Aggregation and dynamics of oligocholate transporters in phospholipid bilayers revealed by solid-state NMR spectroscopy
Macrocycles made of cholate building blocks were previously found to transport glucose readily across lipid bilayers. In this study, an 15N, 13Cα-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. 13C-detected 1H 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. © 2012 American Chemical Society.
Publication Source (Journal or Book title)
Wang, T., Widanapathirana, L., Zhao, Y., & Hong, M. (2012). Aggregation and dynamics of oligocholate transporters in phospholipid bilayers revealed by solid-state NMR spectroscopy. Langmuir, 28 (49), 17071-17078. https://doi.org/10.1021/la303661p