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

Norbert Kučerka, Drew Marquardt, Thad A. Harroun, Mu Ping Nieh, Stephen R. Wassall, John Katsaras

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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.

Original languageEnglish
Pages (from-to)16358-16359
Number of pages2
JournalJournal of the American Chemical Society
Volume131
Issue number45
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Dive into the research topics of 'The functional significance of lipid diversity: Orientation of cholesterol in bilayers is determined by lipid species'. Together they form a unique fingerprint.

Cite this