Advertisement

European Biophysics Journal

, 36:973 | Cite as

Membrane perturbation by an external electric field: a mechanism to permit molecular uptake

  • J.-M. Escoffre
  • D. S. Dean
  • M. Hubert
  • M.-P. Rols
  • C. Favard
Review
First Online:
Received:
Revised:
Accepted:

Abstract

Electropermeabilisation is a well established physical method, based on the application of electric pulses, which induces the transient permeabilisation of the cell membrane. External molecules, otherwise nonpermeant, can enter the cell. Electropermeabilisation is now in use for the delivery of a large variety of molecules, as drugs and nucleic acids. Therefore, the method has great potential in the fields of cancer treatment and gene therapy. However many open questions about the underlying physical mechanisms involved remain to be answered or fully elucidated. In particular, the induced changes by the effects of the applied field on the membrane structure are still far from being fully understood. The present review focuses on questions related to the current theories, i.e. the basic physical processes responsible for the electropermeabilisation of lipid membranes. It also addresses recent findings using molecular dynamics simulations as well as experimental studies of the effect of the field on membrane components.

Keywords

Molecular Dynamic Simulation External Electric Field Pore Formation Pulse Electric Field Potential Drop 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

PC

Phosphatidyl-Choline

PS

Phosphatidyl-Serine

PE

Phosphatidyl-Ethanolamine

SM

Sphingomyelin

DOPC

1,2-Dioleoyl-sn-Glycero-3-Phosphocholine

DOPS

1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine

NBD

7-Nitrobenz-2-oxa-1,3-diazol-4-yl

This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was supported by the Association Française contre les Myopathies.

References

  1. Abidor IG, Arakelyan VB, Chernomordik LV, Chizmadzhev YA, Pastushenko VF, Tarasevich (1979) Electric breakdown of bilayer membranes I: the main experimental facts and their qualitative description. Bioelectrochem Bioenerg 6:37–52CrossRefGoogle Scholar
  2. Antov Y, Barbul A, Mantsur H, Korenstein R (2005) Electroendocytosis: exposure of cells to pulsed low electric fields enhances adsorption and uptake of macromolecules. Biophys J 88:2206–2223CrossRefGoogle Scholar
  3. Barnett A, Weaver JC (1991) Electroporation: a unified, quantitative theory of reversible electrical breakdown and mechanical rupture in artificial planar bilayer membranes. Biolectrochem Bioenerg 25:163–182CrossRefGoogle Scholar
  4. Beebe SJ, Schoenbach KH (2005) Nanosecond pulsed electric fields: a new stimulus to activate intracellular signalling. J Biomed Biotechnol 4:297–300CrossRefGoogle Scholar
  5. Beebe SJ, White J, Blackmore PF, Deng Y, Somers K and Schoenbach KH (2003) Diverse effects of nanosecond pulsed electric fields on cells and tissues. DNA Cell Biol 22:785–796CrossRefGoogle Scholar
  6. Belehradek M, Domenge C, Luboinski B, Orlowski S, Belehradek J Jr, Mir LM (1993) Electrochemotherapy, a new antitumor treatment. First Clin Phase I-II Trial Cancer 72:3694–700Google Scholar
  7. Bernhardt J, Pauly H (1973) On the generation of potential difference across the membrane of ellipsoidal cells in an alternating electric field. Biophysik 10:89–98CrossRefGoogle Scholar
  8. Bigey P, Bureau MF, Scherman D (2002) In vivo plasmid DNA electrotransfer. Curr Opin Biotechnol 13:443–447CrossRefGoogle Scholar
  9. Cartee LA, Plonsey R (1992) The transient subthreshold response of spherical and cylindrical cell models to extracellular stimulation. IEEE Trans Biomed Eng 39:76–85CrossRefGoogle Scholar
  10. Chen W (2005) Electroconformational denaturation of membrane proteins. Ann N Y Acad Sci 1066:92–105CrossRefADSGoogle Scholar
  11. Chen W, Lee RC (1994) Altered ion channel conductance and ionic selectivity induced by large imposed membrane potential pulse. Biophys J 67:603–612Google Scholar
  12. Crowley JM (1973) Electrical breakdown of bimolecular lipid membranes as an electromechanical instability. Biophys J 13:711–24Google Scholar
  13. Derjaguin BV, Gutop YV (1961) Theory of the breakdown (rupture) of free films. Kolloidn Zh 24:370–374Google Scholar
  14. Devaux PF (2000) Is lipid translocation involved during endo-exocytosis? Biochimie 82:497–509CrossRefGoogle Scholar
  15. Dressler V, Schwister K, Haest CW, Deuticke B (1983) Dielectric breakdown of the erythrocyte membrane enhances transbilayer mobility of phospholipids. Biochim Biophys Acta 732:304–307CrossRefGoogle Scholar
  16. Favard C, Dean DS, Rols MP (2007) Electrotransfer as a non viral method of gene delivery. Curr Gene Ther 7:67–77CrossRefGoogle Scholar
  17. Gabriel B, Teissie J (1997) Direct observation in the millisecond time range of fluorescent molecule asymmetrical interaction with the electropermeabilized cell membrane. Biophys J 73:2630–2637Google Scholar
  18. Gehl J, Sorensen TH, Nielsen K, Raskmark P, Nielsen SL, Skovsgaard T, Mir LM (1999) In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochim Biophys Acta 1428:233–240Google Scholar
  19. Gilbert RA, Jaroszeski MJ, Heller R (1997) Novel electrode designs for electrochemotherapy. Biochim Biophys Acta 1334:9–14Google Scholar
  20. Glaser RW, Leikin SL, Chernomordik LV, Pastushenko VF, Sokirko AI (1988) Reversible electrical breakdown of lipid bilayers and formation and evolution of pores. Biochem Biophys Acta 940:275–287CrossRefGoogle Scholar
  21. Golzio M, Teissie J, Rols MP (2002) Direct visualization at the single-cell level of electrically mediated gene delivery. Proc Natl Acad Sci U S A 99:1292–1297CrossRefADSGoogle Scholar
  22. Gowrishankar TR, Esser AT, Vasilkoski Z, Smith KC, Weaver JC (2006) Microdosimetry for conventional and supra-electroporation in cells with organelles. Biochem Biophys Res Comm 341:1266–1276CrossRefGoogle Scholar
  23. Haest CWM, Kamp D, Deuticke B (1997) Transbilayer reorientation of phospholipids probes in the human erythrocytes membrane. Lessons from studies on electroporated and resealed cells. Biochim Biophys Acta 1325:17–33CrossRefGoogle Scholar
  24. Hibino M, Itoh H, Kinosita K, (1993) Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. Biophys J 64:1789–1800Google Scholar
  25. Hol WGJ (1985) Effects of the alpha-helix dipole upon the functioning and structure of proteins and peptides. Adv Biophys 19:133–165CrossRefGoogle Scholar
  26. Isambert H (1998) Understanding the electroporation of cells and artificial bilayer membranes. Phys Rev Lett 80:3404–3407CrossRefADSGoogle Scholar
  27. Janmey PA and Kinnunen PKJ (2006) Biophysical properties of lipids and dynamics membranes. Trends Cell Biol 16:538–546CrossRefGoogle Scholar
  28. Karateki 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 84:1734–1749Google Scholar
  29. Kolb JF, Kono S, Schoenbach KH (2006) Nanosecond pulsed electric field generators for the study of subcellular effects. Bioelectromagnetics 27:172–187CrossRefGoogle Scholar
  30. Kotnik T, Miklavcic D (2000) Analytical description of transmembrane voltage induced by electric field on spheroidal cells. Biophys J 79:670–679Google Scholar
  31. Kotulska M, Kubica K, Koronkiewicz S, Kalinowski S (2007) Modeling of the induction of lipid membrane electropermeabilization. Bioelectrochemistry 70:64–70CrossRefGoogle Scholar
  32. Krassowka W, Filev PD (2007) Modeling electroporation in a single cell. Biophys J 92:404–417CrossRefGoogle Scholar
  33. Landau LD, Lifshitz EM (1975) Electrodynamics of continuous media. Pergamon Press, OxfordGoogle Scholar
  34. Leontiadou H, Mark AE, Marrink SJ (2004) Molecular dynamics simulations of hydrophilic pores in lipid bilayers. Biophys J 86:2156–2164CrossRefGoogle Scholar
  35. Lin-Liu R, Adey WR, Poo MM (1984) Migration of cell surface concanavalin A receptors in pulsed electric fields. Biophys J 45:1211–1217Google Scholar
  36. Mahrour N, Pologea-Moraru R, Moisescu MG, Orlowski S, Levêque P, Mir LM (2005) In vitro increase of the fluid-phase endocytosis induced by pulsed radiofrequency electromagnetic fields: importance of the electric field component. Biochem Biophys Acta 1668:126–137CrossRefGoogle Scholar
  37. McLaughlin S, Poo MM (1981) The role of electro-osmosis in the electric-field-induced movement of charged macromolecules on the surfaces of cells. Biophys J 34:85–93Google Scholar
  38. Miklavcic D, Semrov D, Mekid H, Mir LM (2000) A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. Biochim Biophys Acta 1523:73–83Google Scholar
  39. Mir LM, Belehradek M, Domenge C, Orlowski S, Poddevin B, Belehradek J Jr, Schwaab G, Luboinski B, Paoletti C (1991a) Electrochemotherapy, a new antitumor treatment: first clinical trial. C R Acad Sci III 313:613–618Google Scholar
  40. Mir LM, Orlowski S, Belehradek J Jr, Paoletti C (1991b) Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur J Cancer 27:68–72CrossRefGoogle Scholar
  41. Neu JC, Krassowska W (2003) Modeling postshock evolution of large electropores. Phys Rev E 67:021915–021926CrossRefADSGoogle Scholar
  42. Neu JC, Smith KC, Krassowska W (2003) Electrical energy required to form large conducting pores. Bioelectrochem Bioenerg 60:107–114Google Scholar
  43. Neumann E, Rosenheck K (1972) Permeability changes induced by electric impulses in vesicular membranes. J Membr Biol 10:279–290CrossRefGoogle Scholar
  44. Neumann E, Sowers AE, Jordan CA (1989), Electroporation and electrofusion in cell biology. Plenum, New YorkGoogle Scholar
  45. Pastushenko VF, Chizmadzhev YA, Arekelyan VB (1979) Electric breakdown of bilayer membranes II. Calculation of the membrane lifetime in the steady-state diffusion approximation. Bioelectrochem Bioenerg 6:53–62Google Scholar
  46. Pavlin M, Pavselj, Miklavcic D (2002) Dependence of induced transmembrane potential on cll density, arrangement, and cell position inside a cell system. IEEE Trans Biomed Eng 49:605–612CrossRefGoogle Scholar
  47. Powell KT, Weaver JC (1986) Transient aqueous pores in bilayer membranes: a statistical theory. Bioelectrochem Bioenerg 15:211–227CrossRefGoogle Scholar
  48. Rols MP (2006) Electropermeabilization, a physical method for the delivery of therapeutic molecules into cells. Biochim Biophys Acta 1758:423–428CrossRefGoogle Scholar
  49. Sale AJ, Hamilton WA (1968) Effects of high electric fields on micro-organisms. 3. Lysis of erythrocytes and protoplasts. Biochim Biophys Acta 163:37–43CrossRefGoogle Scholar
  50. Sandre O, Moreaux L, Brochard-Wyart F (1999) Dynamics of transient pores in stretched membranes. Proc Nat Acad Sci USA 96:10591–10596CrossRefADSGoogle Scholar
  51. Schwan HP (1957) Electrical properties of tissue and cell suspensions. Adv Biol Med Phys 5:147–209Google Scholar
  52. Sens P, Isambert H (2002) Undulation instability of lipid membranes under an electric field. Phys Rev Lett 88:128102–128105CrossRefADSGoogle Scholar
  53. Smith KC, Neu JC, Krassowska W (2004) Model of creation and evolution of stable electropores for DNA delivery. Biophys J 86:2813–2826Google Scholar
  54. Sukharev SI, Klenchin VA, Serov SM, Chernomordik LV, Chizmadzhev Yu A (1992) Electroporation and electrophoretic DNA transfer into cells. The effect of DNA interaction with electropores. Biophys J 63:1320–1327Google Scholar
  55. Susil R, Semerov D, Miklavcic (1998) Electric field-induced transmembrane potential depends on cell density and organization. Electro-Magnetobiol 17:391–399Google Scholar
  56. Tarek M (2005) Membrane electroporation: a molecular dynamics simulation. Biophys J 88:4015–4053CrossRefGoogle Scholar
  57. Teissie J, Rols MP (1993) An experimental evaluation of the critical potential difference inducing cell membrane electropermeabilization. Biophys J 65:409–413Google Scholar
  58. Teissie J, Tsong TY (1980) Evidence of voltage-induced channel opening in Na/K ATPase of human erythrocyte membrane. J Membr Biol 55:133–140CrossRefGoogle Scholar
  59. Teissie J, Eynard N, Vernhes MC, Benichou A, Ganeva V, Galutzov B, Cabanes PA (2002) Recent biotechnological developments of electropulsation. A prospective review. Bioelectrochemistry 55:107–112CrossRefGoogle Scholar
  60. Teissie J, Golzio M, Rols MP (2005) Mechanisms of cell membrane electropermeabilization: a minireview of our present (lack of ?) knowledge. Biochim Biophys Acta 1724:270–280Google Scholar
  61. Tekle E, Oubrahim H, Dzekunov SM, Kolb JF, Schoenbach KH, Chock PB (2005) Selective field effects on intracellular vacuoles and vesicle membranes with nanosecond electric pulses. Biophys J 89:274–284CrossRefGoogle Scholar
  62. Tieleman DP (2004) The molecular basis of electroporation. BMC Biochem 5:10CrossRefGoogle Scholar
  63. Tieleman DP (2006) Computer simulations of transport through membranes:passive diffusion, pores, channels and transporters. Clin Exp Pharm Phys 33:893–903CrossRefGoogle Scholar
  64. Tsuji K, Neumann E (1983) Conformational flexibility of membrane proteins in electric fields I. Ultraviolet absorbance and light scattering of bacteriorhodopsin in purple membranes. Biophys Chem 17:153–163CrossRefGoogle Scholar
  65. Vernier PT, Sun Y, Marcu L, Craft CM, Gundersen MA (2004) Nanoelectropulse-induced phosphatidylserine translocation. Biophys J 86:4040–4048CrossRefGoogle Scholar
  66. Vernier PT, Ziegler MJ, Sun Y, Gundersen MA, Tieleman DP (2006a) Nanopore-facilitated, voltage-driven phosphatidylserine translocation in lipid bilayers-in cells and in silico. Phys Biol 3:233–247CrossRefADSGoogle Scholar
  67. Vernier PT, Sun Y, Gundersen MA (2006b) Nanoelectropulse-driven membrane perturbation and small molecule permeabilization. BMC Cell Biol 7:1–16CrossRefGoogle Scholar
  68. Weaver JC (1995) Electroporation theory. Concepts and mechanisms. Methods Mol Biol 55:3–28Google Scholar
  69. Wilhelm C, Winterhalter M, Zimmermann U, Benz R (1993) Kinetics of pore size during irreversible electric breakdown of lipid bilayer membranes. Biophys J 64:121–128Google Scholar
  70. Winterhalter M, Helfrich W (1987) Effect of voltage on pores in membranes. Phys Rev A 36:5874–5876CrossRefADSGoogle Scholar
  71. Wohlert J, den Otter WK, Edholm O, Briels WJ (2006) Free energy of a trans-membrane pore calculated from atomist molecular dynamics simulations. J Chem Phys 124:154905–154914CrossRefADSGoogle Scholar
  72. Yurong Q, Shengli L, Yuehua J, Taicheng Y, Jie W (2005) Transmembrane voltage induced on a cell membrane in suspensions exposed to an alternating field: a theoretical analysis. Bioelectrochemistry 67:57–65CrossRefGoogle Scholar
  73. Zhao M, Dick A, Forrester JV and McCaig CD (1999) Electric field-directed cell motility involves up-regulated expression and asymmetric redistribution of the epidermal growth factor receptors and is enhanced by fibronectin and laminin. Mol Biol 10:1259–1276Google Scholar
  74. Zhelev DV, Needham D (1993) Tension stablized pores in giant vesciles: determination of pore size and pore line tensions. Biophys Acta 1147:89–104CrossRefGoogle Scholar
  75. Zimmermann U, Pilwat G, Riemann F (1974) Dielectric breakdown of cell membranes. Biophys J 14:881–899Google Scholar

Copyright information

© EBSA 2007

Authors and Affiliations

  1. 1.Institut de Pharmacologie et de Biologie Structurale - CNRS UMR 5089Toulouse Cedex 4France
  2. 2.Laboratoire de Physique Théorique - CNRS UMR 5152, IRSAMCUniversité Paul SabatierToulouse Cedex 4France
  3. 3.Institut Fresnel - CNRS UMR 6133Marseille Cedex 20France

Personalised recommendations

Cite article

Buy options