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Analysis of cell membrane permeabilization mechanics and pore shape due to ultrashort electrical pulsing

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Abstract

Cell membrane permeabilization mechanics and the resulting shape of nanopores in response to electrical pulsing are probed based on a continuum approach. This has implications for electropermeabilization and cell membrane transport. It is argued that small pores resulting from high-intensity (~100 kV/cm), nanosecond pulsing would have an initial asymmetric shape. This would lead to asymmetric membrane current–voltage characteristics, at least at early times. The role of the cytoskeleton is ignored here, but can be expected to additionally contribute to such asymmetries. Furthermore, we show that the pore shape and membrane conduction would be dynamic, and evolve toward a symmetric characteristic over time. This duration has been shown to be in the micro-second range.

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References

  1. Abidor IG, Arakelyan VB, Chernomordik LV, Chizmadzhev YA, Pastuchenko VF, Tarasevich MR (1979) Electric breakdown of bilayer lipid membranes: main experimental facts and their qualitative discussion. Bioelectrochem Bioenerg 6:37–52

    Article  CAS  Google Scholar 

  2. Beckstein O, Sansom MSP (2004) The influence of geometry, surface character, and flexibility on the permeation of ions and water through biological pores. Phys Biol 1:42–52

    Article  CAS  PubMed  Google Scholar 

  3. Beebe SJ, Fox PM, Rec LJ, Willis EL, Schoenbach KH (2003) Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells. FASEB J 17:1493–1495

    CAS  PubMed  Google Scholar 

  4. Beebe SJ, Blackmore PF, White J, Joshi RP, Schoenbach KH (2004) Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms. Physiol Meas 25:1077–1093

    Article  PubMed  Google Scholar 

  5. Boal D (2002) Mechanics of the cell. Cambridge University Press, Cambridge

    Google Scholar 

  6. Born M (1920) Volumen und hydratationswarme der ionen. Z Phys 1:45–48

    Article  CAS  Google Scholar 

  7. Chen C, Smye SW, Robinson MP, Evans JA (2006) Membrane electroporation theories: a review. Med Biol Eng Comput 44:5–14

    Article  CAS  PubMed  Google Scholar 

  8. Denet AR, Preat V (2003) Transdermal delivery of timolol by electroporation through human skin. J Control Release 88:253–262

    Article  CAS  PubMed  Google Scholar 

  9. Deryagin BV, Gutop YV (1962) Theory of the breakdown (rupture) of free films. Kolloidn Zh 24:370–374

    Google Scholar 

  10. Evans E, Heinrich V, Ludwig F, Rawicz W (2003) Dynamic tension spectroscopy and strength of biomembranes. Biophys J 85:2342–2350

    Article  CAS  PubMed  Google Scholar 

  11. Farago O (2003) Water-free computer model for fluid bilayer membranes. J Chem Phys 119:596–605

    Article  CAS  Google Scholar 

  12. Farago O, Santangelo CD (2005) Pore formation in fluctuating membranes. J Chem Phys 122:044901-1–044901-9

    Google Scholar 

  13. Giaya A, Thompson RW (2002) Observations on an equation of state for water confined in narrow slit-pores. J Chem Phys 116:2565–2571

    Article  CAS  Google Scholar 

  14. Giaya A, Thompson RW (2002) Water confined in cylindrical micropores. J Chem Phys 117:3464–3475

    Article  CAS  Google Scholar 

  15. 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 940:275–287

    Article  CAS  PubMed  Google Scholar 

  16. Helfrich W (1973) Elastic properties of lipid bilayers—theory and possible experiments. Z Naturforsch 28:693–703

    CAS  Google Scholar 

  17. Helfrich W (1974) The size of bilayer vesicles generated by sonication. Phys Lett A 50:115–116

    Article  Google Scholar 

  18. Joshi RP, Hu Q, Aly R, Schoenbach KH, Hjalmarson HP (2001) Self-consistent simulations of electroporation dynamics in biological cells subjected to ultrafast electrical pulses. Phys Rev E 64:011913-1–011913-10

    Google Scholar 

  19. Joshi RP, Mishra A, Song J, Pakhomov A, Schoenbach KH (2008) Simulation studies of ultrashort, high-intensity electric pulse induced action potential block in whole-animal nerves. IEEE Trans Biomed Eng 55:1391–1398

    Article  PubMed  Google Scholar 

  20. Joshi RP, Song J, Sridhara V (2009) Aspects of lipid membrane bio-responses to subnanosecond, ultrahigh voltage pulsing. IEEE Trans Dielectr Electr Insulation 16:1243–1250

    Article  CAS  Google Scholar 

  21. Kubo R, Toda M, Hashitsume N (1991) Statistical physics II, 2nd edn. Springer-Verlag, Berlin

    Google Scholar 

  22. Lee RC, Kolodney MS (1987) Electrical injury mechanisms: dynamics of the thermal response. Plast Reconstr Surg 80:663–671

    Article  CAS  PubMed  Google Scholar 

  23. Levitt DG (1978) Mesoscopic undulations and thickness fluctuations in lipid bilayers from molecular dynamics simulations. Biophys J 22:209–219

    Article  CAS  PubMed  Google Scholar 

  24. Lin JH, Baumgaertner A (2000) Stability of a melittin pore in a lipid bilayer: a molecular dynamics study. Biophys J 78:1714–1724

    Article  CAS  PubMed  Google Scholar 

  25. Lindahl E, Edholm O (2000) Mesoscopic undulations and thickness fluctuations in lipid bilayers from molecular dynamics simulations. Biophys J 79:426–433

    Article  CAS  PubMed  Google Scholar 

  26. Litster JD (1975) Stability of lipid bilayers and red blood cell membranes. Phys Lett A 53:193–194

    Article  Google Scholar 

  27. Mali B, Jarm T, Corovic S, Paulin-Kosir MS, Cemazar M, Sersa G, Miklavcic D (2008) The effect of electroporation pulses on functioning of the heart. Med Biol Eng Comput 46:745–757

    Article  PubMed  Google Scholar 

  28. Melikov KC, Frolov VA, Shcherbakov A, Samsonov AV, Chizmadzhev YA (2001) Voltage-induced nonconductive pre-pores and metastable single pores in unmodified planar lipid bilayer. Biophys J 80:1829–1836

    Article  CAS  PubMed  Google Scholar 

  29. Mir LM, Orlowski S, Belehradek J Jr, Teissie J, Rols MP, Sersa G, Miklavcic D, Gilbert R, Heller R (1995) Biomedical applications of electric pulses with special emphasis on antitumour electrochemotherapy. Bioelectrochem Bioenerg 38:203–207

    Article  CAS  Google Scholar 

  30. Mir LM, Moller PH, Andre F, Gehl J (2005) Advances in genetics. Academic Press, New York, pp 83–114

    Google Scholar 

  31. Napotnik TB, Reberšek M, Kotnik T, Lebrasseur E, Cabodevila G, Miklavčič D (2010) Electropermeabilization of endocytotic vesicles in B16 F1 mouse melanoma cells. Med Biol Eng Comput 48:407–413

    Article  PubMed  Google Scholar 

  32. Neu JC, Krassowska W (2003) Modeling postshock evolution of large electropores. Phys Rev E 67:021915-1–021915-12

    Google Scholar 

  33. Neu JC, Krassowska W (2006) Singular perturbation analysis of the pore creation transient. Phys Rev E 74:031917-1–031917-9

    Google Scholar 

  34. Neu JC, Smith KC, Krassowska W (2003) Electrical energy required to form large conducting pores. Bioelectrochemistry 60:107–114

    Article  CAS  PubMed  Google Scholar 

  35. Neumann E, Sowers AE, Jordan CA (1989) Electroporation and electrofusion in cell biology. Plenum Press, New York

    Google Scholar 

  36. Neumann E, Kakorin S, Toensig K (1999) Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenerg 48:3–16

    Article  CAS  PubMed  Google Scholar 

  37. Nuccitelli R, Pliquett U, Chen X, Ford W, Swanson J, Beebe SJ, Kolb JF, Schoenbach KH (2006) Nanosecond pulsed electric fields cause melanomas to self-destruct. Biochem Biophys Res Commun 343:351–360

    Article  CAS  PubMed  Google Scholar 

  38. Pakhomov AG, Kolb JF, Joshi RP, Schoenbach KH, Dayton T, Comeaux J, Ashmore J, Beason C (2006) Neuromuscular disruption with ultrashort electrical pulses. Proc SPIE Int Soc Opt Eng 6219:621903–621910

    Google Scholar 

  39. Pakhomov AG, Shevin R, White JA, Kolb JF, Pakhomova ON, Joshi RP, Schoenbach KH (2007) Membrane permeabilization and cell damage by ultrashort electric field shocks. Arch Biochem Biophys 465:109–118

    Article  CAS  PubMed  Google Scholar 

  40. Pakhomov AG, Bowman AM, Ibey BL, Andre FM, Pakhomova ON, Schoenbach KH (2009) Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane. Biochem Biophys Res Comm 385:181–186

    Article  CAS  PubMed  Google Scholar 

  41. Parsegian A (1969) Energy of an ion crossing of a low dielectric membrane: solutions to four relevant electrostatic problems. Nature (London) 221:844–846

    Article  CAS  Google Scholar 

  42. Pastushenko VF, Chhizmadzhev YA (1982) Stabilization of conducting pores in BLM by electric current. Gen Physiol Biophys 1:43–52

    Google Scholar 

  43. Resat H, Mezei M (1994) Grand canonical Monte Carlo simulation of water positions in crystal hydrates. J Am Chem Soc 116:7451–7452

    Article  CAS  Google Scholar 

  44. Rols MP, Teissie J (1992) Experimental evidence for the involvement of the cytoskeleton in mammalian cell electropermeabilization. Biochim Biophys Acta 1111:45–50

    Article  CAS  PubMed  Google Scholar 

  45. Rosado JA, Gonzalez A, Salido GM, Pariente JA (2002) Effects of reactive oxygen species on actin filament polymerisation and amylase secretion in mouse pancreatic acinar cells. Cell Signal 14:547–556

    Article  CAS  PubMed  Google Scholar 

  46. Schoenbach KH, Beebe SJ, Buescher ES (2001) Intracellular effect of ultrashort electrical pulses. Bioelectromagnetics 22:440–448

    Article  CAS  PubMed  Google Scholar 

  47. Schoenbach KH, Joshi RP, Kolb J, Chen N, Stacey M, Blackmore P, Buescher ES, Beebe SJ (2004) Ultrashort electrical pulses open a new gateway into biological cells. Proc IEEE 92:1122–1137

    Article  CAS  Google Scholar 

  48. Schoenbach KH, Hargrave B, Joshi RP, Kolb JF, Nuccitelli R, Osgood C, Pakhomov A, Stacey M, Swanson RJ, White J, Xiao S, Zhang J, Beebe SJ, Blackmore PF, Buescher ES (2007) Bioelectric effects of intense nanosecond pulses. IEEE Trans Dielectr Electr Insulation 14:1088–1109

    Article  CAS  Google Scholar 

  49. Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by α-helical antimicrobial and cell non-selective membrane-lytic peptides. Biophys Biochim Acta 1462:55–70

    Article  CAS  Google Scholar 

  50. Siwy Z, Kosinska ID, Fulinski A, Martin CR (2005) Asymmetric diffusion through synthetic nanopores. Phys Rev Lett 94:048102-1–048102-4

    Google Scholar 

  51. Smith KC, Neu JC, Krassowska W (2004) Model of creation and evolution of stable macropores for DNA delivery. Biophys J 86:2813–2826

    Google Scholar 

  52. Sung W, Park PJ (1997) Polymer translocation through a pore in a membrane. Biophys J 73:1797–1804

    Article  CAS  PubMed  Google Scholar 

  53. Taupin C, Dvolaitzky M, Sauterey C (1975) Osmotic pressure induced pores in phospholipid vesicles. Biochemistry 14:4771–4775

    Article  CAS  PubMed  Google Scholar 

  54. Teissie J, Eynard N, Gabriel B, Rols MP (1999) Electropermeabilization of cell membranes. Adv Drug Deliv Rev 35:3–19

    Article  CAS  PubMed  Google Scholar 

  55. Tien HT, Ottova-Leitmannova A (2003) Planar lipid bilayers (BLMs) and their applications. Elsevier, Amsterdam, pp 917–961

    Google Scholar 

  56. Truskett TM, Debenedetti PG, Torquato S (2001) Thermodynamic implications of confinement for a waterlike fluid. J Chem Phys 114:2401–2418

    Article  CAS  Google Scholar 

  57. Vernier PT, Sun Y, Marcu L, Salemi S, Craft CM, Gundersen MA (2003) Calcium bursts induced by nanosecond electric field. Biochem Biophys Res Commun 310:286–295

    Article  CAS  PubMed  Google Scholar 

  58. Weaver JC (1994) Molecular basis for cell membrane electroporation. Ann N Y Acad Sci 720:141–152

    Article  CAS  PubMed  Google Scholar 

  59. Weaver JC, Chizmadzhev YA (1996) Theory of electroporation: a review. Bioelectrochem Bioenerg 41:135–160

    Article  CAS  Google Scholar 

  60. Weaver JC, Mintzer RA (1981) Decreased bilayer stability due to transmembrane potentials. Phys Lett A 86:57–59

    Article  Google Scholar 

  61. Wilhelm C, Winterhalter M, Zimmermann U, Benz R (1993) Kinetics of pore size during irreversible electrical breakdown of lipid bilayer membranes. Biophys J 64:121–128

    Article  CAS  PubMed  Google Scholar 

  62. Winterhalter M, Helfrich W (1987) Effect of voltage on pores in membranes. Phys Rev A 36:5874–5876

    Article  PubMed  Google Scholar 

  63. Wolf H, Rols MP, Boldt E, Neumann E, Teissie J (1994) Control by pulse parameters of electric field-mediated gene transfer in mammalian cells. Biophys J 66:524–531

    Article  CAS  PubMed  Google Scholar 

  64. Zemel A, Fattal DR, Ben-Shaul A (2003) Energetics and self-assembly of amphipathic peptide pores in lipid membranes. Biophys J 84:2242–2255

    Article  CAS  PubMed  Google Scholar 

  65. Zuckermann MJ, Heimburg T (2001) Insertion and pore formation driven by adsorption of proteins onto lipid bilayer membrane-water interfaces. Biophys J 81:2458–2472

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank A. Pakhomov (ODU) for useful discussions. Partial support from ORSP of Central Michigan University is also gratefully acknowledged.

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Correspondence to Ravindra P. Joshi.

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Joshi, R.P., Hu, Q. Analysis of cell membrane permeabilization mechanics and pore shape due to ultrashort electrical pulsing. Med Biol Eng Comput 48, 837–844 (2010). https://doi.org/10.1007/s11517-010-0659-1

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