title: Synergistic effect of electric field and lipid oxidation on the permeability of cell membranes.
abstract: Strong electric fields are known to affect cell membrane permeability, which can be applied for therapeutic purposes, e.g., in cancer therapy. A synergistic enhancement of this effect may be accomplished by the presence of reactive oxygen species (ROS), as generated in cold atmospheric plasmas. Little is known about the synergy between lipid oxidation by ROS and the electric field, nor on how this affects the cell membrane permeability.
  
  
  
  We here conduct molecular dynamics simulations to elucidate the dynamics of the permeation process under the influence of combined lipid oxidation and electroporation. A phospholipid bilayer (PLB), consisting of di-oleoyl-phosphatidylcholine molecules covered with water layers, is used as a model system for the plasma membrane.
  
  
  
  We show how oxidation of the lipids in the PLB leads to an increase of the permeability of the bilayer to ROS, although the permeation free energy barriers still remain relatively high. More importantly, oxidation of the lipids results in a drop of the electric field threshold needed for pore formation (i.e., electroporation) in the PLB. The created pores in the membrane facilitate the penetration of reactive plasma species deep into the cell interior, eventually causing oxidative damage.
  
  
  
  This study is of particular interest for plasma medicine, as plasma generates both ROS and electric fields, but it is also of more general interest for applications where strong electric fields and ROS both come into play.
authors.affiliation: Research Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. Electronic address: maksudbek.yusupov@uantwerpen.be.
authors.forename: M
authors.initials: M
authors.lastname: Yusupov
authors.affiliation: Research Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van der Paal
authors.affiliation: Research Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: E C
authors.initials: EC
authors.lastname: Neyts
authors.affiliation: Research Group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Bogaerts
mesh_terms: D002462:Cell Membrane / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D004560:Electricity; D018274:Electroporation / Q000379:methods; D008051:Lipid Bilayers / Q000378:metabolism*; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D017382:Reactive Oxygen Species; D014867:Water
keywords: Cell membrane; Electric field; Electroporation; Molecular dynamics simulation; Plasma medicine; Reactive oxygen species