Membrane electroporation theories: a review

  • C. Chen
  • S.W. SmyeEmail author
  • M.P. Robinson
  • J.A. Evans


Electroporation, the transient increase in the permeability of cell membranes when exposed to a high electric field, is an established in vitro technique and is used to introduce DNA or other molecules into cells. When the trans-membrane voltage induced by an external electric field exceeds a certain threshold (normally 0.2–1 V), a rearrangement of the molecular structure of the membrane occurs, leading to pore formation in the membrane and a considerable increase in the cell membrane permeability to ions, molecules and even macromolecules. This phenomenon is, potentially, the basis for many in vivo applications such as electrochemotherapy and gene therapy, but still lacks a comprehensive theoretical basis. This article reviews the state of current electroporation theories and briefly considers current and potential applications in biology and medicine.


Electroporation Electropermeabilisation Cell membrane Aqueous pore model Electric fields 


  1. 1.
    Abidor IG, Arakelyan VB, Chernomordik LV, Chizmadzhev YA, Pastushenko VF, Tarasevich MR (1979) Electric breakdown of bilayer membranes: 1. The main experimental facts and their qualitative discussion. Bioelectrochem Bioenerg 6:37–52CrossRefGoogle Scholar
  2. 2.
    Aksimentiev A, Jiunn BH, Timp G, Schulten K (2004) Microscopic kinetics of DNA translocation through synthetic nanopores. Biophys J 87:2086–2097CrossRefPubMedGoogle Scholar
  3. 3.
    Alberts B, Bray D, Johnson A, Lewis J, Raff M, Roberts K, Walter P (1998) Essential cell biology. Garland Publishing, New York, NYGoogle Scholar
  4. 4.
    Al-Khadra A, Nikolski V, Efimov IR (2001) The role of electroporation in defibrillation. Circ Res 87:797–804Google Scholar
  5. 5.
    Alvarez O, Latorre RE (1978) Voltage dependent capacitance in lipid bilayers made from monolayers. Biophys J 21:1–17PubMedGoogle Scholar
  6. 6.
    Ashihara T, Yao T, Namba T, Makoto I, Ikeda T, Kawase A, Toda S, Suzuki T, Inagaki M, Sugimachi M, Kinoshita M, Nakazawa K (2001) Electroporation in a model of defibrillation. J Cardiovasc Res 12:1393–1403Google Scholar
  7. 7.
    Baker PF, Knight DE (1978) A high-voltage technique for gaining rapid access to the interior of secretory cells. J Physiol 284:30–31Google Scholar
  8. 8.
    Baker PF, Knight DE (1979) Influence of anions on exocytosis in ‘leaky’ bovine adrenal medullary cells. J Physiol 296:106–107Google Scholar
  9. 9.
    Barnett A, Weaver JC (1991) Electroporation: a unified, quantitative theory of reversible breakdown and rupture. Biolectrochem Bioenerg 25:163–182CrossRefGoogle Scholar
  10. 10.
    Benz R, Beckers F, Zimmerman U (1979) Reversible electrical breakdown of lipid bilayer membranes: a charge pulse relaxation study. J Membr Biol 48:181–204PubMedCrossRefGoogle Scholar
  11. 11.
    Chang DC (1992) Structure and dynamics of electric field-induced membrane pores as revealed by rapid-freezing electron microscopy. Guide to electroporation and electrofusion. Academic, Orlando, FL, pp 9–27Google Scholar
  12. 12.
    Crowley JM (1973) Electrical breakdown of bimolecular lipid membranes as an electromechanical instability. Biophys J 13:711–724PubMedGoogle Scholar
  13. 13.
    DeBruin KA, Krassowska W (1999) Modeling electroporation in a single cell. I. Effects of field strength and rest potential. Biophys J 77:1213–1224PubMedGoogle Scholar
  14. 14.
    Dimitrov DS (1984) Electric field-induced breakdown of lipid bilayers and cell membranes: a thin viscoelastic film model. J Membr Biol 78:53–60CrossRefPubMedGoogle Scholar
  15. 15.
    Engstrom PE, Persson BR, Salford LG (1999) Studies of in vivo electropermeabilisation by gamma camera measurements of (99m)Tc-DTPA. Biochim Biophys Acta 1428:321–328Google Scholar
  16. 16.
    Freeman SA, Wang MA, Weaver JC (1994) Theory of electroporation of planar bilayer membranes: predictions of the aqueous area, change in capacitance, and pore–pore separation. Biophys J 67:42–56PubMedGoogle Scholar
  17. 17.
    Gauger B, Bentrup FW (1979) A study of dielectric membrane breakdown in the Fucus egg. J Membr Biol 48(3):249–264PubMedCrossRefGoogle Scholar
  18. 18.
    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 940:275–287PubMedCrossRefGoogle Scholar
  19. 19.
    Gothelf A, Mir LM, Gehl J (2003) Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat Rev 29:371–387PubMedCrossRefGoogle Scholar
  20. 20.
    Grosse C, Schwan HP (1992) Cellular membrane potentials induced by alternating fields. Biophys J 63:1632–1642Google Scholar
  21. 21.
    Hoekstra D (1994) Cell lipids, current topics in membranes, vol 40. Academic Press, New York, NY, International Standard Serial Number: 0070-2161Google Scholar
  22. 22.
    Israelachvili JN, Marcelja S, Horn RG (1980) Physical principles of membrane organization. Q Rev Biophys 13:121–200PubMedCrossRefGoogle Scholar
  23. 23.
    Jaroszeski MJ, Gilbert R, Heller R (2000) Electrically mediated delivery of molecules to cells: electrochemotherapy, electrogenetherapy and transdermal delivery by electroporation. Humana Press, Totowa, NJGoogle Scholar
  24. 24.
    Joshi RP, Schoenbach KH (2000) Electroporation dynamics in biological cells subjected to ultrafast electrical pulses. Phys Rev E 62:1025–1033CrossRefGoogle Scholar
  25. 25.
    Joshi RP, Hu Q, Aly R, Schoenbach KH, Hjalmarson HP (2001) Self-consistent simulations of electroporation dynamics in biological cells subjected to ultrashort pulses. Phys Rev E 64:011913-1–011913-10CrossRefGoogle Scholar
  26. 26.
    Joshi RP, Hu Q, Schoenbach KH, Hjalmarson HP (2002) Improved energy model for membrane electroporation in biological cells subjected to electrical pulses. Phys Rev E 65:041920-1–041920-8Google Scholar
  27. 27.
    Kinosita K, Tsong TY (1977) Formation and resealing of pores of controlled sizes in human erythrocyte membranes. Nature 268:438–443CrossRefPubMedGoogle Scholar
  28. 28.
    Klenchin VA, Sukharev SI, Serov SM, Chernomordik LV, Chizmadzhev YA (1991) Electrically induced DNA uptake by cells is a fast process involving DNA electrophoresis. Biophys J 60:804–811PubMedGoogle Scholar
  29. 29.
    Kotnik T, Mir LM, Flisar K, Puc M, Miklav ID (2001) Cell membrane electropermeabilization by symmetrical bipolar rectangular pulses: part I. Increased efficiency of permeabilization. Bioelectrochemistry 54:83–89CrossRefPubMedGoogle Scholar
  30. 30.
    Krakowsky I, Romijn T, Posthuman ADB (1989) A few remarks on the electrostriction of elastomers. J Appl Phys 85:628–629CrossRefGoogle Scholar
  31. 31.
    Krassowska W (1995) Effects of electroporation on transmembrane potential induced by defibrillation shocks. Pacing Clin Electrophysiol 18:1644–1660PubMedCrossRefGoogle Scholar
  32. 32.
    Lewis TJ (2003) A model for bilayer membrane electroporation based on resultant electromechanical stress. IEEE Trans Dielectr Electr Insul 10:754–768CrossRefGoogle Scholar
  33. 33.
    Litster JD (1975) Stability of lipid bilayers and red blood cell membranes. Phys Lett 53A:193–194Google Scholar
  34. 34.
    Maldarelli C, Jain R, Ruckstein E (1980) J Colloid Interface Sci 72:118–125CrossRefGoogle Scholar
  35. 35.
    Michael DH, O’Neil ME (1970) Electrohydrodynamic instability in plane layers of fluid. J Fluid Mech 41:571–580zbMATHCrossRefGoogle Scholar
  36. 36.
    Miklavcic D, Beravs K, Semrov D, Cemazar M, Demsar F, Sersa G (1998) The importance of electric field distribution for effective in vivo electroporation of tissues. Biophys J 74:2152–2158PubMedGoogle Scholar
  37. 37.
    Miller IR (1981) Structural and energetic aspects of charge transport in lipid bilayers and biological membranes. In: Milazzo G (eds) Topics in bioelectrochemistry and bioenergetics, vol 4. Wiley, New York, NY, pp 161–224Google Scholar
  38. 38.
    Mir LM (2000) Therapeutic perspectives of in vivo cell electropermeabislisation. Bioelectrochemistry 53:1–10CrossRefGoogle Scholar
  39. 39.
    Montal M, Mueller P (1972) Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proc Natl Acad Sci USA 69:3561–3566PubMedCrossRefGoogle Scholar
  40. 40.
    Neu JC, Krassowski W (1999) Asymptotic model of electroporation. Phys Rev E 59:3471–3482CrossRefGoogle Scholar
  41. 41.
    Neumann E, Rosenheck K (1972) Permeability changes induced by electric impulses in vesicular membranes. J Membr Biol 10:279–290CrossRefPubMedGoogle Scholar
  42. 42.
    Neumann E, Sprafke A, Boldt E, Wolf H (1992) Biophysical digression on membrane electroporation. In: Chang DC, Chassy BM, Saunders JA, Sowers AE (eds) Guide to electroporation and electrofusion. Academic, Orlando, FL, pp 77–90Google Scholar
  43. 43.
    Neumann E, Kakorin S, Toensing K (1999) Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenerg 48:3–16CrossRefPubMedGoogle Scholar
  44. 44.
    Nicoloff Jac A (1995) Animal cell electroporation and electrofusion protocols. Humana, Totowa, NJGoogle Scholar
  45. 45.
    Pastushenko VF, Chizmadzhev YA, Arakelyan VB (1979) Electric breakdown of bilayer membranes: II. Calculation of the membrane lifetime in the steady-state diffusion approximation. Bioelectrochem Bioenerg 6:63–70CrossRefGoogle Scholar
  46. 46.
    Petrov AG, Mitov MD, Dershanki AI (1980) Edge energy and pore stability in bilayer lipid membranes. In: Bata L (eds) Advances in liquid crystal research and applications. Pergamon, Oxford, pp 695–737Google Scholar
  47. 47.
    Phez E, Faurie C, Golzio M, Teissie J, Rols M-P (2005) New insights in the visualization of membrane permeabilization and DNA/membrane interaction of cells submitted to electric pulses. Biochim Biophyis Acta 1724:248–254Google Scholar
  48. 48.
    Prausnitz MR, Bose VG, Langer R, Weaver JC (1993) Electroporation of mammalian skin: a mechanism to enhance trans-dermal drug delivery. Proc Natl Acad Sci USA 90:10504–10508PubMedCrossRefGoogle Scholar
  49. 49.
    Puc M, Kotnik T, Mir LM, Miklav ID (2003) Quantitative model of small molecules uptake after in vitro cell electropermeabilization. Bioelectrochemistry 60(1–2):1–10CrossRefPubMedGoogle Scholar
  50. 50.
    Sale AJH, Hamilton WA (1967) Effects of high fields on microorganisms: I. Killing of bacteria and yeasts. Biochim Biophys Acta 148:781–788Google Scholar
  51. 51.
    Sek WH (1992) Effects of pulse length and strength on electroporation efficiency. Animal cell electroporation and electrofusion protocols. Humana Press, Totowa, NJGoogle Scholar
  52. 52.
    Shane C (2005) Introductory biology, available at membranes/structure.html, Version 7.014Google Scholar
  53. 53.
    Sokirko AV (1994) Distribution of the electric field in an axially symmetric pore. Bioectrochem Bioenerg 33:25–30CrossRefGoogle Scholar
  54. 54.
    Stämpfli R (1958) Reversible electrical breakdown of the excitable membrane of a Ranvier node. Ann Acad Brazil Ciens 30:57–63Google Scholar
  55. 55.
    Steinchen A, Gallez D, Sanfield A (1982) J Colloid Interface Sci 85:5–12CrossRefGoogle Scholar
  56. 56.
    Stratton JA (1941) Electromagnetic theory. McGraw-Hill, New York, NYzbMATHGoogle Scholar
  57. 57.
    Sugar IP (1979) A theory of the electric field-induced phase-transition of phospholipid bilayers. Biochim Biophys Acta 556:72–85PubMedCrossRefGoogle Scholar
  58. 58.
    Suzuki T, Shin BC, Fujikura K, Matsuzaki T, Takata K (1998) Direct gene transfer into rat liver cells by in vivo electroporation. FEBS Lett 425:436–440CrossRefPubMedGoogle Scholar
  59. 59.
    Tarek M (2005) Membrane electroporation: a molecular dynamics simulation. Biophysical J 88:4045–4053CrossRefGoogle Scholar
  60. 60.
    Taupin C, Dvolaitzky, Sauterey C (1975) Osmotic pressure induced pores in phospholipid vesicles. Biochemistry 14:4771–4775CrossRefPubMedGoogle Scholar
  61. 61.
    Teissie J, Golzio M, Rols MP (2005) Mechanisms of cell membrane electropermeabilisation: a minireview of our present (lack of?) knowledge. Biochim Biophys Acta 1724:270–280PubMedGoogle Scholar
  62. 62.
    Tekle E, Astumian RD, Chock PB (1994) Selective and asymmetric molecular transport across electroporated cell membranes. Proc Natl Acad Sci USA 91:11512–11516PubMedCrossRefGoogle Scholar
  63. 63.
    Tieleman DP, Leontiadou H, Mark AE, Marrink SJ (2003) Molecular dynamics simulation of pore formation in phospholipid bilayers by mechanical force and electric fields. J Am Chem Soc 125:6382–6383CrossRefPubMedGoogle Scholar
  64. 64.
    Tien HT (1974) Bilayer lipid membranes. Marcel Dekker, New York, NYGoogle Scholar
  65. 65.
    Tien HT, Ottova A (2003) The bilayer lipid membrane (BLM) under electrical fields. IEEE Trans Dielectr Electr Insul 10:717–727CrossRefGoogle Scholar
  66. 66.
    Tsong TY (1987) Electric modification of membrane permeability for drug loading into living cells. Methods Enzymol 149:248–259PubMedGoogle Scholar
  67. 67.
    Weaver JC (1993) Electroporation: a general phenomenon for manipulating cells and tissues. J Cell Biochem 51:426–435PubMedGoogle Scholar
  68. 68.
    Weaver JC (2000) Electroporation of cells and tissues. IEEE Trans Plasma Sci 28:24–33CrossRefGoogle Scholar
  69. 69.
    Weaver JC (2003) Electroporation of biological membranes from multicellular to nano scales. IEEE Trans Dielectr Electr Insul 10(5):754–768CrossRefMathSciNetGoogle Scholar
  70. 70.
    Weaver JC, Mintzer RA (1981) Bilayer stability due to trans-membrane potentials. Phys Lett 86A:57–59Google Scholar
  71. 71.
    Weaver JC, Chizmadzhev YA (1996) Theory of electroporation: a review. Bioelectrochem Bioenerg 41:135–160CrossRefGoogle Scholar
  72. 72.
    Zimmermann U, Vienken J, Pilwat G (1980) Development of drug carrier systems: electrical field induced effects in cell membranes. Bioelectrochem Bioenerg 7:553CrossRefGoogle Scholar

Copyright information

© International Federation for Medical and Biological Engineering 2006

Authors and Affiliations

  1. 1.Department of ElectronicsUniversity of YorkYorkUK
  2. 2.Department of Medical Physics and Engineering, Leeds Teaching HospitalsSt. James’s University HospitalLeedsUK
  3. 3.Academic Unit of Medical PhysicsUniversity of LeedsLeedsUK

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