1-palmitoyl-2-oleoylglycero-3-phosphoglycerol and 1-2-linoleoylphosphatidylcholine

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.

Topics: Biological Transport; Biomimetic Materials; Carbon Isotopes; Cholates; Cholesterol; Diffusion; Kinetics; Lipid Bilayers; Magnetic Resonance Spectroscopy; Membrane Transport Proteins; Models, Molecular; Nitrogen Isotopes; Phosphatidylcholines; Phosphatidylglycerols; Polymerization; Water