doi.org/10.1021/ja904450t CrossRefPubMedGoogle Scholar
  18. Evans E, Smith BA (2011) Kinetics of hole nucleation in biomembrane rupture. New J Phys 13:095010.  https://doi.org/10.1088/1367-2630/13/9/095010 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Evans E, Heinrich V, Ludwig F, Rawicz W (2003) Dynamic tension spectroscopy and strength of biomembranes. Biophys J 85:2342–2350.  https://doi.org/10.1016/S0006-3495(03)74658-X CrossRefPubMedPubMedCentralGoogle Scholar
  20. Fuertes G, García-Sáez AJ, Esteban-Martín S, Giménez D, Sánchez-Muñoz OL, Schwille P, Salgado J (2010) Pores formed by Baxα5 relax to a smaller size and keep at equilibrium. Biophys J 99:2917–2925.  https://doi.org/10.1016/j.bpj.2010.08.068 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Fuertes G, Giménez D, Esteban-Martín S, Sánchez-Muñoz OL, Salgado J (2011) A lipocentric view of peptide-induced pores. Eur Biophys J 40:399–415.  https://doi.org/10.1007/s00249-011-0693-4 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Galimzyanov TR, Molotkovsky RJ, Bozdaganyan ME, Cohen FS, Pohl P, Akimov SA (2015) Elastic membrane deformations govern interleaflet coupling of lipid-ordered domains. Phys Rev Lett 115:088101.  https://doi.org/10.1103/physrevlett.115.088101 CrossRefPubMedPubMedCentralGoogle Scholar
  23. García-Sáez AJ, Chiantia S, Salgado J, Schwille P (2007) Pore formation by a Bax-derived peptide: effect on the line tension of the membrane probed by AFM. Biophys J 93:103–112.  https://doi.org/10.1529/biophysj.106.100370 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Glaser RW, Leikin SL, Chernomordik LV, Pastushenko VF, Sokirko AI (1988) Reversible electrical breakdown of lipid bilayers: formation and evolution of pores. Biochim Biophys Acta 940:275–287CrossRefGoogle Scholar
  25. Green DR, Reed JC (1998) Mitochondria and Apoptosis. Science 281:1309–1312.  https://doi.org/10.1126/science.281.5381.1309 CrossRefPubMedGoogle Scholar
  26. Guha S, Ghimire J, Wu E, Wimley WC (2019) Mechanistic landscape of membrane-permeabilizing peptides. Chem Rev 119(9):6040–6085.  https://doi.org/10.1021/acs.chemrev.8b00520 CrossRefPubMedGoogle Scholar
  27. Gurtovenko AA, Vattulainen I (2005) Pore formation coupled to ion transport through lipid membranes as induced by transmembrane ionic charge imbalance: atomistic molecular dynamics study. J Am Chem Soc 127:17570–17571.  https://doi.org/10.1021/ja053129n CrossRefPubMedGoogle Scholar
  28. Gurtovenko AA, Anwar J, Vattulainen I (2010) Defect-mediated trafficking across cell membranes: insights fromin silicomodeling. Chem Rev 110:6077–6103.  https://doi.org/10.1021/cr1000783 CrossRefPubMedGoogle Scholar
  29. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100.  https://doi.org/10.1007/BF00656997 CrossRefPubMedGoogle Scholar
  30. Hamm M, Kozlov MM (2000) Elastic energy of tilt and bending of fluid membranes. Eur Phys J E 3:323–335.  https://doi.org/10.1007/s101890070003 CrossRefGoogle Scholar
  31. Haney, E.F., Straus, S.K., Hancock, R.E.W., 2019. Reassessing the Host Defense Peptide Landscape. Frontiers in Chemistry 7.  https://doi.org/10.3389/fchem.2019.00043
  32. Helfrich W (1973) Elastic properties of lipid bilayers: theory and possible experiments. Z Naturforsch C 28:693–703CrossRefGoogle Scholar
  33. Hovakeemian SG, Liu R, Gellman SH, Heerklotz H (2015) Correlating antimicrobial activity and model membrane leakage induced by nylon-3 polymers and detergents. Soft Matter 11:6840–6851.  https://doi.org/10.1039/c5sm01521a CrossRefPubMedPubMedCentralGoogle Scholar
  34. Huang HW, Charron NE (2017) Understanding membrane-active antimicrobial peptides. Quart Rev Biophys 50:e10.  https://doi.org/10.1017/s0033583517000087 CrossRefGoogle Scholar
  35. Huang HW, Chen F-Y, Lee M-T (2004) Molecular mechanism of Peptide-induced pores in membranes. Phys Rev Lett 92:198304CrossRefGoogle Scholar
  36. Karal MAS, Yamazaki M (2015) Communication: activation energy of tension-induced pore formation in lipid membranes. J. Chem. Phys 143:081103.  https://doi.org/10.1063/1.4930108 CrossRefPubMedGoogle Scholar
  37. Karal MAS, Alam JM, Takahashi T, Levadny V, Yamazaki M (2015) Stretch-activated pore of the antimicrobial peptide, Magainin 2. Langmuir 31:3391–3401.  https://doi.org/10.1021/la503318z CrossRefPubMedGoogle Scholar
  38. Karal MAS, Levadnyy V, Yamazaki M (2016) Analysis of constant tension-induced rupture of lipid membranes using activation energy. Phys Chem Chem Phys 18:13487–13495.  https://doi.org/10.1039/c6cp01184e CrossRefPubMedGoogle Scholar
  39. Karatekin E, Sandre O, Guitouni H, Borghi N, Puech P-H, Brochard-Wyart F (2003) Cascades of transient pores in giant vesicles: line tension and transport. Biophys J 84:1734–1749.  https://doi.org/10.1016/S0006-3495(03)74981-9 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Kelly GJ, Kia AF-A, Hassan F, O’Grady S, Morgan MP, Creaven BS, McClean S, Harmey JH, Devocelle M (2016) Polymeric prodrug combination to exploit the therapeutic potential of antimicrobial peptides against cancer cells. Org Biomol Chem 14:9278–9286.  https://doi.org/10.1039/C6OB01815G CrossRefPubMedGoogle Scholar
  41. Kirsch SA, Böckmann RA (2016) Membrane pore formation in atomistic and coarse-grained simulations. Biochim Biophys Acta 1858:2266–2277.  https://doi.org/10.1016/j.bbamem.2015.12.031 CrossRefPubMedGoogle Scholar
  42. Kotnik T, Frey W, Sack M, Meglič SH, Peterka M, Miklavčič D (2015) Electroporation-based applications in biotechnology. Trends Biotechnol 33:480–488.  https://doi.org/10.1016/j.tibtech.2015.06.002 CrossRefPubMedGoogle Scholar
  43. Ladokhin AS, Wimley WC, White SH (1995) Leakage of membrane vesicle contents: determination of mechanism using fluorescence requenching. Biophys J 69:1964–1971.  https://doi.org/10.1016/S0006-3495(95)80066-4 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Lee M-T, Chen F-Y, Huang HW (2004) Energetics of pore formation induced by membrane active peptides. Biochemistry 43:3590–3599.  https://doi.org/10.1021/bi036153r CrossRefPubMedGoogle Scholar
  45. Leontiadou H, Mark AE, Marrink SJ (2004) Molecular dynamics simulations of hydrophilic pores in lipid bilayers. Biophys J 86:2156–2164.  https://doi.org/10.1016/S0006-3495(04)74275-7 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Levadny V, Tsuboi T, Belaya M, Yamazaki M (2013) Rate constant of tension-induced pore formation in lipid membranes. Langmuir 29:3848–3852.  https://doi.org/10.1021/la304662p CrossRefPubMedGoogle Scholar
  47. Levine ZA (2017) Lipid electropore lifetime in molecular models. In: Miklavčič D (ed) Handbook of electroporation. Springer, Cham, pp 113–131.  https://doi.org/10.1007/978-3-319-32886-7_86 CrossRefGoogle Scholar
  48. Levine ZA, Vernier PT (2010) Life cycle of an electropore: field-dependent and field-independent steps in pore creation and annihilation. J Membr Biol 236:27–36.  https://doi.org/10.1007/s00232-010-9277-y CrossRefPubMedGoogle Scholar
  49. Litster JD (1975) Stability of lipid bilayers and red blood cell membranes. Phys Lett A 53:193–194.  https://doi.org/10.1016/0375-9601(75)90402-8 CrossRefGoogle Scholar
  50. Lopez J, Tait SWG (2015) Mitochondrial apoptosis: killing cancer using the enemy within. Br J Cancer 112:957–962.  https://doi.org/10.1038/bjc.2015.85 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Mader JS, Hoskin DW (2006) Cationic antimicrobial peptides as novel cytotoxic agents for cancer treatment. Expert Opin Investig Drugs 15:933–946.  https://doi.org/10.1517/13543784.15.8.933 CrossRefPubMedGoogle Scholar
  52. Marrink SJ, Lindahl E, Edholm O, Mark AE (2001) Simulation of the spontaneous aggregation of phospholipids into bilayers. J Am Chem Soc 123:8638–8639.  https://doi.org/10.1021/ja0159618 CrossRefPubMedGoogle Scholar
  53. Marrink SJ, de Vries AH, Tieleman DP (2009) Lipids on the move: simulations of membrane pores, domains, stalks and curves. Biochim Biophys Acta 1788:149–168.  https://doi.org/10.1016/j.bbamem.2008.10.006 CrossRefPubMedGoogle Scholar
  54. Melikov KC, Frolov VA, Shcherbakov A, Samsonov AV, Chizmadzhev YA, Chernomordik LV (2001) Voltage-induced nonconductive pre-pores and metastable single pores in unmodified planar lipid bilayer. Biophys J 80:1829–1836.  https://doi.org/10.1016/s0006-3495(01)76153-x CrossRefPubMedPubMedCentralGoogle Scholar
  55. Miklavčič D (ed) (2017) Handbook of Electroporation. Springer International Publishing, Cham.  https://doi.org/10.1007/978-3-319-32886-7 CrossRefGoogle Scholar
  56. Neale C, Pomès R (2016) Sampling errors in free energy simulations of small molecules in lipid bilayers. Biochim et Biophys Acta 1858:2539–2548.  https://doi.org/10.1016/j.bbamem.2016.03.006 CrossRefGoogle Scholar
  57. Neu JC, Krassowska W (1999) Asymptotic model of electroporation. Phys Rev E 59:3471–3482.  https://doi.org/10.1103/PhysRevE.59.3471 CrossRefGoogle Scholar
  58. Paula S, Volkov AG, Hoek ANV, Haines TH, Deamer DW (1996) Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness. Biophys J 70:339–348.  https://doi.org/10.1016/s0006-3495(96)79575-9 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Portet T, Dimova R (2010) A new method for measuring edge tensions and stability of lipid bilayers: effect of membrane composition. Biophys J 99:3264–3273.  https://doi.org/10.1016/j.bpj.2010.09.032 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Puech P-H, Borghi N, Karatekin E, Brochard-Wyart F (2003) Line thermodynamics: adsorption at a membrane edge. Phys Rev Lett 90:128304CrossRefGoogle Scholar
  61. Raaymakers C, Verbrugghe E, Hernot S, Hellebuyck T, Betti C, Peleman C, Claeys M, Bert W, Caveliers V, Ballet S, Martel A, Pasmans F, Roelants K (2017) Antimicrobial peptides in frog poisons constitute a molecular toxin delivery system against predators. Nat Commun 8:1495.  https://doi.org/10.1038/s41467-017-01710-1 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Rathinakumar, R., Wimley, W.C., 2010. High-throughput discovery of broad-spectrum peptide antibiotics. FASEB J.  https://doi.org/10.1096/fj.10-157040 CrossRefGoogle Scholar
  63. Rems L (2017) Lipid Pores: Molecular and Continuum Models. In: Miklavćić D (ed) Handbook of Electroporation. Springer International Publishing, Cham, pp 3–23.  https://doi.org/10.1007/978-3-319-32886-7_76 CrossRefGoogle Scholar
  64. Robertson J (1960) The molecular structure and contact relationships of cell membranes. Prog Biophys Mol Biol 10:343–418PubMedGoogle Scholar
  65. Sachs JN, Crozier PS, Woolf TB (2004) Atomistic simulations of biologically realistic transmembrane potential gradients. J. Chem. Phys. 121:10847–10851.  https://doi.org/10.1063/1.1826056 CrossRefPubMedGoogle Scholar
  66. Sandre O, Moreaux L, Brochard-Wyart F (1999) Dynamics of transient pores in stretched vesicles. Proc Natl Acad Sci USA 96:10591–10596.  https://doi.org/10.1073/pnas.96.19.10591 CrossRefPubMedGoogle Scholar
  67. Shinoda W (2016) Permeability across lipid membranes. Biochim Biophys Acta 1858:2254–2265.  https://doi.org/10.1016/j.bbamem.2016.03.032 CrossRefPubMedGoogle Scholar
  68. Singer SJ (2004) Some early history of membrane molecular biology. Annu Rev Physiol 66:1–27.  https://doi.org/10.1146/annurev.physiol.66.032902.131835 CrossRefPubMedGoogle Scholar
  69. Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175:720–731CrossRefGoogle Scholar
  70. Tarek M (2005) Membrane Electroporation: a Molecular Dynamics Simulation. Biophys J 88:4045–4053.  https://doi.org/10.1529/biophysj.104.050617 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Taupin C, Dvolaitzky M, Sauterey C (1975) Osmotic pressure-induced pores in phospholipid vesicles. Biochemistry 14:4771–4775CrossRefGoogle Scholar
  72. Tieleman DP (2004) The molecular basis of electroporation. BMC Biochem 5:10.  https://doi.org/10.1186/1471-2091-5-10 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Tieleman DP, Leontiadou H, Mark AE, Marrink S-J (2003) Simulation of pore formation in lipid bilayers by mechanical stress and electric fields. J Am Chem Soc 125:6382–6383.  https://doi.org/10.1021/ja029504i CrossRefPubMedGoogle Scholar
  74. Tokman M, Lee JH, Levine ZA, Ho M-C, Colvin ME, Vernier PT (2013) Electric field-driven water dipoles: nanoscale architecture of electroporation. PLoS ONE 8:e61111.  https://doi.org/10.1371/journal.pone.0061111 CrossRefPubMedPubMedCentralGoogle Scholar
  75. Tolpekina TV, den Otter WK, Briels WJ (2004) Nucleation free energy of pore formation in an amphiphilic bilayer studied by molecular dynamics simulations. J Chem Phys 121:12060–12066.  https://doi.org/10.1063/1.1815296 CrossRefPubMedGoogle Scholar
  76. Tsong TY (1991) Electroporation of cell membranes. Biophys J 60:297–306.  https://doi.org/10.1016/s0006-3495(91)82054-9 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Unsay JD, Cosentino K, Sporbeck K, García-Sáez AJ (2017) Pro-apoptotic cBid and Bax exhibit distinct membrane remodeling activities: an AFM study. Biochim Biophys Acta 1859:17–27.  https://doi.org/10.1016/j.bbamem.2016.10.007 CrossRefGoogle Scholar
  78. Vernier PT, Ziegler MJ (2007) Nanosecond field alignment of head group and water dipoles in electroporating phospholipid bilayers. J. Phys. Chem. B 111:12993–12996.  https://doi.org/10.1021/jp077148q CrossRefPubMedGoogle Scholar
  79. Wang Y, Zhao T, Wei D, Strandberg E, Ulrich AS, Ulmschneider JP (2014) How reliable are molecular dynamics simulations of membrane active antimicrobial peptides? Biochim Biophys Acta 1838:2280–2288.  https://doi.org/10.1016/j.bbamem.2014.04.009 CrossRefPubMedGoogle Scholar
  80. Wang G, Li X, Wang Z (2015) APD3: the antimicrobial peptide database as a tool for research and education. Nucleic Acids Res 44:D1087–D1093.  https://doi.org/10.1093/nar/gkv1278 CrossRefPubMedPubMedCentralGoogle Scholar
  81. Weaver JC, Chizmadzhev YA (1996) Theory of electroporation: a review. Bioelectrochem Bioenerg 41:135–160.  https://doi.org/10.1016/s0302-4598(96)05062-3 CrossRefGoogle Scholar
  82. Wohlert J, den Otter WK, Edholm O, Briels WJ (2006) Free energy of a trans-membrane pore calculated from atomistic molecular dynamics simulations. J Chem Phys 124:154905.  https://doi.org/10.1063/1.2171965 CrossRefPubMedGoogle Scholar
  83. Zhelev DV, Needham D (1993) Tension-stabilized pores in giant vesicles: determination of pore size and pore line tension. Biochim Biophys Acta 1147:89–104.  https://doi.org/10.1016/0005-2736(93)90319-u CrossRefPubMedGoogle Scholar
  84. Ziegler MJ, Vernier PT (2008) Interface water dynamics and porating electric fields for phospholipid bilayers. J. Phys. Chem. B 112:13588–13596.  https://doi.org/10.1021/jp8027726 CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Institute of Molecular Science (ICMol), Universitat de ValènciaPaternaSpain

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