Critical Electric Field and Transmembrane Voltage for Lipid Pore Formation in Experiments

Living reference work entry


Electropermeabilization is the result of exposure of cells to electric field pulses. The field pulse lasts from submicro- to several milliseconds. The field intensity should be large enough to induce a dramatic structural local alteration of the cell membrane organization. This results in transiently increased permeabilization of the target cell membrane. Due to the dielectric properties of the cell membrane, the external field induces a transmembrane voltage (TMV) which is controlled by size distribution in a population of cells. In most experiments, permeabilization is detected only when cell is exposed to a critical field strength. This is associated to a critical TMV that affects a subpopulation among the treated cells. This chapter describes the approaches to associate external field and induced TMV. The definition of the critical TMV is discussed.

The different assays (conductance, transport) are described with the critical consideration of their sensitivity for the definition of a threshold. The resulting different estimations of the critical TMV are then reported for the different assays and systems. The information provided by lipid assemblies, the simplest system, is then described as a guide for the effects of chemical and biochemical modifications of cell membranes. But the final conclusions remain that cell membrane electropermeabilization is indeed a complex process and its molecular characterization remains an intense field of investigations.


Membrane Transmembrane voltage Transport Membrane structure 



Research was conducted in the scope of the EBAM European Associated Laboratory (LEA) and resulted from the networking efforts of the COST Action TD1104 (


  1. Chen W, Lee RC (1994) Altered ion channel conductance and ionic selectivity induced by large imposed membrane potential pulse. Biophys J 67(2):603–612CrossRefGoogle Scholar
  2. Frey W, White JA, Price RO, Blackmore PF, Joshi RP, Nuccitelli R, Beebe SJ, Schoenbach KH, Kolb JF (2006) Plasma membrane voltage changes during nanosecond pulsed electric field exposure. Biophys J 90(10):3608–3615CrossRefGoogle Scholar
  3. Hibino M, Shigemori M, Itoh H, Nagayama K, Kinosita K Jr (1991) Membrane conductance of an electroporated cell analyzed by submicrosecond imaging of transmembrane potential. Biophys J 59(1):209–220CrossRefGoogle Scholar
  4. Hibino M, Itoh H, Kinosita K Jr (1993) Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. Biophys J 64(6):1789–1800CrossRefGoogle Scholar
  5. Kinosita K Jr, Tsong TT (1977) Hemolysis of human erythrocytes by transient electric field. Proc Natl Acad Sci USA 74(5):1923–1927CrossRefGoogle Scholar
  6. Kotnik T, Miklavčič D (2000) Analytical description of transmembrane voltage induced by electric fields on spheroidal cells. Biophys J 79:670–679CrossRefGoogle Scholar
  7. Kotnik T, Mir LM, Flisar K, Puc M, Miklavcic D (2001) Cell membrane electropermeabilization by symmetrical bipolar rectangular pulses. Part I Increased efficiency of permeabilization. Bioelectrochemistry 54(1):83–90CrossRefGoogle Scholar
  8. Kramar P, Delemotte L, Maček Lebar A, Kotulska M, Tarek M, Miklavčič D (2012) Molecular-level characterization of lipid membrane electroporation using linearly rising current. J Membr Biol 245(10):651–659. doi:10.1007/s00232-012-9487-6CrossRefGoogle Scholar
  9. Malinin VS, Sharov VS, Putvinsky AV, Osipov AN, Vladimirov YA (1989) Chemiluminescent reactions of phagocytes induced by electroporation: the role of Ca*+ and Mg *+ ions. Bioelectrochem Bioenergetics 22:37–44CrossRefGoogle Scholar
  10. Mauroy C, Rico-Lattes I, Teissié J, Rols MP (2015) Electric destabilization of supramolecular lipid vesicles subjected to fast electric pulses. Langmuir 31(44):12215–12222. doi:10.1021/acs.langmuir.5b03090CrossRefGoogle Scholar
  11. 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(4):1829–1836CrossRefGoogle Scholar
  12. Needham D, Hochmuth RM (1989) Electro-mechanical permeabilization of lipid vesicles. Role of membrane tension and compressibility. Biophys J 55(5):1001–1009CrossRefGoogle Scholar
  13. Neumann E, Kakorin S, Toensing K (1999) Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenerg 48(1):3–16CrossRefGoogle Scholar
  14. Pavlin M, Kandušer M, Reberšek M, Pucihar G, Hart FX, Magjarević R, Miklavčič D (2005) Effect of cell electroporation on the conductivity of a cell suspension. Biophys J 88:4378–4390CrossRefGoogle Scholar
  15. Pucihar G, Kotnik T, Valic B, Miklavcic D (2006) Numerical determination of transmembrane voltage induced on irregularly shaped cells. Ann Biomed Eng 34(4):642–652CrossRefGoogle Scholar
  16. Rems L, Miklavcic D (2016) Tutorial: electroporation of cells in complex materials and tissue. J Appl Phys 119:201101. doi:10.1063/1.4949264CrossRefGoogle Scholar
  17. Ryttsen F, Farre C, Brennan C, Weber SG, Nolkrantz K, Jardemark K, Chiu DT, Orwar O (2000) Characterization of single-cell electroporation by using patch-clamp and fluorescence microscopy. Biophys J 79:1993–2001CrossRefGoogle Scholar
  18. Teissie J, Tsong TY (1981) Electric field induced transient pores in phospholipid bilayer vesicles. Biochemistry 20(6):1548–1554CrossRefGoogle Scholar
  19. Teissié J, Rols MP (1993) An experimental evaluation of the critical potential difference inducing cell membrane electropermeabilization. Biophys J 65(1):409–413CrossRefGoogle Scholar
  20. Teissie J, Golzio M, Rols MP (2005) Mechanisms of cell membrane electropermeabilization: a minireview of our present (lack of ?) knowledge. Biochim Biophys Acta 1724(3):270–280CrossRefGoogle Scholar
  21. Towhidi L, Kotnik T, Pucihar G, Firoozabadi SM, Mozdarani H, Miklavcic D (2008) Variability of the minimal transmembrane voltage resulting in detectable membrane electroporation. Electromagn Biol Med 27(4):372–385. doi:10.1080/15368370802394644CrossRefGoogle Scholar
  22. Troiano GC, Tung L, Sharma V, Stebe KJ (1998) The reduction in electroporation voltages by the addition of a surfactant to planar lipid bilayers. Biophys J 75(2):880–888CrossRefGoogle Scholar
  23. Troiano GC, Stebe KJ, Raphael RM, Tung L (1999) The effects of gramicidin on electroporation of lipid bilayers. Biophys J 76(6):3150–3157CrossRefGoogle Scholar
  24. Tung L, O’Neill RJ (1995) Comparison of electroporation thresholds of cardiac cell membranes by rectangular and exponential pulses IEEE-EMBC and CMBEC Theme 1: Cardiovascular System Engineering in Medicine and Biology Society, IEEE 17th Annual Conference 251–252. doi: 10.1109/IEMBS.1995.575095Google Scholar
  25. Wegner LH, Frey W, Schönwälder S (2013) A critical evaluation of whole cell patch clamp studies on electroporation using the voltage sensitive dye ANNINE-6. Bioelectrochemistry 92:42–46. doi:10.1016/j.bioelechem.2013.03.002CrossRefGoogle Scholar
  26. Zimmermann U, Pilwat G, Riemann F (1974) Dielectric breakdown of cell membranes. Biophys J 14(11):881–899CrossRefGoogle Scholar
  27. Zimmermann U, Pilwat G, Holzapfel C, Rosenheck K (1976) Electrical hemolysis of human and bovine red blood cells. J Membr Biol 30(2):135–152CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institut de Pharmacologie et de Biologie StructuraleUniversité de Toulouse, CNRS, UPSToulouseFrance

Personalised recommendations