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Cholesterol-induced fluid-phase immiscibility in membranes.

M B Sankaram1, T E Thompson

  • 1Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville 22908.

Proceedings of the National Academy of Sciences of the United States of America
|October 1, 1991
PubMed
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Cholesterol and phospholipid mixtures form two fluid phases. Magnetic resonance reveals cholesterol spans the bilayer in one phase and distributes across both in the other, suggesting a hydrogen bond interaction.

Area of Science:

  • Biophysics
  • Materials Science
  • Physical Chemistry

Background:

  • Cholesterol is a key component of biological membranes, influencing their fluidity and structure.
  • Phosphatidylcholines are major phospholipids in cell membranes.
  • Understanding lipid-raft formation and cholesterol's role in membrane organization is crucial.

Purpose of the Study:

  • To investigate the fluid-phase behavior of binary mixtures of cholesterol and phosphatidylcholines.
  • To elucidate the location and interactions of cholesterol within different fluid phases of lipid bilayers.

Main Methods:

  • Utilized magnetic resonance techniques, including electron spin resonance (ESR) and solid-state high-resolution nuclear magnetic resonance (NMR).
  • Employed phospholipid biradicals for ESR to resolve immiscible fluid phases.

Related Experiment Videos

  • Measured isotropic chemical shifts and spin label-enhanced spin-lattice relaxation rates of 13C nuclei.

    • Main Results:

    • Resolved two immiscible fluid phases in dipalmitoylphosphatidylcholine-cholesterol mixtures using ESR.
    • Identified evidence for a hydrogen bond between cholesterol's 3 beta-hydroxyl group and the phospholipid's sn-2 carbonyl carbon via NMR.
    • Determined cholesterol's location in the bilayer: spanning the bilayer in the cholesterol-poor phase and distributed across both monolayers in the cholesterol-rich phase.

    Conclusions:

    • Cholesterol's interaction with phosphatidylcholines leads to distinct fluid phases with specific molecular arrangements.
    • A hydrogen bond likely contributes to the interaction between cholesterol and phospholipids.
    • Cholesterol's localization within the bilayer is phase-dependent, impacting membrane structure and dynamics.