Energy-landscape-model analysis for irreversibility and its pulse-width dependence in cells subjected to a high-intensity ultrashort electric pulse.

We provide a simple, but physical analysis for cell irreversibility and apoptosis in response to an ultrashort (nanosecond), high-intensity electric pulse. Our approach is based on an energy landscape model for determining the temporal evolution of the configurational probability function p(q). The primary focus is on obtaining qualitative predictions of a pulse width dependence to apoptotic cell irreversibility that has been observed experimentally. The analysis couples a distributed electrical model for current flow with the Smoluchowski equation to provide self-consistent, time-dependent transmembrane voltages. The model captures the essence of the experimentally observed pulse-width dependence, and provides a possible physical picture that depends only on the electrical trigger. A number of interesting features are predicted.

[1]  F Bezanilla,et al.  Kramers' diffusion theory applied to gating kinetics of voltage-dependent ion channels. , 1999, Biophysical journal.

[2]  E. Perozo,et al.  Structural rearrangements underlying K+-channel activation gating. , 1999, Science.

[3]  Francisco Bezanilla,et al.  Fast gating in the Shaker K+ channel and the energy landscape of activation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[4]  L. Chernomordik,et al.  The electrical breakdown of cell and lipid membranes: the similarity of phenomenologies. , 1987, Biochimica et biophysica acta.

[5]  Stephen M. Goodnick,et al.  Fullband Particle-Based Simulation of High-Field Transient Transport in III–V Semiconductors , 2002 .

[6]  Ulrich Bruggemann,et al.  Low‐oxygen‐affinity red cells produced in a large‐volume, continuous‐ flow electroporation system , 1995, Transfusion.

[7]  U. Zimmermann,et al.  Reversibler dielektrischer Durchbruch von Zellmembranen in elektrostatischen Feldern / Reversible Dielectric Breakdown of Cell Membranes by Electrostatic Fields , 1974 .

[8]  D. Volsky,et al.  Full-length CD4 electroinserted in the erythrocyte membrane as a long-lived inhibitor of infection by human immunodeficiency virus. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H. Mekid,et al.  In vivo cell electrofusion , 2000, Biochimica et Biophysica Acta (BBA) - General Subjects.

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

[11]  J. Onuchic,et al.  Navigating the folding routes , 1995, Science.

[12]  Wolynes,et al.  Correlated energy landscape model for finite, random heteropolymers. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[13]  Mathias Winterhalter,et al.  Stabilization of planar lipid membranes: A stratified layer approach , 2000 .

[14]  Ravindra P. Joshi,et al.  Bacterial decontamination of liquids with pulsed electric fields , 2000 .

[15]  U. Karsten,et al.  Direct comparison of electric field-mediated and PEG-mediated cell fusion for the generation of antibody producing hybridomas. , 1988, Hybridoma.

[16]  G. Kroemer,et al.  Mitochondria as regulators of apoptosis: doubt no more. , 1998, Biochimica et biophysica acta.

[17]  S. Ang,et al.  Spatial and temporal ‘knock down’ of gene expression by electroporation of double-stranded RNA and morpholinos into early postimplantation mouse embryos , 2002, Mechanisms of Development.

[18]  B. Chait,et al.  The structure of the potassium channel: molecular basis of K+ conduction and selectivity. , 1998, Science.

[19]  J. Mazat,et al.  From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. , 1998, Biochimica et biophysica acta.

[20]  F Elinder,et al.  The screw–helical voltage gating of ion channels , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[21]  C. Nevison,et al.  Closing the global N2O budget: nitrous oxide emissions through the agricultural nitrogen cycle , 1998, Nutrient Cycling in Agroecosystems.

[22]  M. Prausnitz,et al.  Assessing the potential of skin electroporation for the delivery of protein- and gene-based drugs. , 1998, Trends in biotechnology.

[23]  J Teissié,et al.  Specific electropermeabilization of leucocytes in a blood sample and application to large volumes of cells. , 1990, Biochimica et biophysica acta.

[24]  L. Scorrano,et al.  On the Voltage Dependence of the Mitochondrial Permeability Transition Pore , 1997, The Journal of Biological Chemistry.

[25]  K. Schoenbach,et al.  Nanosecond, high‐intensity pulsed electric fields induce apoptosis in human cells , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  R P Joshi,et al.  Improved energy model for membrane electroporation in biological cells subjected to electrical pulses. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[27]  Physical model of voltage sensing in sodium channels based on the sliding helix complex. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[28]  R. Benz.  Structural requirement for the rapid movement of charged molecules across membranes. Experiments with tetraphenylborate analogues. , 1988, Biophysical journal.

[29]  L. Scorrano,et al.  The Mitochondrial Permeability Transition, Release of Cytochrome c and Cell Death , 2001, The Journal of Biological Chemistry.

[30]  H. Hülsheger,et al.  Killing of bacteria with electric pulses of high field strength , 1981, Radiation and environmental biophysics.

[31]  S. Singer,et al.  The Fluid Mosaic Model of the Structure of Cell Membranes , 1972, Science.

[32]  R. Benz,et al.  Kinetics of pore size during irreversible electrical breakdown of lipid bilayer membranes. , 1993, Biophysical journal.

[33]  S. Chandrasekhar.  Stochastic problems in Physics and Astronomy , 1943 .

[34]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[35]  W. Hamilton,et al.  Effects of high electric fields on microorganisms: I. Killing of bacteria and yeasts , 1967 .

[36]  J Teissié,et al.  Electrofusion: a biophysical modification of cell membrane and a mechanism in exocytosis. , 2000, Biochimie.

[37]  L. Mir,et al.  Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. , 1991, European journal of cancer.

[38]  W. Catterall,et al.  Structure and function of voltage-sensitive ion channels. , 1988, Science.

[39]  J. Onuchic,et al.  DIFFUSIVE DYNAMICS OF THE REACTION COORDINATE FOR PROTEIN FOLDING FUNNELS , 1996, cond-mat/9601091.

[40]  K. Schoenbach,et al.  Intracellular effect of ultrashort electrical pulses , 2001, Bioelectromagnetics.

[41]  K. Schoenbach,et al.  The effect of pulsed electric fields on biological cells: experiments and applications , 1997 .

[42]  H. Guy,et al.  Molecular model of the action potential sodium channel. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Leslie Tung,et al.  Electroporation‐mediated gene transfer in cardiac tissue , 1998, FEBS letters.

[44]  Owe Orwar,et al.  Single-cell electroporation. , 2003, Current opinion in biotechnology.

[45]  B. M. Fulk.  MATH , 1992 .

[46]  K. Schoenbach,et al.  The effects of intense submicrosecond electrical pulses on cells. , 2003, Biophysical journal.

[47]  N Crawford,et al.  Reversible electropermeabilisation of human and rat blood platelets: evaluation of morphological and functional integrity 'in vitro' and 'in vivo'. , 1989, Biochimica et biophysica acta.

[48]  C. Brenner,et al.  The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. , 2003, Current medicinal chemistry.

[49]  B. Derrida.  Random-energy model: An exactly solvable model of disordered systems , 1981 .

[50]  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).

[51]  F. G. Ball,et al.  Stochastic models for ion channels: introduction and bibliography. , 1992, Mathematical biosciences.

[52]  A. Halestrap,et al.  The permeability transition pore complex: another view. , 2002, Biochimie.

[53]  J. Hopfield,et al.  CO binding to heme proteins: A model for barrier height distributions and slow conformational changes , 1983 .

[54]  R. Hoffman,et al.  Depth-targeted efficient gene delivery and expression in the skin by pulsed electric fields: an approach to gene therapy of skin aging and other diseases. , 1996, Biochemical and biophysical research communications.

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

[56]  S. Snyder,et al.  Monoclonal antibody production by receptor-mediated electrically induced cell fusion , 1984, Nature.

[57]  W. Hamilton,et al.  Effects of high electric fields on micro-organisms. 3. Lysis of erythrocytes and protoplasts. , 1968, Biochimica et biophysica acta.

[58]  John C Reed,et al.  A method for functional evaluation of caspase activation pathways in intact lymphoid cells using electroporation-mediated protein delivery and flow cytometric analysis. , 2003, Journal of immunological methods.

[59]  Full band Monte Carlo study of high field transport in cubic phase silicon carbide , 2003 .

[60]  H. Kramers.  Brownian motion in a field of force and the diffusion model of chemical reactions , 1940 .

[61]  A Irimajiri,et al.  Dielectric analysis of mitochondria isolated from rat liver. II. Intact mitochondria as simulated by a double-shell model. , 1984, Biochimica et biophysica acta.

[62]  F Elinder,et al.  Modelling the activation, opening, inactivation and reopening of the voltage–gated sodium channel , 1998, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[63]  Guido Kroemer,et al.  Mitochondrial control of cell death , 2000, Nature Medicine.

[64]  P. Champion,et al.  Resonance Raman investigations of cytochrome c conformational change upon interaction with the membranes of intact and Ca2+-exposed mitochondria. , 2003, Biochemistry.