title: How polyunsaturated fatty acids modify molecular organization in membranes: insight from NMR studies of model systems.
abstract: Marine long chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are bioactive molecules with clinical applications for the treatment of several diseases. In order to effectively translate these molecules into clinical trials, it is essential to establish the underlying mechanisms for n-3 PUFA. This review focuses on efforts to understand how EPA and DHA, upon incorporation into plasma membrane phospholipids, remodel the molecular organization of cholesterol-enriched lipid microdomains. We first give an overview of results from studies on cells. Paradoxical data generated from mouse studies indicate that EPA and DHA incorporate into lipid microdomains, yet in spite of their high disorder increase molecular order within the domain. We then spotlight the utility of solid state (2)H NMR spectroscopy of model bilayers as a tool for elucidating underlying mechanisms by which n-3 PUFA-containing phospholipids can regulate molecular organization of lipid microdomains. Evidence is presented demonstrating that n-3 PUFA exert differential structural effects when incorporated into phosphatidylethanolamines (PE) compared to phosphatidylcholines (PC), which explains some of the conflicting results observed in vivo. Recent studies that reveal differences between the interactions of EPA and DHA with lipid microdomains, potentially reflecting a differential in bioactivity, are finally described. Overall, we highlight the notion that NMR experiments on model membranes suggest a complex model by which n-3 PUFA reorganize lipid microdomains in vivo.
authors.affiliation: Department of Biochemistry & Molecular Biology, East Carolina Diabetes and Obesity Institute, East Carolina University, 115 Heart Drive, Room 4117, Mail Stop 743, Greenville, NC 27834, USA.
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.affiliation: Department of Physics, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202-3273, USA.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Kinnun
authors.affiliation: Department of Physics, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202-3273, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Leng
authors.affiliation: Department of Physics, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202-3273, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Williams
authors.affiliation: Department of Physics, Indiana University-Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202-3273, USA. Electronic address: swassall@iupui.edu.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wassall
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D021962:Membrane Microdomains / Q000737:chemistry; D051379:Mice; D010743:Phospholipids / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry
chemical_list: D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D013109:Sphingomyelins; D002784:Cholesterol
keywords: Docosahexaenoic acid (DHA); Eicosapentaenoic acid (EPA); Lipid microdomain; Lipid raft; Solid state (2)H NMR