Study of Transmembrane Potentials of Inner and Outer Membranes Induced by Pulsed-Electric-Field Model and Simulation

A more proper and realistic multilayer dielectric model of spherical biological cell, in which nuclear was taken into consideration, was proposed based on the classic dielectric model in this paper. The general analytical method was also deduced and analyzed in detail in calculating the time courses of transmembrane potentials of both inner and outer membranes induced by constant and time-varying electric field. The time course of transmembrane potential of the outer membrane for multilayer dielectric model was compared to that of the classical model. It is shown that the latter is larger than the former, particularly for a cell with larger nuclear. The time courses of transmembrane potentials of both inner and outer membranes induced by pulsed electric fields (PEFs) with different durations were also studied based on the multilayer dielectric model. Long PEF targets outer membrane mainly, and there is little influence to cell nucleus, mitochondrion, and other organelles; thus, it causes electroporation to the outer membrane. As the pulse duration decreases, the electroporation effect changes gradually from the outer membrane to intracellular organelle membrane. Ultrashort PEF (tens of nanoseconds) induces larger voltage across the inner membrane and acts mostly on intracellular substructures. However, submicrosecond PEF (several hundreds of nanoseconds) can induce significant voltages across both the inner and outer membranes, therefore, causing damage to both the inner and outer membranes. This property of submicrosecond PEF has much practical value for tumor treatment.

[1]  H. Schwan Electrical properties of tissue and cell suspensions. , 1957, Advances in biological and medical physics.

[2]  S. Beebe,et al.  Nanosecond pulsed electric field effects on human cells , 2002, Conference Record of the Twenty-Fifth International Power Modulator Symposium, 2002 and 2002 High-Voltage Workshop..

[3]  H P Schwan,et al.  Cellular membrane potentials induced by alternating fields. , 1992, Biophysical journal.

[4]  Yuri Feldman,et al.  Study of normal and malignant white blood cells by time domain dielectric spectroscopy , 2001 .

[5]  Ravindra P. Joshi,et al.  Ultrashort electrical pulses open a new gateway into biological cells , 2004 .

[6]  Damijan Miklavcic,et al.  Second-order model of membrane electric field induced by alternating external electric fields , 2000, IEEE Transactions on Biomedical Engineering.

[7]  Caixin Sun,et al.  Experimental studies on Killing and inhibiting effects of steep pulsed electric field (SPEF) to target cancer cell and solid tumor , 2004 .

[8]  E Neumann,et al.  Fundamentals of electroporative delivery of drugs and genes. , 1999, Bioelectrochemistry and bioenergetics.

[9]  Damijan Miklavčič,et al.  Time course of transmembrane voltage induced by time-varying electric fields—a method for theoretical analysis and its application , 1998 .

[10]  Liao Ruijin,et al.  Experimental study on irreversible electrical breakdown of tumor cell under steep pulsed electric fields , 2002, Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology.

[11]  G. A. Hofmann,et al.  Medical applications of electroporation , 2000 .

[12]  James C. Weaver,et al.  Electroporation of cells and tissues , 2000 .

[13]  D Miklavcic,et al.  Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients. , 1998, European journal of cancer.

[14]  Ravindra P. Joshi,et al.  Modeling studies of cellular response to ultrashort, high-intensity electric fields , 2003, 2003 Annual Report Conference on Electrical Insulation and Dielectric Phenomena.

[15]  A. J. Compton The Electromagnetic Field , 1986 .

[16]  S. Orlowski,et al.  Mechanisms of electrochemotherapy. , 1999, Advanced drug delivery reviews.

[17]  Boris Rubinsky,et al.  Irreversible Electroporation: A New Ablation Modality — Clinical Implications , 2007, Technology in cancer research & treatment.

[18]  K. Schoenbach,et al.  Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition , 2001, PPPS-2001 Pulsed Power Plasma Science 2001. 28th IEEE International Conference on Plasma Science and 13th IEEE International Pulsed Power Conference. Digest of Papers (Cat. No.01CH37251).

[19]  E. Kieff,et al.  Electroporation of antibodies, DNA, and other macromolecules into cells: a highly efficient method. , 2000, Journal of immunological methods.

[20]  Alternating Field Evoked Membrane Potentials: Effects Of Membrane And Surface Conductance , 1990, [1990] Proceedings of the Twelfth Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[21]  Boris Rubinsky,et al.  In vivo results of a new focal tissue ablation technique: irreversible electroporation , 2006, IEEE Transactions on Biomedical Engineering.

[22]  Kenneth R. Foster,et al.  Thermal and nonthermal mechanisms of interaction of radio-frequency energy with biological systems , 2000 .

[23]  STUDY ON PRODUCTION OF NITRIC MONOXIDE FOR RESPIRATORY DISTRESS BY PULSED DISCHARGE , 2005 .

[24]  K. Schoenbach,et al.  Bioelectrics-new applications for pulsed power technology , 2001, PPPS-2001 Pulsed Power Plasma Science 2001. 28th IEEE International Conference on Plasma Science and 13th IEEE International Pulsed Power Conference. Digest of Papers (Cat. No.01CH37251).

[25]  K. Schoenbach,et al.  Energy-landscape-model analysis for irreversibility and its pulse-width dependence in cells subjected to a high-intensity ultrashort electric pulse. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.