Electroporating fields target oxidatively damaged areas in the cell membrane.
Reversible electropermeabilization (electroporation) is widely used to facilitate the introduction of genetic material and pharmaceutical agents into living cells. Although considerable knowledge has been gained from the study of real and simulated model membranes in electric fields, efforts to optimize electroporation protocols are limited by a lack of detailed understanding of the molecular basis for the electropermeabilization of the complex biomolecular assembly that forms the plasma membrane. We show here, with results from both molecular dynamics simulations and experiments with living cells, that the oxidation of membrane components enhances the susceptibility of the membrane to electropermeabilization. Manipulation of the level of oxidative stress in cell suspensions and in tissues may lead to more efficient permeabilization procedures in the laboratory and in clinical applications such as electrochemotherapy and electrotransfection-mediated gene therapy.
Vernier
P Thomas
PT
Ming Hsieh Department of Electrical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, United States of America. vernier@mosis.com
Levine
Zachary A
ZA
Wu
Yu-Hsuan
YH
Joubert
Vanessa
V
Ziegler
Matthew J
MJ
Mir
Lluis M
LM
Tieleman
D Peter
DP
D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D003198:Computer Simulation; D053672:Electrochemotherapy / Q000379:methods; D018274:Electroporation / Q000379:methods*; D005583:Fourier Analysis; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D019169:Jurkat Cells; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008856:Microscopy, Fluorescence / Q000379:methods; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry
D008051:Lipid Bilayers; D008055:Lipids; D010713:Phosphatidylcholines; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; D010100:Oxygen