Cholesterol under oxidative stress: How lipid membranes sense oxidation as cholesterol is being replaced by oxysterols

Waldemar Kulig, Agnieszka Olzyńska, Piotr Jurkiewicz, Anu M. Kantola, Sanna Komulainen, Moutusi Manna, Mohsen Pourmousa, Mario Vazdar, Lukasz Cwiklik, Tomasz Rog, George Khelashvili, Daniel Harries, Ville Veikko Telkki, Martin Hof, Ilpo Vattulainen, Pavel Jungwirth

    Research output: Contribution to journalArticleScientificpeer-review

    34 Citations (Scopus)

    Abstract

    The behavior of oxysterols in phospholipid membranes and their effects on membrane properties were investigated by means of dynamic light scattering, fluorescence spectroscopy, NMR, and extensive atomistic simulations. Two families of oxysterols were scrutinized - tail-oxidized sterols, which are mostly produced by enzymatic processes, and ring-oxidized sterols, formed mostly via reactions with free radicals. The former family of sterols was found to behave similar to cholesterol in terms of molecular orientation, roughly parallel to the bilayer normal, leading to increasing membrane stiffness and suppression of its membrane permeability. In contrast, ring-oxidized sterols behave quantitatively differently from cholesterol. They acquire tilted orientations and therefore disrupt the bilayer structure with potential implications for signaling and other biochemical processes in the membranes.

    Original languageEnglish
    Pages (from-to)30-41
    Number of pages12
    JournalFree Radical Biology and Medicine
    Volume84
    DOIs
    Publication statusPublished - 1 Jul 2015
    Publication typeA1 Journal article-refereed

    Keywords

    • Phospholipid bilayers
    • Oxysterols
    • Molecular dynamics simulations
    • DPH anisotropy
    • NMR measurements
    • Laurdan fluorescence
    • Liposomes
    • Tilt modulus
    • FLUORESCENCE SOLVENT RELAXATION
    • MOLECULAR-DYNAMICS METHOD
    • MODEL MEMBRANES
    • FOURIER TRANSFORMATION
    • POTENTIAL FUNCTIONS
    • SOLVATION DYNAMICS
    • BENDING RIGIDITY
    • ORDER PARAMETERS
    • BILAYERS
    • PROTEINS

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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