title: Aggregation and dynamics of oligocholate transporters in phospholipid bilayers revealed by solid-state NMR spectroscopy.
abstract: Macrocycles made of cholate building blocks were previously found to transport glucose readily across lipid bilayers. In this study, an (15)N, (13)Cα-labeled glycine was inserted into a cyclic cholate trimer and attached at the end of a linear trimer, respectively. The isotopic labeling allowed us to use solid-state NMR spectroscopy to study the dynamics, aggregation, and depth of insertion of these compounds in lipid membranes. The cyclic compound was found to be mostly immobilized in DLPC, POPC/POPG, and POPC/POPG/cholesterol membranes, whereas the linear trimer displayed large-amplitude motion that depended on the membrane thickness and viscosity. (13)C-detected (1)H spin diffusion experiments revealed the depth of insertion of the compounds in the membranes, as well as their contact with water molecules. The data support a consistent stacking model for the cholate macrocycles in lipid membranes, driven by the hydrophobic interactions of the water molecules in the interior of the macrocycles. The study also shows a strong preference of the linear trimer for the membrane surface, consistent with its lack of transport activity in earlier liposome leakage assays.
authors.affiliation: Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, USA.
authors.forename: Tuo
authors.initials: T
authors.lastname: Wang
authors.forename: Lakmini
authors.initials: L
authors.lastname: Widanapathirana
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
mesh_terms: D001692:Biological Transport; D040761:Biomimetic Materials / Q000737:chemistry*; D002247:Carbon Isotopes; D020355:Cholates / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D004058:Diffusion; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D026901:Membrane Transport Proteins / Q000737:chemistry; D008958:Models, Molecular; D009587:Nitrogen Isotopes; D010713:Phosphatidylcholines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D058105:Polymerization; D014867:Water
chemical_list: D002247:Carbon Isotopes; D020355:Cholates; D008051:Lipid Bilayers; D026901:Membrane Transport Proteins; D009587:Nitrogen Isotopes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D014867:Water; C002448:1,2-linoleoylphosphatidylcholine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine