title: 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.
authors.affiliation: Department of Physics, Indiana University Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202-3273, USA. swassall@iupui.edu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wassall
authors.forename: Michael R
authors.initials: MR
authors.lastname: Brzustowicz
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: Vadim
authors.initials: V
authors.lastname: Cherezov
authors.forename: Martin
authors.initials: M
authors.lastname: Caffrey
authors.forename: William
authors.initials: W
authors.lastname: Stillwell
mesh_terms: D004281:Docosahexaenoic Acids / Q000737:chemistry*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D021962:Membrane Microdomains / Q000737:chemistry*; D008968:Molecular Conformation; D017711:Nonlinear Dynamics; D044367:Phase Transition; D010743:Phospholipids / Q000737:chemistry*; D012995:Solubility
chemical_list: D005231:Fatty Acids, Unsaturated; D008051:Lipid Bilayers; D010743:Phospholipids; D004281:Docosahexaenoic Acids