Water Bridges in Electropermeabilized Phospholipid Bilayers

Pulsed electric field permeabilization of living cell membranes forms the basis for widely used biotechnology protocols and an increasing number of therapeutic applications. Experimental observations of artificial membranes and whole cells and molecular and analytical models provide evidence that a membrane-spanning, hydrophilic, conductive pore can form in nanoseconds. An external electric field lowers the energy barrier for this stochastic process, reducing the mean time for pore formation and increasing the pore areal density. Molecular dynamic simulations reveal the key role played by interfacial water in electropermeabilization. These model systems, validated in the laboratory, are deepening our understanding of the factors governing pore initiation, construction, and lifetime, knowledge that will translate to enhanced utilization of this method in biomedicine and bioengineering.

[1]  P. Thomas Vernier,et al.  Cardiac myocyte excitation by ultrashort high-field pulses. , 2009, Biophysical journal.

[2]  M. R. Tarasevich,et al.  246 - Electric breakdown of bilayer lipid membranes I. The main experimental facts and their qualitative discussion , 1979 .

[3]  A. T. Esser,et al.  Membrane electroporation: The absolute rate equation and nanosecond time scale pore creation. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[4]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997, J. Comput. Chem..

[5]  O. Berger,et al.  Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. , 1997, Biophysical journal.

[6]  James C. Weaver,et al.  Electroporation of biological membranes from multicellular to nano scales , 2003 .

[7]  L. Chernomordik,et al.  Reversible electrical breakdown of lipid bilayers: formation and evolution of pores. , 1988, Biochimica et biophysica acta.

[8]  Martin A Gundersen,et al.  Nanosecond electric pulse-induced calcium entry into chromaffin cells. , 2008, Bioelectrochemistry.

[9]  W. Krassowska,et al.  Electroporation and Shock-Induced Transmembrane Potential in a Cardiac Fiber During Defibrillation Strength Shocks , 1998, Annals of Biomedical Engineering.

[10]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[11]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[12]  P. Kollman,et al.  Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models , 1992 .

[13]  Mark L. Zeidel,et al.  Structural Determinants of Water Permeability through the Lipid Membrane , 2008, The Journal of general physiology.

[14]  E. Neumann,et al.  Stochastic model for electric field-induced membrane pores. Electroporation. , 1984, Biophysical chemistry.

[15]  T. Darden,et al.  A smooth particle mesh Ewald method , 1995 .

[16]  W. Hamilton,et al.  Effects of high electric fields on microorganisms: II. Mechanism of action of the lethal effect , 1967 .

[17]  P. Vernier,et al.  Interface water dynamics and porating electric fields for phospholipid bilayers. , 2008, The journal of physical chemistry. B.

[18]  D. Popescu,et al.  A model for the appearance of statistical pores in membranes due to selfoscillations , 1991 .

[19]  Hidetoshi Matsumoto,et al.  Simulation study on the influence of an electric field on water evaporation , 2009 .

[20]  Alan E Mark,et al.  Simulation of pore formation in lipid bilayers by mechanical stress and electric fields. , 2003, Journal of the American Chemical Society.

[21]  H. Berendsen,et al.  Interaction Models for Water in Relation to Protein Hydration , 1981 .

[22]  Martin A Gundersen,et al.  Nanopore-facilitated, voltage-driven phosphatidylserine translocation in lipid bilayers—in cells and in silico , 2006, Physical biology.

[23]  Helmut Grubmüller,et al.  Kinetics, statistics, and energetics of lipid membrane electroporation studied by molecular dynamics simulations. , 2008, Biophysical journal.

[24]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[25]  D Peter Tieleman,et al.  BMC Biochemistry BioMed Central Research article The molecular basis of electroporation , 2004 .

[26]  I. Vattulainen,et al.  Pore formation coupled to ion transport through lipid membranes as induced by transmembrane ionic charge imbalance: atomistic molecular dynamics study. , 2005, Journal of the American Chemical Society.

[27]  Mounir Tarek,et al.  Membrane electroporation: a molecular dynamics simulation. , 2005, Biophysical journal.

[28]  Juergen F. Kolb,et al.  A new pulsed electric field therapy for melanoma disrupts the tumor's blood supply and causes complete remission without recurrence , 2009, International journal of cancer.

[29]  T. Straatsma,et al.  THE MISSING TERM IN EFFECTIVE PAIR POTENTIALS , 1987 .

[30]  M J Jaroszeski,et al.  Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy , 1996, Cancer.

[31]  Marie-Pierre Rols,et al.  Electropermeabilization, a physical method for the delivery of therapeutic molecules into cells. , 2006, Biochimica et biophysica acta.

[32]  A. Kuthi,et al.  A linear, single-stage, nanosecond pulse generator for delivering intense electric fields to biological loads , 2009, IEEE Transactions on Dielectrics and Electrical Insulation.

[33]  F. Andre,et al.  Gadolinium blocks membrane permeabilization induced by nanosecond electric pulses and reduces cell death. , 2010, Bioelectrochemistry.

[34]  Boris Rubinsky,et al.  Irreversible Electroporation in Medicine , 2007, Technology in cancer research & treatment.

[35]  R. Clarke.  The dipole potential of phospholipid membranes and methods for its detection. , 2001, Advances in colloid and interface science.

[36]  Bennett L Ibey,et al.  Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane. , 2009, Biochemical and biophysical research communications.

[37]  P. Thomas Vernier,et al.  Life Cycle of an Electropore: Field-Dependent and Field-Independent Steps in Pore Creation and Annihilation , 2010, The Journal of Membrane Biology.

[38]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997 .

[39]  K. Schoenbach,et al.  Simulations of transient membrane behavior in cells subjected to a high-intensity ultrashort electric pulse. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[40]  Martin A Gundersen,et al.  Nanoelectropulse-driven membrane perturbation and small molecule permeabilization , 2006, BMC Cell Biology.

[41]  Damijan Miklavčič,et al.  Electrochemotherapy – An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study , 2006 .

[42]  Frank Telang,et al.  Effects of cell phone radiofrequency signal exposure on brain glucose metabolism. , 2011, JAMA.

[43]  R. Benz,et al.  Pulse-length dependence of the electrical breakdown in lipid bilayer membranes. , 1980, Biochimica et biophysica acta.

[44]  J. Weaver,et al.  Theory of electroporation of planar bilayer membranes: predictions of the aqueous area, change in capacitance, and pore-pore separation. , 1994, Biophysical journal.

[45]  M. Rols,et al.  Mechanisms of cell membrane electropermeabilization: a minireview of our present (lack of ?) knowledge. , 2005, Biochimica et biophysica acta.

[46]  Shu Xiao,et al.  Manipulation of cell volume and membrane pore comparison following single cell permeabilization with 60- and 600-ns electric pulses. , 2011, Biochimica et biophysica acta.

[47]  Martin A Gundersen,et al.  Nanopore formation and phosphatidylserine externalization in a phospholipid bilayer at high transmembrane potential. , 2006, Journal of the American Chemical Society.

[48]  Ulrich Zimmermann,et al.  Dielectric Breakdown of Cell Membranes , 1974 .

[49]  P. Vernier,et al.  Nanosecond field alignment of head group and water dipoles in electroporating phospholipid bilayers. , 2007, The journal of physical chemistry. B.

[50]  R. Stämpfli,et al.  Membrane potential of a ranvier node measured after electrical destruction of its membrane , 1957, Experientia.

[51]  Y. Chizmadzhev,et al.  Bilayer lipid membranes in strong electric fields , 1980 .

[52]  Laura Marcu,et al.  In vitro and in vivo evaluation and a case report of intense nanosecond pulsed electric field as a local therapy for human malignancies , 2007, International journal of cancer.

[53]  Wanda Krassowska,et al.  Asymptotic model of electroporation , 1999 .

[54]  H. Coster,et al.  A quantitative analysis of the voltage-current relationships of fixed charge membranes and the associated property of "punch-through". , 1965, Biophysical journal.

[55]  P. A. Mason,et al.  Radiofrequency-Radiation Exposure Does Not Induce Detectable Leakage of Albumin Across the Blood-Brain Barrier , 2009, Radiation research.

[56]  J. Weaver,et al.  Theory of electroporation: A review , 1996 .

[57]  U. Zimmermann,et al.  Electric field-mediated fusion and related electrical phenomena. , 1982, Biochimica et biophysica acta.

[58]  M. Berkowitz,et al.  Molecular model of a cell plasma membrane with an asymmetric multicomponent composition: water permeation and ion effects. , 2009, Biophysical journal.

[59]  E. Neumann,et al.  Gene transfer into mouse lyoma cells by electroporation in high electric fields. , 1982, The EMBO journal.