Electric Field-Driven Water Dipoles: Nanoscale Architecture of Electroporation

Tokman, Mayya; Lee, Jane HyoJin; Levine, Zachary A.; Ho, Ming-Chak; Colvin, Michael E.; Vernier, P. Thomas

doi:10.1371/journal.pone.0061111

Electric Field-Driven Water Dipoles: Nanoscale Architecture of Electroporation

Journal Article · Thu Apr 11 00:00:00 EDT 2013 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0061111· OSTI ID:1904674

Tokman, Mayya ^[1]; Lee, Jane HyoJin ^[2]; Levine, Zachary A. ^[3]; Ho, Ming-Chak ^[3]; Colvin, Michael E. ^[2]; Vernier, P. Thomas ^[3]

University of California, Merced, CA (United States); Univ. of California, Merced, CA (United States)
University of California, Merced, CA (United States)
University of Southern California, Los Angeles, CA (United States)

Electroporation is the formation of permeabilizing structures in the cell membrane under the influence of an externally imposed electric field. The resulting increased permeability of the membrane enables a wide range of biological applications, including the delivery of normally excluded substances into cells. While electroporation is used extensively in biology, biotechnology, and medicine, its molecular mechanism is not well understood. This lack of knowledge limits the ability to control and fine-tune the process. In this article we propose a novel molecular mechanism for the electroporation of a lipid bilayer based on energetics analysis. Using molecular dynamics simulations we demonstrate that pore formation is driven by the reorganization of the interfacial water molecules. Our energetics analysis and comparisons of simulations with and without the lipid bilayer show that the process of poration is driven by field-induced reorganization of water dipoles at the water-lipid or water-vacuum interfaces into more energetically favorable configurations, with their molecular dipoles oriented in the external field. Although the contributing role of water in electroporation has been noted previously, here we propose that interfacial water molecules are the main players in the process, its initiators and drivers. The role of the lipid layer, to a first-order approximation, is then reduced to a relatively passive barrier. This new view of electroporation simplifies the study of the problem, and opens up new opportunities in both theoretical modeling of the process and experimental research to better control or to use it in new, innovative ways.

View Accepted Manuscript (DOE)

Research Organization:: University of California, Merced, CA (United States); University of Southern California, Los Angeles, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR)

Grant/Contract Number:: FG02-04ER25625

OSTI ID:: 1904674

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 4 Vol. 8; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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