title: Quantification of cell membrane permeability induced by monopolar and high-frequency bipolar bursts of electrical pulses.
abstract: High-frequency bipolar electric pulses have been shown to mitigate undesirable muscle contraction during irreversible electroporation (IRE) therapy. Here, we evaluate the potential applicability of such pulses for introducing exogenous molecules into cells, such as in electrochemotherapy (ECT). For this purpose we develop a method for calculating the time course of the effective permeability of an electroporated cell membrane based on real-time imaging of propidium transport into single cells that allows a quantitative comparison between different pulsing schemes. We calculate the effective permeability for several pulsed electric field treatments including trains of 100μs monopolar pulses, conventionally used in IRE and ECT, and pulse trains containing bursts or evenly-spaced 1μs bipolar pulses. We show that shorter bipolar pulses induce lower effective membrane permeability than longer monopolar pulses with equivalent treatment times. This lower efficiency can be attributed to incomplete membrane charging. Nevertheless, bipolar pulses could be used for increasing the uptake of small molecules into cells more symmetrically, but at the expense of higher applied voltages. These data indicate that high-frequency bipolar bursts of electrical pulses may be designed to electroporate cells as effectively as and more homogeneously than conventional monopolar pulses.
authors.affiliation: Virginia Tech, Department of Biomedical Engineering and Mechanics, 330 Kelly Hall, Blacksburg, USA. Electronic address: sweeneyd@vt.edu.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Sweeney
authors.affiliation: University of Ljubljana, Faculty of Electrical Engineering, Tržaška 25, SI 1000, Ljubljana, Slovenia. Electronic address: matej.rebersek@fe.uni-lj.si.
authors.forename: Matej
authors.initials: M
authors.lastname: Reberšek
authors.affiliation: University of Ljubljana, Faculty of Electrical Engineering, Tržaška 25, SI 1000, Ljubljana, Slovenia. Electronic address: janja.dermol@fe.uni-lj.si.
authors.forename: Janja
authors.initials: J
authors.lastname: Dermol
authors.affiliation: University of Ljubljana, Faculty of Electrical Engineering, Tržaška 25, SI 1000, Ljubljana, Slovenia. Electronic address: lea.rems@fe.uni-lj.si.
authors.forename: Lea
authors.initials: L
authors.lastname: Rems
authors.affiliation: University of Ljubljana, Faculty of Electrical Engineering, Tržaška 25, SI 1000, Ljubljana, Slovenia. Electronic address: damijan.miklavcic@fe.uni-lj.si.
authors.forename: Damijan
authors.initials: D
authors.lastname: Miklavčič
authors.affiliation: Virginia Tech, Department of Biomedical Engineering and Mechanics, 330 Kelly Hall, Blacksburg, USA. Electronic address: davalos@vt.edu.
authors.forename: Rafael V
authors.initials: RV
authors.lastname: Davalos
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003412:Cricetulus; D004566:Electrodes; D018274:Electroporation / Q000379:methods*; D008564:Membrane Potentials / Q000502:physiology; D011419:Propidium / Q000378:metabolism*; D059010:Single-Cell Analysis / Q000295:instrumentation / Q000379:methods*
chemical_list: D011419:Propidium
keywords: Bipolar electrical pulses; Electrochemotherapy; Electroporation; Gene electrotransfer; Irreversible electroporation; Permeability