title: Kinetic and Thermodynamic Analysis of Cholesterol Transfer between Phospholipid Vesicles and Nanodiscs.
abstract: We investigated interparticle transfer of cholesterol (Chol) between large unilamellar vesicles (LUVs) and phospholipid bilayer nanodiscs. The Chol transfer rate from LUVs to nanodiscs was decreased by an increase in the Chol content or incorporation of sphingomyelin in donor phosphatidylcholine/Chol LUVs but was not influenced by the lipid composition of acceptor particles. These results suggest that Chol dissociation from the lipid bilayer into aqueous phase is the rate-limiting step of the transfer and that the process depends on the fluidity of the donor membranes. The Chol dissociation rate from nanodiscs was faster than that from LUVs with similar lipid composition. Chol preferably partitioned to LUVs rather than nanodiscs, which is consistent with the faster dissociation rate from nanodiscs. The activation energy of Chol dissociation from nanodiscs was 1.7 kJ/mol lower than that from LUV, which was brought by increased (less negative) activation entropy and enthalpy. In addition, fluorescence lifetime and anisotropy data revealed that the lipid bilayer of nanodiscs is more tightly packed than that of LUVs. These results suggest that the tighter lipid packing in nanodiscs destabilizes the Chol-containing bilayer by reducing the entropy, which facilitates Chol dissociation.
authors.affiliation: †Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsuzaki
authors.affiliation: ‡Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minami-Tamagaki-cho, Suzuka, Mie 513-8670, Japan.
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Handa
authors.affiliation: §Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakano
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D019277:Entropy; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D053835:Unilamellar Liposomes; D002784:Cholesterol