Tail-Oxidized Cholesterol Enhances Membrane Permeability for Small Solutes

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Olzynska , A , Kulig , W , Mikkolainen , H , Czerniak , T , Jurkiewicz , P , Cwiklik , L , Rog , T , Hof , M , Jungwirth , P & Vattulainen , I 2020 , ' Tail-Oxidized Cholesterol Enhances Membrane Permeability for Small Solutes ' , Langmuir , vol. 36 , no. 35 , pp. 10438-10447 . https://doi.org/10.1021/acs.langmuir.0c01590

Title: Tail-Oxidized Cholesterol Enhances Membrane Permeability for Small Solutes
Author: Olzynska, Agnieszka; Kulig, Waldemar; Mikkolainen, Heikki; Czerniak, Tomasz; Jurkiewicz, Piotr; Cwiklik, Lukasz; Rog, Tomasz; Hof, Martin; Jungwirth, Pavel; Vattulainen, Ilpo
Other contributor: University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
University of Helsinki, Department of Physics
Date: 2020-09-08
Language: eng
Number of pages: 10
Belongs to series: Langmuir
ISSN: 0743-7463
DOI: https://doi.org/10.1021/acs.langmuir.0c01590
URI: http://hdl.handle.net/10138/320186
Abstract: Cholesterol renders mammalian cell membranes more compact by reducing the amount of voids in the membrane structure. Because of this, cholesterol is known to regulate the ability of cell membranes to prevent the permeation of water and water-soluble molecules through the membranes. Meanwhile, it is also known that even seemingly tiny modifications in the chemical structure of cholesterol can lead to notable changes in membrane properties. The question is, how significantly do these small changes in cholesterol structure affect the permeability barrier function of cell membranes? In this work, we applied fluorescence methods as well as atomistic molecular dynamics simulations to characterize changes in lipid membrane permeability induced by cholesterol oxidation. The studied 7 beta-hydroxycholesterol (7 beta-OH-chol) and 27-hydroxycholesterol (27-OH-chol) represent two distinct groups of oxysterols, namely, ring- and tail-oxidized cholesterols, respectively. Our previous research showed that the oxidation of the cholesterol tail has only a marginal effect on the structure of a lipid bilayer; however, oxidation was found to disturb membrane dynamics by introducing a mechanism that allows sterol molecules to move rapidly back and forth across the membranebobbing. Herein, we show that bobbing of 27-OH-chol accelerates fluorescence quenching of NBD-lipid probes in the inner leaflet of liposomes by dithionite added to the liposomal suspension. Systematic experiments using fluorescence quenching spectroscopy and microscopy led to the conclusion that the presence of 27-OH-chol increases membrane permeability to the dithionite anion. Atomistic molecular dynamics simulations demonstrated that 27-OH-chol also facilitates water transport across the membrane. The results support the view that oxysterol bobbing gives rise to successive perturbations to the hydrophobic core of the membrane, and these perturbations promote the permeation of water and small water-soluble molecules through a lipid bilayer. The observed impairment of permeability can have important consequences for eukaryotic organisms. The effects described for 27-OH-chol were not observed for 7 beta-OH-chol which represents ring-oxidized sterols.
Subject: MOLECULAR-DYNAMICS SIMULATIONS
ALKYL CHAIN UNSATURATION
ATOM FORCE-FIELD
LIPID-BILAYER
PHOSPHOLIPIDS
LIPOSOMES
OXIDATION
TRANSLOCATION
TRANSITIONS
OXYSTEROLS
114 Physical sciences
1182 Biochemistry, cell and molecular biology
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