Cholesterol Stiffening of Lipid Membranes

Fathima T. Doole, Teshani Kumarage, Rana Ashkar, Michael F. Brown

Research output: Contribution to journalReview articlepeer-review

Abstract

Biomembrane order, dynamics, and other essential physicochemical parameters are controlled by cholesterol, a major component of mammalian cell membranes. Although cholesterol is well known to exhibit a condensing effect on fluid lipid membranes, the extent of stiffening that occurs with different degrees of lipid acyl chain unsaturation remains an enigma. In this review, we show that cholesterol locally increases the bending rigidity of both unsaturated and saturated lipid membranes, suggesting there may be a length-scale dependence of the bending modulus. We review our published data that address the origin of the mechanical effects of cholesterol on unsaturated and polyunsaturated lipid membranes and their role in biomembrane functions. Through a combination of solid-state deuterium NMR spectroscopy and neutron spin-echo spectroscopy, we show that changes in molecular packing cause the universal effects of cholesterol on the membrane bending rigidity. Our findings have broad implications for the role of cholesterol in lipid–protein interactions as well as raft-like mixtures, drug delivery applications, and the effects of antimicrobial peptides on lipid membranes. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)385-405
Number of pages21
JournalJournal of Membrane Biology
Volume255
Issue number4-5
DOIs
StatePublished - Oct 2022

Keywords

  • Area per lipid
  • Cholesterol
  • Membrane elasticity
  • Neutron spin-echo
  • Rafts
  • Solid-state NMR spectroscopy

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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