title: Direct Measurement of the Effect of Cholesterol and 6-Ketocholestanol on the Membrane Dipole Electric Field Using Vibrational Stark Effect Spectroscopy Coupled with Molecular Dynamics Simulations.
abstract: Biological membranes are heterogeneous structures with complex electrostatic profiles arising from lipids, sterols, membrane proteins, and water molecules. We investigated the effect of cholesterol and its derivative 6-ketocholestanol (6-kc) on membrane electrostatics by directly measuring the dipole electric field (F⃗d) within lipid bilayers containing cholesterol or 6-kc at concentrations of 0-40 mol% through the vibrational Stark effect (VSE). We found that adding low concentrations of cholesterol, up to ∼10 mol %, increases F⃗d, while adding more cholesterol up to 40 mol% lowers F⃗d. In contrast, we measured a monotonic increase in F⃗das 6-kc concentration increased. We propose that this membrane electric field is affected by multiple factors: the polarity of the sterol molecules, the reorientation of the phospholipid dipole due to sterol, and the impact of the sterol on hydrogen bonding with surface water. We used molecular dynamics simulations to examine the distribution of phospholipids, sterol, and helix in bilayers containing these sterols. At low concentrations, we observed clustering of sterols near the vibrational probe whereas at high concentrations, we observed spatial correlation between the positions of the sterol molecules. This work demonstrates how a one-atom difference in a sterol changes the physicochemical and electric field properties of the bilayer.
authors.affiliation: Department of Chemistry, ‡Institute for Cell and Molecular Biology, §Center for Nano- and Molecular Science and Technology, and ∥Institute for Computational Engineering and Sciences, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Rebika
authors.initials: R
authors.lastname: Shrestha
authors.affiliation: Department of Chemistry, ‡Institute for Cell and Molecular Biology, §Center for Nano- and Molecular Science and Technology, and ∥Institute for Computational Engineering and Sciences, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Cari M
authors.initials: CM
authors.lastname: Anderson
authors.affiliation: Department of Chemistry, ‡Institute for Cell and Molecular Biology, §Center for Nano- and Molecular Science and Technology, and ∥Institute for Computational Engineering and Sciences, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Alfredo E
authors.initials: AE
authors.lastname: Cardenas
authors.affiliation: Department of Chemistry, ‡Institute for Cell and Molecular Biology, §Center for Nano- and Molecular Science and Technology, and ∥Institute for Computational Engineering and Sciences, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Ron
authors.identifier: 0000-0001-7849-415X
authors.initials: R
authors.lastname: Elber
authors.affiliation: Department of Chemistry, ‡Institute for Cell and Molecular Biology, §Center for Nano- and Molecular Science and Technology, and ∥Institute for Computational Engineering and Sciences, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Lauren J
authors.identifier: 0000-0001-9999-5500
authors.initials: LJ
authors.lastname: Webb
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D004574:Electromagnetic Fields; D007653:Ketocholesterols / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D013055:Spectrophotometry, Infrared; D055672:Static Electricity; D013499:Surface Properties; D014732:Vibration; D014867:Water / Q000737:chemistry
chemical_list: D007653:Ketocholesterols; D008051:Lipid Bilayers; D014867:Water; C063833:6-ketocholestanol; D002784:Cholesterol