Order from disorder, corralling cholesterol with chaotic lipids. The role of polyunsaturated lipids in membrane raft formation.

Abstract:

:A myriad of health benefits including the prevention of cancer and heart disease accompanies consumption of polyunsaturated fatty acids (PUFA). Of special importance is the omega-3-PUFA docosahexaenoic acid (DHA), with 22 carbons and six double bonds that constitute the most highly unsaturated fatty acid naturally occurring. Our experiments target the membrane as a likely site of action and focus upon the interaction of cholesterol with PUFA-containing phospholipids. They support the idea that steric incompatibility of the rigid steroid moiety for highly disordered PUFA chains promotes lateral segregation of lipids into PUFA-rich/sterol-poor and PUFA-poor/sterol-rich regions. Solid state 2H NMR and X-ray diffraction demonstrate that the solubility of cholesterol is low in polyunsaturated bilayers. In mixed membranes of phosphatidylethanolamine (PE) with the lipid raft-forming molecules sphingomyelin (SM) and cholesterol, diminished affinity of the sterol for 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylethanolamine ([2H31]16:0-22:6PE) relative to 1-[2H31]palmitoyl-2-oleoylphosphatidylethanolamine ([2H31]16:0-18:1PE) is identified by 2H NMR order parameters. Here, lies the origin of a potential biological advantage of the relatively modest increase in PUFA content of plasma membranes that would be conferred by dietary supplementation. We hypothesize that the enhanced propensity to form SM-/cholesterol-rich rafts as well as PUFA-rich/cholesterol-poor microdomains would modify the function of proteins for which these respective regions provide a platform.

journal_name

Chem Phys Lipids

authors

Wassall SR,Brzustowicz MR,Shaikh SR,Cherezov V,Caffrey M,Stillwell W

doi

10.1016/j.chemphyslip.2004.09.007

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

79-88

issue

1

eissn

0009-3084

issn

1873-2941

pii

S0009-3084(04)00140-9

journal_volume

132

pub_type

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