Order from disorder, corralling cholesterol with chaotic lipids - The role of polyunsaturated lipids in membrane raft formation
Order from disorder, corralling cholesterol with chaotic lipids - The role of polyunsaturated lipids in membrane raft formation
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DOI：
10.1016/j.chemphyslip.2004.09.007
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Stillwell, W
中科院分区：
文献类型：
--
作者：
Wassall, SR;Brzustowicz, MR;Stillwell, W
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 H-2 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- [H-2(3)]palmitoyl-2-docosahexaenoylphosphatidylethanolamine ([H-2(31)]16:0-22:6PE) relative to 1-[H-2(31)]palmitoyl- 2-oleoylphosphatidylethanolamine ([H-2(31)]16:0-18:lPE) is identified by H-2 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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
