The functional significance of lipid diversity: Orientation of cholesterol in bilayers is determined by lipid species

Document Type

Article

Publication Date

11-27-2009

Publication Title

Journal of the American Chemical Society

Volume

131

Issue

45

First Page

16358

Last Page

16359

Abstract

(Figure Presented) The chemical diversity of lipids and their complex arrangements in supramolecular assemblies are in stark contrast to our previous notions of them as passive structural components. For example, in plasma membranes, sphingolipids are primarily located in the outer monolayer, whereas unsaturated phospholipids are more abundant in the inner leaflet. Our recent results offer a direct contribution to the importance of lipid diversity in biological membranes. We have studied the location of cholesterol within polyunsaturated fatty acid (PUFA) bilayers doped with different amounts of monounsaturated (POPC) or disaturated (DMPC) lipids. Using deuterium labeling and neutron diffraction, we have found that in PUFA bilayers, cholesterol can be flipped from its known position in the bilayer center to its commonly assumed upright orientation simply by varying the amount of POPC. Although it takes 50 mol % POPC to flip cholesterol in PUFA bilayers, the same effect is achieved with only ∼5 mol % DMPC, elegantly emphasizing cholesterol's affinity for saturated chains. It also suggests that the presence of PUFA in the inner leaflet of a cellular bilayer may enhance the transfer of cholesterol to the outer layer, potentially modifying raft composition and the local function of a membrane. © 2009 American Chemical Society.

DOI

10.1021/ja907659u

ISSN

00027863

PubMed ID

19902974

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