title: Magnification of Cholesterol-Induced Membrane Resistance on the Tissue Level: Implications for Hypoxia.
abstract: High cellular membrane cholesterol is known to generate membrane resistance and reduce oxygen (O2) permeability. As such, cholesterol may contribute to the Warburg effect in tumor cells by stimulating intracellular hypoxia that cannot be detected from extracellular oxygen measurements. We probe the tissue-level impact of the phenomenon, asking whether layering of cells can magnify the influence of cholesterol, to modulate hypoxia in relation to capillary proximity. Using molecular dynamics simulations, we affirm that minimally hydrated, adjacent lipid bilayers have independent physical behavior. Combining this insight with published experimental data, we predict linearly increasing impact of membrane cholesterol on oxygen flux across cells layered in tissue.
authors.affiliation: Department of Chemistry, New Mexico Institute of Mining and Technology (New Mexico Tech), 801 Leroy Place, Socorro, NM, 87801, USA.|Department of Mathematics, Chemistry, and Physics, West Texas A&M University, Canyon, TX, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Shea
authors.affiliation: Department of Chemistry, New Mexico Institute of Mining and Technology (New Mexico Tech), 801 Leroy Place, Socorro, NM, 87801, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Chemistry, New Mexico Institute of Mining and Technology (New Mexico Tech), 801 Leroy Place, Socorro, NM, 87801, USA. spias@nmt.edu.
authors.forename: Sally C
authors.initials: SC
authors.lastname: Pias
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D004058:Diffusion; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008567:Membranes, Artificial; D056004:Molecular Dynamics Simulation; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008563:Membrane Lipids; D008567:Membranes, Artificial; D002784:Cholesterol; D010100:Oxygen
keywords: Cancer; Cholesterol; Kinetics; Molecular dynamics simulation; Oxygen bioavailability