A Silve1, A Guimerà Brunet2, B Al-Sakere3, A Ivorra4, L M Mir5. 1. Univ Paris-Sud, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, Villejuif F-94805, France; CNRS, Villejuif, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, F-94805, France; Gustave Roussy, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, Villejuif F-94805, France; Karlsruhe Institute of Technology (KIT), Institute for Pulsed Power and Microwave Technology (IHM), 76344 Eggenstein-Leopoldshafen, Germany. Electronic address: aude.silve@gmail.com. 2. Institut de Microelectrònica de Barcelona IMB-CNM (CSIC), Bellaterra, 08193 Barcelona, Spain; CIBER-BBN, Networking Center on Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain. 3. Univ Paris-Sud, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, Villejuif F-94805, France; CNRS, Villejuif, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, F-94805, France; Gustave Roussy, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, Villejuif F-94805, France. 4. Universitat Pompeu Fabra, Departament de Tecnologies de la Informació i les Comunicacions, Carrer Roc Boronat 138, E-08018 Barcelona, Spain. 5. Univ Paris-Sud, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, Villejuif F-94805, France; CNRS, Villejuif, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, F-94805, France; Gustave Roussy, Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, UMR 8203, Villejuif F-94805, France. Electronic address: luismir@igr.fr.
Abstract
BACKGROUND: Applications of cell electropermeabilization are rapidly growing but basic concepts are still unclear. In particular, the impact of electric pulse repetition rate in the efficiency of permeabilization has not yet been understood. METHODS: The impact of electric pulse repetition rate in the efficiency of permeabilization was analyzed in experiments performed on potato tissue and partially transposed on mice liver. On potato tissue, pulses with durations of 100μs or 10ns are applied. The intensity of permeabilization was quantified by means of bioimpedance changes and electric current measurements and a new index was defined. RESULTS: For the two pulse durations tested, very low repetition rates (below 0.1Hz) are much more efficient to achieve cell permeabilization in potato tissue. In mice liver, using 100μs pulses, the influence of the repetition rate is more complex. Indeed, repetition rates of 1Hz and 10Hz are more efficient than 100Hz or 1kHz, but not the repetition rate of 0.1Hz for which there is an impact of the living mice organism response. CONCLUSIONS: We propose that the effects reported here might be caused by an electroporation-induced cell membrane 'electro-desensitization' which requires seconds to dissipate due to membrane resealing. GENERAL SIGNIFICANCE: This study not only reinforces previous observations, but moreover it sustains a new concept of 'electro-desensitization' which is the first unifying mechanism enabling to explain all the results obtained until now both in vitro and in vivo, with long and short pulses.
BACKGROUND: Applications of cell electropermeabilization are rapidly growing but basic concepts are still unclear. In particular, the impact of electric pulse repetition rate in the efficiency of permeabilization has not yet been understood. METHODS: The impact of electric pulse repetition rate in the efficiency of permeabilization was analyzed in experiments performed on potato tissue and partially transposed on mice liver. On potato tissue, pulses with durations of 100μs or 10ns are applied. The intensity of permeabilization was quantified by means of bioimpedance changes and electric current measurements and a new index was defined. RESULTS: For the two pulse durations tested, very low repetition rates (below 0.1Hz) are much more efficient to achieve cell permeabilization in potato tissue. In mice liver, using 100μs pulses, the influence of the repetition rate is more complex. Indeed, repetition rates of 1Hz and 10Hz are more efficient than 100Hz or 1kHz, but not the repetition rate of 0.1Hz for which there is an impact of the living mice organism response. CONCLUSIONS: We propose that the effects reported here might be caused by an electroporation-induced cell membrane 'electro-desensitization' which requires seconds to dissipate due to membrane resealing. GENERAL SIGNIFICANCE: This study not only reinforces previous observations, but moreover it sustains a new concept of 'electro-desensitization' which is the first unifying mechanism enabling to explain all the results obtained until now both in vitro and in vivo, with long and short pulses.
Authors: Sarah D Jensen; Vera A Khorokhorina; Claudia Muratori; Andrei G Pakhomov; Olga N Pakhomova Journal: Sci Rep Date: 2017-09-08 Impact factor: 4.379