Numerical study of the electroporation pulse shape effect on molecular uptake of biological cells

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Numerical study of the electroporation pulse shape effect on molecular uptake of biological cells

Background. In order to reduce the side-effects of chemotherapy, combined chemotherapy-electroporation (electrochemotherapy) has been suggested. Electroporation, application of appropriate electric pulses to biological cells, can significantly enhance molecular uptake of cells due to formation of transient pores in the cell membrane. It was experimentally demonstrated that the efficiency of electroporation is under the control of electric pulse parameters. However, the theoretical basis for these experimental results is not fully explained. In order to predict the outcome of experiments and optimize the efficiency of electroporation before each treatment, we developed a model to investigate the effect of pulse shape on efficiency of electroporation.

Results. Our model is based on a developed chemical-kinetics scheme and trapezium barrier model, while selfconsistency was taken into account. This model is further supplemented with a molecular transport model to acquire the molecular uptake of cells. The investigated pulse shapes in this study were unipolar rectangular pulses with different rise and fall times, triangular, sinusoidal and bipolar rectangular pulses and also sinusoidal modulated unipolar pulses with different percentages of modulation. The obtained results from our modelling and simulations are in good agreement with previously published experimental results.

Conclusions. We therefore conclude that this model can be used to predict the effects of arbitrarily shaped electroporation pulses on cell membrane conductivity and molecular transport across the cell membrane.

Airley R. Cancer Chemotherapy: Basic Science to the Clinic, West Sussex: Wiely-Blackwell; 2009.

Mir LM, Belehradek M, Domenge C, Orlowski S, Poddevin B, Belehradek J Jr, et al. Electrochemotherapy, a new antitumor treatment: first clinical trial. CR Acad Sci III 1991; 313: 613-8.

Tsong TY. Electroporation of cell membranes. Biophys J 1991; 60: 297-306.

Neumann E, Kakorin S, Toensing K. Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenergy 1999; 48: 3-16.

Teissie J, Eynard N, Gabriel B, Rols MP. Electropermeabilization of cell membranes. Adv Drug Del Rev 1999; 35: 3-19.

Neumann E, Kakorin S, Tönsing K. Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenerg 1999; 48: 3-16.

Mir LM. Bases and rationale of the electrochemotherapy. EJC Suppl 2006; 4: 38-44.

Sersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoj M. Electrochemotherapy in treatment of tumours. EJSO 2008; 34: 232-40.

Zupanic A, Corovic S, Miklavcic D. Optimization of electrode position and electric pulse amplitude in electrochemotherapy. Radiol Oncol 2008; 42: 93-101.

Faurie C, Golzio M, Phez E, Teissie J, Rols MP. Electric field induced cell membrane permeabilization and gene transfer: theory and experiments. Eng Life Sci 2005; 5: 179-86.

Teissie J, Eynard N, Vernhes MC, Bénichou A, Ganeva V, Galutzov B, et al. Recent biotechnological developments of electropulsation. A prospective review. Bioelectrochem 2002; 55: 107-12.

Golzio M, Mazzolini L, Moller P, Rols MP, Teissie J. Inhibition of gene expression in mice muscle by in vivo electrically mediated siRNA delivery. Gene Ther 2005; 12: 246-51.

Mesojednik S, Kamensek U, Cemazar M. Evaluation of shRNA-mediated gene silencing by electroporation in LPB fibrosarcoma cells. Radiol Oncol 2008; 42: 82-92.

Pliquett U, Weaver JC. Feasibility of an electrode-reservoir device for transdermal drug delivery by noninvasive skin electroporation. IEEE Trans Biomed Eng 2007; 54: 536-8.

Gothelf A, Mir LM, Gehl J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation, Cancer Treat Rev 2003; 29: 371-8.

Pavselj N, Miklavcic D. Numerical modeling in electroporation-based biomedical applications. Radiol Oncol 2008; 42: 159-68.

Teissie J, Escoffre JM, Rols MP, Golzio M. Time dependence of electric field effects on cell membranes. A review for a critical selection of pulse duration for therapeutical applications. Radiol Oncol 2008; 42: 196-206.

Rols MP, Teissie J. Electropermeabilization of mammalian cells to macromolecules: control by pulse duration. Biophys J 1998; 75: 1415-23.

Kotnik T, Pucihar G, Rebersek M, Mir LM, Miklavcic D. Role of pulse shape in cell membrane electropermeabilization. Biochim Biophys Acta 2003; 1614: 193-200.

Pucihar G, Mir LM, Miklavcic D. The effect of pulse repetition frequency on the uptake into electropermeabilized cells in vitro with possible applications in electrochemotherapy. Bioelectrochem 2002; 57: 167-72.

Macek-Lebar A, Sersa G, Kranjc S, Groselj A, Miklavcic D. Optimisation of pulse parameters in vitro for in vivo electrochemotherapy. Anticancer Res 2002; 22: 1731-6.

Macek-Lebar A, Miklavcic D. Cell electropermeabilization to small molecules in vitro: control by pulse parameters. Radiol Oncol 2001; 35: 193-202.

DeBruin KA, KrassowskaW. Modeling Electroporation in a Single Cell. II. Effects of Ionic Concentrations. Biophys J 1999; 77: 1225-33.

Gowrishankar TR, Weaver JC. An approach to electrical modeling of single and multiple cells. Proc Natl Acad Sci USA 2003; 100: 3203-8.

Joshi RP, Hu Q, Schoenbach KH, Bebe SJ. Simulations of electroporation dynamics and shape deformations in biological cells subjected to high voltage pulses. IEEE Trans Plasma Sci 2002; 30: 1536-46.

Joshi RP, Hu Q, Schoenbach KH. Modeling studies of cell response to ultrashort, high-intensity electric fields—implications for intracellular manipulation. IEEE Trans Plasma Sci 2004; 32: 1677-86.

Neu JC, Krassowska W. Asymptotic model of electroporation. Phys Rev E 1999; 59: 3471-82.

Kotnik T, Bobanovic F, Miklavcic D. Sensitivity of transmembrane voltage induced by applied electric fields - a theoretical analysis. Bioelectrochem Bioenerg 1997; 43: 285-91.

Neumann E, Toensing K, Kakorin S, Budde P, Frey J. Mechanism of electroporative dye uptake by mouse B cells. Biophys J 1998; 74: 98-108.

Böckmann RA, Groot BL, Kakorin S, Neumann E, Grubmüller H. Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations. Biophys J 2008; 95: 1837-50.

Kakorin S, Neumann E. Ionic conductivity of electroporated lipid bilayer membranes. Bioelectrochem 2002; 56: 163-6.

Pavlin M, Leben V, Miklavcic D. Electroporation in dense cell suspension - Theoretical and experimental analysis of ion diffusion and cell permeabilization. Biochim Biophys Acta 2007; 1770: 12-23.

Schmeer M, Seipp T, Pliquett U, Kakorin S, Neumann E. Mechanism for the conductivity changes caused by membrane electroporation of CHO cell - pellets. Phy Chem Chem Phys 2004; 6: 5564-74.

Glogauer M, Lee W, McCulloch CA. Induced endocytosis in human fibroblasts by electrical fields. Exp Cell Res 1993; 208: 232-40.

Rols MP, Femenia P, Teissié J. Long-lived macropinocytosis takes place in electropermeabilized mammalian cells. Biochem Biophys Res Commun 1995; 208: 26-38.

Zimmermann U, Schnettler R, Klöck G, Watzka H, Donath E, Glaser RW. Mechanisms of electrostimulated uptake of macromolecules into living cells. Naturwissenschaften 1990; 77: 543-5.

Puc M, Kotnik T, Mir LM, Miklavcic D. Quantitative model of small molecules uptake after in vitro cell electropermeabilization. Bioelectrochem 2003; 60: 1-10.

Pucihar G, Kotnik T, Valic B, Miklavcic D. Numerical determination of transmembrane voltage induced on irregularly shaped cells. Annals Biomed Eng 2006; 34: 642-52.

Kotnik T, Miklavcic D, Slivnik T. Time course of transmembrane voltage induced by time-varying electric fields - a method for theoretical analysis and its application. Bioelectrochem Bioenerg 1998; 45: 3-16.

Pucihar G, Kotnik T, Miklavcic D, Teissie J. Kinetics of transmembrane transport of small molecules into electropermeabilized cells. Biophys J 2008; 95: 2837-48.

Gowrishankar TR, Pliquett U, Lee RC. Dynamics of membrane sealing in transient electropermeabilization of skeletal muscle membranes. Ann NY Acad Sci 1999; 888: 195-210.

Hibino M, Itoh H, Kinosita K. Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. Biophys J 1993; 64:1789-800.

Chernomordik LV, Sukharev SI, Popov SV, Pastushenko VF, Sokirko AV, Abidor IG, et al. The electrical breakdown of cell and lipid membranes: the similarity of phenomenologies. Biochim Biophys Acta 1987; 902: 360-73.

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