Ultrashort electrical pulses open a new gateway into biological cells

An electrical model for biological cells predicts that for pulses with durations shorter than the charging time of the outer membrane, there is an increasing probability of electric field interactions with intracellular structures. Experimental studies in which human cells were exposed to pulsed electric fields of up to 300-kV/cm amplitude, with durations as short as 10 ns, have confirmed this hypothesis. The observed effects include the breaching of intracellular granule membranes without permanent damage to the cell membrane, abrupt rises in intracellular free calcium levels, and enhanced expression of genes. At increased electric fields, the application of submicrosecond pulses induces apoptosis (programmed cell death) in biological cells, an effect that has been shown to reduce the growth of tumors. Possible applications of the intracellular electroeffect are enhancing gene delivery to the nucleus, controlling cell functions that depend on calcium release (causing cell immobilization), and treating tumors.

[1]  Henry H. Mantsch,et al.  Vibrational spectroscopy and medicine: an alliance in the making , 2002 .

[2]  Charles Polk,et al.  CRC Handbook of Biological Effects of Electromagnetic Fields , 1986 .

[3]  Fabio Di Lisa,et al.  PUVA‐induced apoptosis involves mitochondrial dysfunction caused by the opening of the permeability transition pore , 2002, FEBS letters.

[4]  Laura Marcu,et al.  Calcium bursts induced by nanosecond electric pulses. , 2003, Biochemical and biophysical research communications.

[5]  K. H. Schoenbach,et al.  Effects of submicrosecond, high intensity pulsed electric fields on living cells - intracellular electromanipulation , 2003 .

[6]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[7]  E. Fontaine,et al.  Progress on the Mitochondrial Permeability Transition Pore: Regulation by Complex I and Ubiquinone Analogs , 1999, Journal of bioenergetics and biomembranes.

[8]  WU KarenT,et al.  Results , 1969 .

[9]  Kenneth S. Cole.  Electric impedance of marine egg membranes , 1937 .

[10]  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).

[11]  Juergen F Kolb,et al.  Nanosecond pulsed electric field generators for the study of subcellular effects , 2006, Bioelectromagnetics.

[12]  K. Schoenbach,et al.  Differential effects in cells exposed to ultra-short, high intensity electric fields: cell survival, DNA damage, and cell cycle analysis. , 2003, Mutation research.

[13]  J C Ameisen.  [The origin of programmed cell death in the flow of evolution and its role in host-pathogen interactions]. , 1998, Comptes rendus des seances de la Societe de biologie et de ses filiales.

[14]  K. Schoenbach,et al.  Sub-microsecond, intense pulsed electric field applications to cells show specificity of effects. , 2003, Bioelectrochemistry.

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

[16]  K. Schoenbach,et al.  Self-consistent simulations of electroporation dynamics in biological cells subjected to ultrashort electrical pulses. , 2001, Physical review. E, Statistical, nonlinear, and soft matter physics.

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

[18]  K. Schoenbach,et al.  Electroporation dynamics in biological cells subjected to ultrafast electrical pulses: a numerical simulation study. , 2000, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[19]  L. Hartwell,et al.  Cell cycle control and cancer. , 1994, Science.

[20]  Laura Marcu,et al.  Pulse generators for pulsed electric field exposure of biological cells and tissues , 2003 .

[21]  E. Neumann,et al.  Electroporative deformation of salt filled lipid vesicles , 1998, European Biophysics Journal.

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

[23]  E. Neumann,et al.  Conductometric and electrooptic relaxation spectrometry of lipid vesicle electroporation at high fields , 2002 .

[24]  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.

[25]  Laura Marcu,et al.  Ultrashort pulsed electric fields induce membrane phospholipid translocation and caspase activation: differential sensitivities of Jurkat T lymphoblasts and rat glioma C6 cells , 2003 .

[26]  Werner R. Loewenstein,et al.  Some Electrical Properties of a Nuclear Membrane Examined with a Microelectrode , 1963, The Journal of general physiology.

[27]  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.

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

[29]  Yuri Feldman,et al.  Time domain dielectric spectroscopy study of biological systems , 2003 .

[30]  K. Schoenbach,et al.  Diverse effects of nanosecond pulsed electric fields on cells and tissues. , 2003, DNA and cell biology.

[31]  Juergen F Kolb,et al.  Leukemic cell intracellular responses to nanosecond electric fields. , 2004, Biochemical and biophysical research communications.

[32]  H. P. Schwan,et al.  Interactions between Electromagnetic Fields. , 1985 .

[33]  H. Itoh,et al.  Time courses of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. , 1993, Biophysical journal.

[34]  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.

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

[36]  E. Neumann,et al.  The Relaxation Hysteresis of Membrane Electroporation , 1989 .

[37]  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.

[38]  E. Neumann,et al.  Electroporation and Electrofusion in Cell Biology , 1989, Springer US.

[39]  Tao Cheng,et al.  Pulsed electric fields for selection of hematopoietic cells and depletion of tumor cell contaminants , 2000, Nature Biotechnology.

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

[41]  K. H. Schoenbach,et al.  Biofouling prevention with pulsed electric fields , 2000 .

[42]  Michael R. Murphy,et al.  Low-intensity millimeter waves as a novel therapeutic modality , 1999 .

[43]  Ulrich Zimmermann,et al.  Electromanipulation of cells , 1996 .

[44]  R. Pethig,et al.  Applications of dielectrophoresis in biotechnology. , 1997, Trends in biotechnology.

[45]  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).

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

[47]  James C Weaver,et al.  An approach to electrical modeling of single and multiple cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[48]  H. P. Schwan,et al.  Interactions between electromagnetic fields and cells , 1985 .

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