title: Hampering Effect of Cholesterol on the Permeation of Reactive Oxygen Species through Phospholipids Bilayer: Possible Explanation for Plasma Cancer Selectivity.
abstract: In recent years, the ability of cold atmospheric pressure plasmas (CAPS) to selectively induce cell death in cancer cells has been widely established. This selectivity has been assigned to the reactive oxygen and nitrogen species (RONS) created in CAPs. To provide new insights in the search for an explanation for the observed selectivity, we calculate the transfer free energy of multiple ROS across membranes containing a varying amount of cholesterol. The cholesterol fraction is investigated as a selectivity parameter because membranes of cancer cells are known to contain lower fractions of cholesterol compared to healthy cells. We find that cholesterol has a significant effect on the permeation of reactive species across a membrane. Indeed, depending on the specific reactive species, an increasing cholesterol fraction can lead to (i) an increase of the transfer free energy barrier height and width, (ii) the formation of a local free energy minimum in the center of the membrane and (iii) the creation of extra free energy barriers due to the bulky sterol rings. In the context of plasma oncology, these observations suggest that the increased ingress of RONS in cancer cells can be explained by the decreased cholesterol fraction of their cell membrane.
authors.affiliation: Research group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk-Antwerp, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Van der Paal
authors.affiliation: Research group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk-Antwerp, Belgium.
authors.forename: Claudia
authors.initials: C
authors.lastname: Verheyen
authors.affiliation: Research group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk-Antwerp, Belgium.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Neyts
authors.affiliation: Research group PLASMANT, Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk-Antwerp, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Bogaerts
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D002784:Cholesterol