title: Cell membrane permeabilization by 12-ns electric pulses: Not a purely dielectric, but a charge-dependent phenomenon.
abstract: Electric pulses of a few nanoseconds in duration can induce reversible permeabilization of cell membrane and cell death. Whether these effects are caused by ionic or purely dielectric phenomena is still discussed. We address this question by studying the impact of conductivity of the pulsing buffer on the effect of pulses of 12 ns and 3.2 MV/m on the DC-3F mammalian cell line. When pulses were applied in a high-conductivity medium (1.5 S/m), cells experienced both reversible electropermeabilization and cell death. On the contrary, no effect was observed in the low-conductivity medium (0.1 S/m). Possible artifacts due to differences in viscosity, temperature increase or electrochemical reactions were excluded. The influence of conductivity reported here suggests that charges still play a role, even for 12-ns pulses. All theoretical models agree with this experimental observation, since all suggest that only high-conductivity medium can induce a transmembrane voltage high enough to induce pore creation, in turn. However, most models fail to describe why pulse accumulation is experimentally required to observe biological effects. They mostly show no increase of permeabilization with accumulation of pulses. Currently, only one model properly describes pulse accumulation by modeling diffusion of the altered membrane regions.
authors.affiliation: Institute for Pulsed Power and Microwave Technology, Karlsruhe Institute of Technology, Germany; CNRS, Villejuif, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France; Univ Paris-Sud, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France; Gustave Roussy, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France. Electronic address: aude.silve@kit.edu.
authors.forename: Aude
authors.initials: A
authors.lastname: Silve
authors.affiliation: CNRS, Villejuif, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France; Univ Paris-Sud, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France; Gustave Roussy, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leray
authors.affiliation: Inria Bordeaux, CNRS UMR 5251, Université de Bordeaux, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Leguèbe
authors.affiliation: Inria Bordeaux, CNRS UMR 5251, Université de Bordeaux, France.
authors.forename: Clair
authors.initials: C
authors.lastname: Poignard
authors.affiliation: CNRS, Villejuif, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France; Univ Paris-Sud, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France; Gustave Roussy, Laboratoire de Vectorologie et Thérapeutiques Anti-cancéreuses, UMR 8203, Villejuif 94805, France. Electronic address: luis.mir@gustaveroussy.fr.
authors.forename: Lluis M
authors.initials: LM
authors.lastname: Mir
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D002463:Cell Membrane Permeability; D003412:Cricetulus; D003470:Culture Media; D004058:Diffusion; D018274:Electroporation / Q000379:methods*; D008962:Models, Theoretical; D013696:Temperature; D014783:Viscosity
chemical_list: D003470:Culture Media
keywords: Electropermeabilization; Electroporation; Medium conductivity; Nanosecond-pulsed electric fields; Temperature