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On the Electroporation Thresholds of Lipid Bilayers: Molecular Dynamics Simulation Investigations

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Abstract

Electroporation relates to the cascade of events that follows the application of high electric fields and that leads to cell membrane permeabilization. Despite a wide range of applications, little is known about the electroporation threshold, which varies with membrane lipid composition. Here, using molecular dynamics simulations, we studied the response of dipalmitoyl-phosphatidylcholine, diphytanoyl-phosphocholine-ester and diphytanoyl-phosphocholine-ether lipid bilayers to an applied electric field. Comparing between lipids with acyl chains and methyl branched chains and between lipids with ether and ester linkages, which change drastically the membrane dipole potential, we found that in both cases the electroporation threshold differed substantially. We show, for the first time, that the electroporation threshold of a lipid bilayer depends not only on the “electrical” properties of the membrane, i.e., its dipole potential, but also on the properties of its component hydrophobic tails.

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References

  • Antonov VF, Smirnova EY, Shevchenko EV (1990) Electric field increases the phase transition temperature in the bilayer membrane of phosphatidic acid. Chem Phys Lipids 52:251–257

    Article  CAS  PubMed  Google Scholar 

  • Benvegnu T, Brard M, Plusquellec D (2004) Archaeabacteria bipolar lipid analogues: structure, synthesis and lyotropic properties. Curr Opin Colloid Interface Sci 8:469–479

    Article  CAS  Google Scholar 

  • Breton M, Delemotte L, Silve A, Mir LM, Tarek M (2012) Nanosecond pulsed electric field driven transport of siRNA molecules through lipid membranes: an experimental and computational study. J Am Chem Soc 134:13938–13941

    Article  CAS  PubMed  Google Scholar 

  • Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N·log(N) method for Ewald sums in large systems. J Chem Phys 98:10089

    Article  CAS  Google Scholar 

  • Daud AI, DeConti RC, Andrews S et al (2008) Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 26:5896–5903

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Davalos RV, Mir LM, Rubinsky B (2005) Tissue ablation with irreversible electroporation. Ann Biomed Eng 33:223–231

    Article  CAS  PubMed  Google Scholar 

  • Delemotte L, Tarek M (2012) Molecular dynamics simulations of lipid membrane electroporation. J Membr Biol 245:531–543

    Article  CAS  PubMed  Google Scholar 

  • Delemotte L, Dehez F, Treptow W, Tarek M (2008) Modeling membranes under a transmembrane potential. J Phys Chem B 112:5547–5550

    Article  CAS  PubMed  Google Scholar 

  • Denet A-R, Vanbever R, Préat V (2004) Skin electroporation for transdermal and topical delivery. Adv Drug Deliv Rev 56:659–674

    Article  CAS  PubMed  Google Scholar 

  • Elbayoumi TA, Torchilin VP (2010) Current trends in liposome research. Methods Mol Biol 605:1–27

    Article  CAS  PubMed  Google Scholar 

  • Essmann U, Perera L, Berkowitz ML et al (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577

    Article  CAS  Google Scholar 

  • Fernández ML, Marshall G, Sagués F, Reigada R (2010) Structural and kinetic molecular dynamics study of electroporation in cholesterol-containing bilayers. J Phys Chem B 114:6855–6865

    Article  PubMed  Google Scholar 

  • Gawrisch K, Ruston D, Zimmerberg J et al (1992) Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. Biophys J 61:1213–1223

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Haberl S, Miklavcic D, Sersa G et al (2013) Cell membrane electroporation—part 2. The applications. IEEE Electr Insulation Mag 29:29–37

    Article  Google Scholar 

  • Hanford MJ, Peeples TL (2002) Archaeal tetraether lipids: unique structures and applications. Appl Biochem Biotechnol 97:45–62

    Article  CAS  PubMed  Google Scholar 

  • Kalé L, Skeel R, Bhandarkar M et al (1999) NAMD2: greater scalability for parallel molecular dynamics. J Comput Phys 151:283–312

    Article  Google Scholar 

  • Klauda JB, Venable RM, Freites JA et al (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 Central  CAS  PubMed  Google Scholar 

  • Kramar P, Delemotte L, Lebar AM et al (2012) Molecular-level characterization of lipid membrane electroporation using linearly rising current. J Membr Biol 245:651–659

    Article  CAS  PubMed  Google Scholar 

  • Kucerka N, Nagle JF, Sachs JN et al (2008) Lipid bilayer structure determined by the simultaneous analysis of neutron and X-ray scattering data. Biophys J 95:2356–2367

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Lindahl E, Edholm O (2000) Spatial and energetic–entropic decomposition of surface tension in lipid bilayers from molecular dynamics simulations. J Chem Phys 113:3882

    Article  CAS  Google Scholar 

  • Napotnik TB, Rebersek M, Kotnik T et al (2010) Electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells. Med Biol Eng Comput 48:407–413

    Article  PubMed Central  PubMed  Google Scholar 

  • Needham D, Hochmuth RM (1989) Electro-mechanical permeabilization of lipid vesicles. Role of membrane tension and compressibility. Biophys J 55:1001–1009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Neumann E, Rosenheck K (1972) Permeability changes induced by electric impulses in vesicular membranes. J Membr Biol 10:279–290

    Article  CAS  PubMed  Google Scholar 

  • Peterson U, Mannock DA, Lewis RNA et al (2002) Origin of membrane dipole potential: contribution of the phospholipid fatty acid chains. Chem Phys Lipids 117:19–27

    Article  CAS  PubMed  Google Scholar 

  • Portet T, Camps I, Febrer F, Escoffre J-M et al (2009) Visualization of membrane loss during the shrinkage of giant vesicles under electropulsation. Biophys J 96:4109–4121

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ridi A, Scalas E, Robello M, Gliozzi A (1998) Linear response of a fluctuating lipid bilayer. Thin Solid Films 327–329:796–799

    Article  Google Scholar 

  • Sachs JN, Crozier PS, Woolf TB (2004) Atomistic simulations of biologically realistic transmembrane potential gradients. J Chem Phys 121:10847–10851

    Article  CAS  PubMed  Google Scholar 

  • Sersa G, Miklavcic D, Cemazar M et al (2008) Electrochemotherapy in treatment of tumours. Eur J Surg Oncol 34:232–240

    Article  CAS  PubMed  Google Scholar 

  • Shinoda W, Mikami M, Baba T, Hato M (2003) Molecular dynamics study on the effect of chain branching on the physical properties of lipid bilayers: structural stability. J Phys Chem B 107:14030–14035

    Article  CAS  Google Scholar 

  • Shinoda K, Shinoda W, Baba T, Mikami M (2004a) Comparative molecular dynamics study of ether- and ester-linked phospholipid bilayers. J Chem Phys 121:9648–9654

    Article  CAS  PubMed  Google Scholar 

  • Shinoda W, Mikami M, Baba T, Hato M (2004b) Molecular dynamics study on the effects of chain branching on the physical properties of lipid bilayers: 2. Permeability. J Phys Chem B 108:9346–9356

    Article  CAS  Google Scholar 

  • Tarek M (2005) Membrane electroporation: a molecular dynamics simulation. Biophys J 88:4045–4053

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tieleman DP (2004) The molecular basis of electroporation. BMC Biochem 5:10

    Article  PubMed Central  PubMed  Google Scholar 

  • Tockman 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(4):e61111

    Article  Google Scholar 

  • Toepfl S, Heinz V, Knorr D (2007) High intensity pulsed electric fields applied for food preservation. Chem Eng Process 46:537–546

    Article  CAS  Google Scholar 

  • Ulrih NP, Gmajner D, Raspor P (2009) Structural and physicochemical properties of polar lipids from thermophilic Archaea. Appl Microbiol Biotechnol 84:249–260

    Article  CAS  PubMed  Google Scholar 

  • Vernhes M, Benichou A, Pernin P et al (2002) Elimination of free-living amoebae in fresh water with pulsed electric fields. Water Res 36:3429–3438

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Bose PS, Sigworth FJ (2006) Using cryo-EM to measure the dipole potential of a lipid membrane. Proc Natl Acad Sci USA 103:18528–18533

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu Y, He K, Ludtke SJ, Huang HW (1995) X-ray diffraction study of lipid bilayer membranes interacting with amphiphilic helical peptides: diphytanoyl phosphatidylcholine with alamethicin at low concentrations. Biophys J 68:2361–2369

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ziegler MJ, Vernier PT (2008) Interface water dynamics and porating electric fields for phospholipid bilayers. J Phys Chem B 112:13588–13596

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was in part supported by the Slovenian Research Agency. Research was conducted in the scope of the EBAM European Associated Laboratory. The article is a result of the networking efforts of COST Action TD1104. Part of the calculations and the finalization of the article was performed during the Short-Term Scientific Mission (Grant 070113-021794, to A. P.). Simulations were performed using HPC resources from GENCI-CINES (Grant 2012-076434). The authors thank the ANR Intcell program (ANR-10-BLAN-096).

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Correspondence to Mounir Tarek.

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Polak, A., Bonhenry, D., Dehez, F. et al. On the Electroporation Thresholds of Lipid Bilayers: Molecular Dynamics Simulation Investigations. J Membrane Biol 246, 843–850 (2013). https://doi.org/10.1007/s00232-013-9570-7

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  • DOI: https://doi.org/10.1007/s00232-013-9570-7

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