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Numerical Determination of Transmembrane Voltage Induced on Irregularly Shaped Cells

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Abstract

The paper presents an approach that reduces several difficulties related to the determination of induced transmembrane voltage (ITV) on irregularly shaped cells. We first describe a method for constructing realistic models of irregularly shaped cells based on microscopic imaging. This provides a possibility to determine the ITV on the same cells on which an experiment is carried out, and can be of considerable importance in understanding and interpretation of the data. We also show how the finite-thickness, nonzero-conductivity membrane can be replaced by a boundary condition in which a specific surface conductivity is assigned to the interface between the cell interior (the cytoplasm) and the exterior. We verify the results obtained using this method by a comparison with the analytical solution for an isolated spherical cell and a tilted oblate spheroidal cell, obtaining a very good agreement in both cases. In addition, we compare the ITV computed for a model of two irregularly shaped CHO cells with the ITV measured on the same two cells by means of a potentiometric fluorescent dye, and also with the ITV computed for a simplified model of these two cells.

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Notes

  1. This could be addressed by sequentially modifying the electric properties of the membrane and recomputing the potential distribution. An example of such modification for a tissue exposed to an electric field can be found in Ref.41

REFERENCES

  1. Alberts, B., D. Bray, J. Lewis, M. Raff, K. Roberts, and J. D. Watson. Molecular Biology of the Cell, 3rd edn., New York: Garland, 1994.

    Google Scholar 

  2. Bedlack, R. S., M. Wei, S. H. Fox, E. Gross, and L. M. Loew. Distinct electric potentials in soma and neurite membranes. Neuron 13:1187–1193, 1994.

    Article  PubMed  CAS  Google Scholar 

  3. Buitenweg, J. R., W. L. Rutten, and E. Marani. Geometry-based finite-element modeling of the electrical contact between a cultured neuron and a microelectrode. IEEE Trans. Biomed. Eng. 50:501–509, 2003.

    Article  PubMed  Google Scholar 

  4. Cheng, D. K. L., L. Tung, and E. A. Sobie. Nonuniform responses of transmembrane potential during electric field stimulation of single cardiac cells. Am. J. Physiol. 277:H351–H362, 1999.

    PubMed  CAS  Google Scholar 

  5. Fear, E. C., and M. A. Stuchly. Biological cells with gap junctions in low-frequency electric fields. IEEE Trans. Biomed. Eng. 45:856–866, 1998.

    Article  PubMed  CAS  Google Scholar 

  6. Fear, E. C., and M. A. Stuchly. Modeling assemblies of biological cells exposed to electric fields. IEEE Trans. Biomed. Eng. 45:1259–1271, 1998.

    Article  PubMed  CAS  Google Scholar 

  7. Gabriel, B., and J. Teissié. Fluorescence imaging in the millisecond time range of membrane electropermeabilization of single cell using a rapid ultra-low-light intensifying detection system. Eur. Biophys. J. 27:291–298, 1998.

    Article  CAS  Google Scholar 

  8. Gascoyne, P. R. C., R. Pethig, J. P. H. Burt, and F. F. Becker. Membrane changes accompanying the induced differentiation of Friend murine erythroleukemia cells studied by dielectrophoresis. Biochim. Biophys. Acta. 1146:119–126, 1993.

    Google Scholar 

  9. Gimsa, J., and D. Wachner. Analytical description of the transmembrane voltage induced on arbitrarily oriented ellipsoidal and cylindrical cells. Biophys. J. 81:1888–1896, 2001.

    PubMed  CAS  Google Scholar 

  10. Gimsa, J., and D. Wachner. On the analytical description of transmembrane voltage induced on spheroidal cells with zero membrane conductance. Eur. Biophys. J. 30:463–466, 2001.

    Article  PubMed  CAS  Google Scholar 

  11. Golzio, M., L. Mazzolini, P. Moller, M. P. Rols, and J. Teissie. Inhibition of gene expression in mice muscle by in vivo electrically mediated siRNA delivery. Gene Therapy 12:246–251, 2005.

    Article  PubMed  CAS  Google Scholar 

  12. Gowrishankar, T. R., and J. C. Weaver. An approach to electrical modeling of single and multiple cells. Proc. Natl. Acad. Sci. U.S.A. 100:3203–3208, 2003.

    Article  PubMed  CAS  Google Scholar 

  13. Gross, D., L. M. Loew, and W. Webb. Optical imaging of cell membrane potential changes induced by applied electric fields. Biophys. J. 50:339–348, 1986.

    PubMed  CAS  Google Scholar 

  14. Harris, C. M., and D. B. Kell. The radio-frequency dielectric properties of yeast cells measured with a rapid, automated, frequency-domain dielectric spectrometer. Bioelectrochem. Bioenerg. 11:15–28, 1983.

    Article  Google Scholar 

  15. Hassan, N., I. Chatterjee, N. G. Publicover, and G. L. Craviso. Mapping membrane-potential perturbations of chromaffin cells exposed to electric fields. IEEE Trans. Plasma Sci. 30:1516–1524, 2002.

    Article  Google Scholar 

  16. Heller, R., R. Gilbert, and M. J. Jaroszeski. Clinical applications of electrochemotherapy. Adv. Drug. Deliv. Rev. 35:119–129, 1999.

    Article  PubMed  CAS  Google Scholar 

  17. Hibino, M., H. Itoh, and K. Kinosita. Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. Biophys. J. 64:1789–1800, 1993.

    PubMed  CAS  Google Scholar 

  18. Hibino, M., M. Shigemori, H. Itoh, K. Nagayama, and K. Kinosita. Membrane conductance of an electroporated cell analyzed by submicrosecond imaging of transmembrane potential. Biophys. J. 59:209–220, 1991.

    PubMed  CAS  Google Scholar 

  19. Huang, X., D. Nguyen, D. W. Greve, and M. M. Domach. Simulation of microelectrode impedance changes due to cell growth. IEEE Sensors J. 4:576–583, 2004.

    Article  CAS  Google Scholar 

  20. Knisley, S. B., T. F. Blitchington, B. C. Hill, A. O. Grant, W. M. Smith, T. C. Pilkington, and R. E. Ideker. Optical measurements of transmembrane potential changes during electric field stimulation of ventricular cells. Circ. Res. 72:255–268, 1993.

    PubMed  CAS  Google Scholar 

  21. Kotnik, T., F. Bobanović, and D. Miklavčič. Sensitivity of transmembrane voltage induced by applied electric fields – a theoretical analysis. Bioelectrochem. Bioenerg. 43:285–291, 1997.

    Article  CAS  Google Scholar 

  22. Kotnik, T., and D. Miklavčič. Analytical description of transmembrane voltage induced by electric fields on spheroidal cells. Biophys. J. 79:670–679, 2000.

    PubMed  CAS  Google Scholar 

  23. Kotnik, T., and D. Miklavčič. Second-order model of membrane electric field induced by alternating external electric fields. IEEE Trans. Biomed. Eng. 47:1074–1081, 2000.

    Article  PubMed  CAS  Google Scholar 

  24. Lee, D. C., and W. M. Grill. Polarization of a spherical cell in a nonuniform extracellular electric field. Anal. Biomed. Eng. 33:603–615, 2005.

    Article  Google Scholar 

  25. Loew, L. M. Voltage sensitive dyes: Measurement of membrane potentials induced by DC and AC electric fields. Bioelectromagnetics Suppl. 1:179–189, 1992.

    Google Scholar 

  26. Lojewska, Z., D. L. Franks, B. Ehrenberg, and L. M. Loew. Analysis of the effect of medium and membrane conductance on the amplitude and kinetics of membrane potentials induced by externally applied electric fields. Biophys. J. 56:121–128, 1989.

    PubMed  CAS  Google Scholar 

  27. Miklavčič, D., G. Pucihar, M. Pavlovec, S. Ribarič, M. Mali, A. Maček-Lebar, M. Petkovšek, J. Nastran, S. Kranjc, M. Čemažar, and G. Serša. The effect of high frequency electric pulses on muscle contractions and antitumor efficiency in vivo for a potential use in clinical electrochemotherapy. Bioelectrochemistry 65:121–128, 2005.

    Article  PubMed  CAS  Google Scholar 

  28. Miller, C. E., and C. S. Henriquez. Three-dimensional finite element solution for biopotentials: Erythrocyte in an applied field. IEEE Trans. Biomed. Eng. 35:712–718, 1988.

    Article  PubMed  CAS  Google Scholar 

  29. Mir, L. M., and S. Orlowski. Mechanisms of electrochemotherapy. Adv. Drug Deliv. Rev. 35:107–118, 1999.

    Article  PubMed  CAS  Google Scholar 

  30. Montana, V., D. L. Farkas, and L. M. Loew. Dual-wavelength ratiometric fluorescence measurements of membrane-potential. Biochemistry 28:4536–4539, 1989.

    Article  PubMed  CAS  Google Scholar 

  31. Neumann, E., S. Kakorin, and K. Toensing. Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem. Bioenerg. 48:3–16, 1999.

    Article  PubMed  CAS  Google Scholar 

  32. Pavlin, M., N. Pavšelj, and D. Miklavčič. Dependence of induced transmembrane potential on cell density, arrangement, and cell position inside a cell system. IEEE Trans. Biomed. Eng. 49:605–612, 2002.

    Article  PubMed  Google Scholar 

  33. Pucihar, G., T. Kotnik, M. Kandušer, and D. Miklavčič. The influence of medium conductivity on electropermeabilization and survival of cells in vitro. Bioelectrochemistry 54:107–115, 2001.

    Article  PubMed  CAS  Google Scholar 

  34. Rols, M. P., C. Delteil, M. Golzio, and J. Teissié. Control by ATP and ADP of voltage-induced mammalian-cell-membrane permeabilization, gene transfer and resulting expression. Eur. J. Biochem. 254:382–388, 1998.

    Article  PubMed  CAS  Google Scholar 

  35. Schwan, H. P. Electrical properties of tissue and cell suspensions. Adv. Biol. Med. Phys. 5:147–209, 1957.

    PubMed  CAS  Google Scholar 

  36. Serša, G., M. Čemažar, and Z. Rudolf. Electrochemotherapy: advantages and drawbacks in treatment of cancer patients. Cancer Ther. 1:133–142, 2003.

    Google Scholar 

  37. Somiari, S., J. G. Malone, J. J. Drabick, R. A. Gilbert, R. Heller, M. J. Jaroszeski, and R. W. Malone. Theory and in vivo application of electroporative gene delivery. Mol. Ther. 2:178–187, 2000.

    Article  PubMed  CAS  Google Scholar 

  38. Stewart, D. A., T. R. Gowrishankar, and J. C. Weaver. Transport lattice approach to describing cell electroporation: use of a local asymptotic model. IEEE Trans. Plasma Sci. 32:1696–1708, 2004.

    Article  Google Scholar 

  39. Susil, R., D. Šemrov, and D. Miklavčič. Electric field induced transmembrane potential depends on cell density and organization. Electro. Magnetobiol. 17:391–399, 1998.

    Google Scholar 

  40. Šatkauskas, S., M. F. Bureau, M. Puc, A. Mahfoudi, D. Scherman, D. Miklavčič, and L. M. Mir. Mechanisms of in vivo DNA electrotransfer: respective contributions of cell electropermeabilization and DNA electrophoresis. Mol. Ther. 5:133–140, 2002.

    Article  PubMed  CAS  Google Scholar 

  41. Šel, D., D. Cukjati, D. Batiuskaite, T. Slivnik, L. M. Mir, and D. Miklavčič. Sequential finite element model of tissue electropermeabilization. IEEE Trans. Biomed. Eng. 52:816–827, 2005.

    Article  PubMed  Google Scholar 

  42. Teissie, J., and M. P. Rols. An experimental evaluation of the critical potential difference inducing cell membrane electropermeabilization. Biophys. J. 65:409–413, 1993.

    PubMed  CAS  Google Scholar 

  43. Teissié, J., N. Eynard, B. Gabriel, and M. P. Rols. Electropermeabilization of cell membranes. Adv. Drug Deliver Rev. 35:3–19, 1999.

    Article  Google Scholar 

  44. Tsong, T. Y. Electroporation of cell membranes. Biophys. J. 60:297–306, 1991.

    Article  PubMed  CAS  Google Scholar 

  45. Valič, B., M. Golzio, M. Pavlin, A. Schatz, C. Faurie, B. Gabriel, J. Teissié, M. P. Rols, and D. Miklavčič. Effect of electric field induced transmembrane potential on spheroidal cells: theory and experiment. Eur. Biophys. J. 32:519–528, 2003.

    Article  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

This work was supported by the Ministry of Higher Education, Science and Technology of the Republic of Slovenia. The authors wish to thank Dr Marko Puc for building the switcher device for delivery of electric pulses in the experiments.

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Correspondence to D. Miklavčič.

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Pucihar, G., Kotnik, T., Valič, B. et al. Numerical Determination of Transmembrane Voltage Induced on Irregularly Shaped Cells. Ann Biomed Eng 34, 642–652 (2006). https://doi.org/10.1007/s10439-005-9076-2

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  • DOI: https://doi.org/10.1007/s10439-005-9076-2

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