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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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 languageAmerican English
Pages (from-to)30-41
Number of pages12
JournalFree Radical Biology and Medicine
Volume84
DOIs
StatePublished - 1 Jul 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.All rights reserved.

Keywords

  • DPH anisotropy
  • Laurdan fluorescence
  • Liposomes
  • Molecular dynamics simulations
  • NMR measurements
  • Oxysterols
  • Phospholipid bilayers
  • Tilt modulus

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