Advertisement

Electroporation Theory

Concepts and Mechanisms
  • James C. Weaver
Part of the Methods in Molecular Biology™ book series (MIMB, volume 47)

Abstract

Application of strong electric field pulses to cells and tissue is known to cause some type of structural rearrangement of the cell membrane. Significant progress has been made by adopting the hypothesis that some of these rearrangements consist of temporary aqueous pathways (“pores”), with the electric field playing the dual role of causing pore formation and providing a local driving force for ionic and molecular transport through the pores. Introduction of DNA into cells in vitro is now the most common application. With imagination, however, many other uses seem likely. For example, in vitro electroporation has been used to introduce into cells enzymes, antibodies, and other biochemical reagents for intracellular assays; to load larger cells preferentially with molecules in the presence of many smaller cells; to introduce particles into cells, including viruses; to kill cells purposefully under otherwise mild conditions; and to insert membrane macromolecules into the cell membrane itself. Only recently has the exploration of in vivo electroporation for use with intact tissue begun. Several possible applications have been identified, viz. combined electroporation and anticancer drugs for improved solid tumor chemotherapy, localized gene therapy, transdermal drug delivery, and noninvasive extraction of analytes for biochemical assays.

Keywords

Electric Field Pulse Bilayer Membrane Molecular Transport Planar Membrane Transmembrane Voltage 
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.

References

  1. 1.
    Neumann, E., Sowers, A., and Jordan, C. (eds.) (1989) Electroporation and Electrofusion in Cell Biology. Plenum, New York.Google Scholar
  2. 2.
    Tsong, T. Y. (1991) Electroporation of cell membranes. Biophys. J. 60, 297–306.PubMedCrossRefGoogle Scholar
  3. 3.
    Chang, D. C., Chassy, B. M., Saunders, J. A., and Sowers, A. E. (eds.) (1992) Guide to Electroporation and Electrofusion. Academic.Google Scholar
  4. 4.
    Weaver, J. C. (1993) Electroporation: a general phenomenon for manipulating cells and tissue. J. Cell. Biochem. 51, 426–435.PubMedGoogle Scholar
  5. 5.
    Orlowski, S. and Mir, L. M. (1993) Cell electropermeabilization: a new tool for biochemical and pharmacological studies. Biochim. Biophys. Acta 1154, 51–63.PubMedGoogle Scholar
  6. 6.
    Weaver, J. C. (1994) Electroporation in cells and tissues: a biophysical phenomenon due to electromagnetic fields. Radio Sci. (in press).Google Scholar
  7. 7.
    Weaver, J. C. and Chizmadzhev, Y. A. Electroporation, in CRC Handbook of Biological Effects of Electromagnetic Fields, 2nd ed. (Polk, C. and Postow, E., eds.), CRC, Boca Raton (submitted).Google Scholar
  8. 8.
    Parsegian, V. A. (1969) Energy of an ion crossing a low dielectric membrane: solutions to four relevant electrostatic problems. Nature 221, 844–846.PubMedCrossRefGoogle Scholar
  9. 9.
    Zahn, M. (1979) Electromagnetic Field Theory: A Problems Solving Approach, Wiley, New York.Google Scholar
  10. 10.
    Abidor, I. G., Arakelyan, V. B., Chernomordik, L. V., Chizmadzhev, Yu. A., Pastushenko, V. F., and Tarasevich, M. R. (1979) Electric breakdown of bilayer membranes: I. The main experimental facts and their qualitative discussion. Bioelectrochem. Bioenerg. 6, 37–52.CrossRefGoogle Scholar
  11. 11.
    Pastushenko, V. F., Chizmadzhev, Yu. A., and Arakelyan, V. B. (1979) Electric breakdown of bilayer membranes: II. Calculation of the membrane lifetime in the steady-state diffusion approximation. Bioelectrochem. Bioenerg. 6, 53–62.CrossRefGoogle Scholar
  12. 12.
    Chizmadzhev, Yu. A., Arakelyan, V. B., and Pastushenko, V. F. (1979) Electric breakdown of bilayer membranes: III. Analysis of possible mechanisms of defect origin. Bioelectrochem. Bioenerg. 6, 63–70.CrossRefGoogle Scholar
  13. 13.
    Pastushenko, V. F., Chizmadzhev, Yu. A., and Arakelyan, V. B. (1979) Electric breakdown of bilayer membranes: IV. Consideration of the kinetic stage in the case of the single-defect membrane. Bioelectrochem. Bioenerg. 6, 71–79.CrossRefGoogle Scholar
  14. 14.
    Arakelyan, V. B., Chizmadzhev, Yu. A., and Pastushenko, V. F. (1979) Electric breakdown of bilayer membranes: V. Consideration of the kinetic stage in the case of the membrane containing an arbitrary number of defects. Bioelectrochem. Bioenerg. 6, 81–87.CrossRefGoogle Scholar
  15. 15.
    Pastushenko, V. F., Arakelyan, V. B., and Chizmadzhev, Yu. A. (1979) Electric breakdown of bilayer membranes: VI. A stochastic theory taking into account the processes of defect formation and death: membrane lifetime distribution function. Bioelectrochem. Bioenerg. 6, 89–95.CrossRefGoogle Scholar
  16. 16.
    Pastushenko, V. F., Arakelyan, V. B., and Chizmadzhev, Yu. A. (1979) Electric breakdown of bilayer membranes: VII. A stochastic theory taking into account the processes of defect formation and death: statistical properties. Bioelectrochem. Bioenerg. 6, 97–104.CrossRefGoogle Scholar
  17. 17.
    Litster, J. D. (1975) Stability of lipid bilayers and red blood cell membranes. Phys. Lett. 53A, 193,194.Google Scholar
  18. 18.
    Taupin, C., Dvolaitzky, M., and Sauterey, C. (1975) Osmotic pressure induced pores in phospholipid vesicles. Biochemistry 14, 4771–4775.PubMedCrossRefGoogle Scholar
  19. 19.
    Powell, K. T., Derrick, E. G., and Weaver, J. C. (1986) A quantitative theory of reversible electrical breakdown. Bioelectrochem. Bioelectroenerg. 15, 243–255.CrossRefGoogle Scholar
  20. 20.
    Weaver, J. C. and Barnett, A. (1992) Progress towards a theoretical model of electroporation mechanism: membrane electrical behavior and molecular transport, in Guide to Electroporation and Electrofusion (Chang, D. C., Chassy, B. M., Saunders, J. A., and Sowers, A. E., eds.), Academic.Google Scholar
  21. 21.
    Barnett, A. and Weaver, J. C. (1991) Electroporation: a unified, quantitative theory of reversible electrical breakdown and rupture. Bioelectrochem. Bioenerg. 25, 163–182.CrossRefGoogle Scholar
  22. 22.
    Freeman, S. A., Wang, M. A., and Weaver, J. C. (1994) Theory of electroporation for a planar bilayer membrane: predictions of the fractional aqueous area, change in capacitance and pore-pore separation. Biophysical J. 67, 42–56.CrossRefGoogle Scholar
  23. 23.
    Renkin, E. M. (1954) Filtration, diffusion and molecular sieving through porous cellulose membranes. J. Gen. Physiol. 38, 225–243.PubMedGoogle Scholar
  24. 24.
    Wang, M. A., Freeman, S. A., Bose, V. G., Dyer, S., and Weaver, J. C. (1993) Theoretical modelling of electroporation: electrical behavior and molecular transport, in Electricity and Magnetism in Biology and Medicine (Blank, M., ed.), San Francisco, pp. 138–140.Google Scholar
  25. 25.
    Weaver, J. C. and Mintzer, R. A. (1981) Decreased bilayer stability due to transmembrane potentials. Phys. Lett. 86A, 57–59.Google Scholar
  26. 26.
    Benz, R., Beckers, F., and Zimmermann, U. (1979) Reversible electrical breakdown of lipid bilayer membranes: a charge-pulse relaxation study. J. Membrane Biol. 48, 181–204.CrossRefGoogle Scholar
  27. 27.
    Pastushenko, V. F. and Chizmadzhev, Yu. A. (1982) Stabilization of conducting pores in BLM by electric current. Gen. Physiol. Biophys. 1, 43–52.Google Scholar
  28. 28.
    Sugar, I. P. and Neumann, E. (1984) Stochastic model for electric field-induced membrane pores: electroporation. Biophys. Chemistry 19, 211–225.CrossRefGoogle Scholar
  29. 29.
    Weaver, J. C., Harrison, G. I., Bliss, J. G., Mourant, J. R., and Powell, K. T. (1988) Electroporation: high frequency of occurrence of the transient high permeability state in red blood cells and intact yeast. FEBS Lett. 229, 30–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Tsoneva, I., Tomov, T., Panova, I., and Strahilov, D. (1990) Effective production by electrofusion of hybridomas secreting monodonal antibodies against Hc-antigen of Salmonella. Bioelectrochem. Bioenerg. 24, 41–49.CrossRefGoogle Scholar
  31. 31.
    Weaver, J. C. (1993) Electroporation: a dramatic, nonthermal electric field phenomenon, in Electricity and Magnetism in Biology and Medicine (Blank, M., ed.), San Francisco, pp. 95–100.Google Scholar
  32. 32.
    Chernomordik, L. V., Sukharev, S. I., Abidor, I. G., and Chizmadzhev, Yu. A. (1982) The study of the BLM reversible electrical breakdown mechanism in the presence of UO2 2+. Bioelectrochem. Bioenerg. 9, 149–155.CrossRefGoogle Scholar
  33. 33.
    Neumann, E. and Rosenheck, K. (1972) Permeability changes induced by electric impulses in vesicular membranes. J. Membrane Biol. 10, 279–290.CrossRefGoogle Scholar
  34. 34.
    Kinosita, K. Jr. and Tsong, T. Y. (1978) Survival of sucrose-loaded erythrocytes in circulation. Nature 272, 258–260.PubMedCrossRefGoogle Scholar
  35. 35.
    Klenchin, V. A., Sukharev, S. I., Serov, S. M., Chernomordik, L. V., and Chizmadzhev, Yu. A. (1991) Electrically induced DNA uptake by cells is a fast process involving DNA electrophoresis. Biophys. J. 60, 804–811.PubMedCrossRefGoogle Scholar
  36. 36.
    Sukharev, S. I., Klenchin, V. A., Serov, S. M., Chernomordik, L. V., and Chizmadzhev, Y. A. (1992) Electroporation and electrophoretic DNA transfer into cells. Biophys. J. 63, 1320–1327.PubMedCrossRefGoogle Scholar
  37. 37.
    Prausnitz, M. R., Lau, B. S., Milano, C. D., Conner, S., Langer, R., and Weaver, J. C. (1993) A quantitative study of electroporation showing a plateau in net molecular transport. Biophys. J. 65, 414–422.PubMedCrossRefGoogle Scholar
  38. 38.
    Prausnitz, M. R., Milano, C. D., Gimm, J. A., Langer, R., and Weaver, J. C. (1994) Quantitative study of molecular transport due to electroporation: uptake of bovine serum albumin by human red blood cell ghosts. Biophys. J. 66, 1522–1530.PubMedCrossRefGoogle Scholar
  39. 39.
    Gift, E. A. and Weaver, J. C. (1995) Observation of extremely heterogeneous electroporative uptake which changes with electric field pulse amplitude in Saccharomyces cerevisiae. Biochim. Biophys. Acta 1234(1), 52–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Hui, L., Gift, E. A., and Weaver, J. C. Uptake of Bovine Serum Albumin by Yeast due to Electroporation: Existence of a Plateau as Pulse Amplitude is Increased (in preparation)Google Scholar
  41. 41.
    Lillie (1958) Glass, in Handbook of Physics (Condon, E. U. and Odishaw, H., eds.), McGraw-Hill, New York, pp. 8–83, 8–107Google Scholar
  42. 42.
    Neumann, E., Sprafke, A., Boldt, E., and Wolf, H. (1992) Biophysical digression on membrane electroporation, in Guide to Electroporation and Electrofusion (Chang, D. C., Chassy, B. M., Saunders, J. A., and Sowers, A. E., eds.), Academic.Google Scholar
  43. 43.
    Lee, R. C., River, L. P., Pan, F.-S., Ji, L., and Wollmann, R. L. (1992) Surfactant induced sealing of electropermeabilized skeletal muscle membranes in vivo. Proc. Natl. Acad. Sci. USA 89, 4524–4528.PubMedCrossRefGoogle Scholar
  44. 44.
    Gift, E. A. and Weaver, J. C. (1993) Cell survival following electroporation: quantitative assessment using large numbers of microcolonies, in Electricity and Magnetism in Biology and Medicine (Blank, M., ed.), San Francisco, pp. 147–150.Google Scholar
  45. 45.
    Weaver, J. C., Bliss, J. G., Powell, K. T., Harrison, G. I., and Williams, G. B. (1991) Rapid clonal growth measurements at the single-cell level: gel micro-droplets and flow cytometry. Bio/Technology 9, 873–877.PubMedCrossRefGoogle Scholar
  46. 46.
    Weaver, J. C., Bliss, J. G., Harrison, G. I., Powell, K. T., and Williams, G. B. (1991) Microdrop technology: a general method for separating cells by function and composition. Methods 2, 234–247.CrossRefGoogle Scholar
  47. 47.
    Weaver, J. C. (1994) Molecular basis for cell membrane electroporation. Ann. NY Acad. Sci. 720, 141–152.PubMedCrossRefGoogle Scholar
  48. 48.
    Okino, M. and Mohri, H. (1987) Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn. J. Cancer Res. 78, 1319–1321.PubMedGoogle Scholar
  49. 49.
    Mir, L. M., Orlowski, S., Belehradek, J., Jr., and Paoletti, C. (1991) In vivo potentiation of the bleomycin cytotoxicity by local electric pulses. Eur. J. Cancer 27, 68–72.PubMedCrossRefGoogle Scholar
  50. 50.
    Dev, S. B. and Hofmann, G. A. (1994) Electrochemotherapy—a novel method of cancer treatment. Cancer Treatment Rev. 20, 105–115.CrossRefGoogle Scholar
  51. 51.
    Prausnitz, M. R., Bose, V. G., Langer, R. S., and Weaver, J. C. (1992) Transdermal drug delivery by electroporation. Abstract, Proc. Intern. Symp. Control. Rel. Bioact. Mater. 19, Controlled Release Society, July 26–29, Orlando, FL, pp. 232,233.Google Scholar
  52. 52.
    Prausnitz, M. R., Bose, V. G., Langer, R., and Weaver, J. C. (1993) Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery. Proc. Natl. Acad. Sci. USA 90, 10,504–10,508.PubMedCrossRefGoogle Scholar
  53. 53.
    Titomirov, A. V., Sukharev, S., and Kistoanova, E. (1991) In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim. Biophys. Acta 1088, 131–134.PubMedGoogle Scholar
  54. 54.
    Sukharev, S. I., Titomirov, A. V., and Klenchin, V. A. (1994) Electrically-induced DNA transfer into cells Electrotransfection in vivo, in Gene Therapeutics (Wolff, J. A., ed.), Birkhäuser, Boston, pp. 210–232.Google Scholar
  55. 55.
    Gaylor, D. C., Prakah-Asante, K., and Lee, R. C. (1988) Significance of cell size and tissue structure in electrical Trauma. J. Theor. Biol. 133, 223–237.PubMedCrossRefGoogle Scholar
  56. 56.
    Bhatt, D. L., Gaylor, D. C, and Lee, R. C. (1990) Rhabdomyolysis due to pulsed electric fields. Plast. Reconstr. Surg. 86, 1–11.PubMedGoogle Scholar
  57. 57.
    Hughes, K. and Crawford, N. (1989) Reversible electropermeabilisation of human and rat blood platelets: evaluation of morphological and functional integrity “in vitro” and “in vivo.” Biochim. Biophys. Acta 981, 277–287.PubMedCrossRefGoogle Scholar
  58. 58.
    Mouneimne, Y., Tosi, P.-F., Barhoumi, R., and Nicolau, C. (1991) Biochim. Biophys. Acta 1066, 83–89.PubMedCrossRefGoogle Scholar
  59. 59.
    Zeira, M., Tosi, P.-F., Mouneimne, Y., Lazarte, J., Sneed, L., Volsky, D. J, and Nicolau, C. (1991) Proc. Natl. Acad. Sci. USA 88, 4409–4413.PubMedCrossRefGoogle Scholar
  60. 60.
    Belehradek, M., Domenge, C., Orlowski, S., Belehradek, J, Jr., and Mir, L. M. (1993) Cancer 72, 3694–3700.PubMedCrossRefGoogle Scholar
  61. 61.
    Riviele, J. E., Monterio-Riviere, N. A., Rogers, R. A., Bommannan, D., Tamada, J. A., and Potts, R. O. Pulsatile Transdermal Delivery of LHRH Using Electroporation: Drug Delivery and Skin Toxicology (submitted).Google Scholar
  62. 62.
    Potts, R. O. and Francoeur, M. L. (1990) Lipid biophysics of water loss through the skin. Proc. Natl. Acad. Sci. USA 87, 3871–3873.PubMedCrossRefGoogle Scholar
  63. 63.
    Bach, D. and Miller, I. R. (1980) Glyceryl monooleate black lipid membranes obtained from squalene solutions. Biophys. J. 29, 183–188.PubMedCrossRefGoogle Scholar
  64. 64.
    Sugar, I. P. (1981) The effects of external fields on the structure of lipid bilayers. J Physiol. Paris 77, 1035–1042.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1995

Authors and Affiliations

  • James C. Weaver
    • 1
  1. 1.Harvard-MIT Division of Health Sciences and TechnologyMassachusetts Institute of TechnologyCambridge

Personalised recommendations