title: Interaction of Bile Salts with Model Membranes Mimicking the Gastrointestinal Epithelium: A Study by Isothermal Titration Calorimetry.
abstract: Bile salts (BS) are biosurfactants synthesized in the liver and secreted into the intestinal lumen where they solubilize cholesterol and other hydrophobic compounds facilitating their gastrointestinal absorption. Partition of BS toward biomembranes is an important step in both processes. Depending on the loading of the secreted BS micelles with endogeneous cholesterol and on the amount of cholesterol from diet, this may lead to the excretion or absorption of cholesterol, from cholesterol-saturated membranes in the liver or to gastrointestinal membranes, respectively. The partition of BS toward the gastrointestinal membranes may also affect the barrier properties of those membranes affecting the permeability for hydrophobic and amphiphilic compounds. Two important parameters in the interaction of the distinct BS with biomembranes are their partition coefficient and the rate of diffusion through the membrane. Altogether, they allow the calculation of BS local concentrations in the membrane as well as their asymmetry in both membrane leaflets. The local concentration and, most importantly, its asymmetric distribution in the bilayer are a measure of induced membrane perturbation, which is expected to significantly affect its properties as a cholesterol donor and hydrophobic barrier. In this work we have characterized the partition of several BS, nonconjugated and conjugated with glycine, to large unilamellar vesicles (LUVs) in the liquid-disordered phase and with liquid-ordered/liquid-disordered phase coexistence, using isothermal titration calorimetry (ITC). The partition into the liquid-disordered bilayer was characterized by large partition coefficients and favored by enthalpy, while association with the more ordered membrane was weak and driven only by the hydrophobic effect. The trihydroxy BS partitions less efficiently toward the membranes but shows faster translocation rates, in agreement with a membrane protective effect of those BS. The rate of translocation through the more ordered membrane was faster, indicating accumulation of BS at specific locations in this membrane.
authors.affiliation: Department of Chemistry, University of Coimbra , 3004-535 Coimbra, Portugal.|Coimbra Chemistry Center, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Filipe M
authors.initials: FM
authors.lastname: Coreta-Gomes
authors.affiliation: Department of Chemistry, University of Coimbra , 3004-535 Coimbra, Portugal.|Coimbra Chemistry Center, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Patrícia A T
authors.initials: PA
authors.lastname: Martins
authors.affiliation: Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit IQFR-CSIC-BIFI and Department of Biochemistry and Molecular and Cell Biology, Universidad de Zaragoza , 50018 Zaragoza, Spain.|Fundación ARAID, Diputación General de Aragón, 500018 Zaragoza, Spain.
authors.forename: Adrián
authors.initials: A
authors.lastname: Velazquez-Campoy
authors.affiliation: Department of Chemistry, University of Coimbra , 3004-535 Coimbra, Portugal.|Coimbra Chemistry Center, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Winchil L C
authors.initials: WL
authors.lastname: Vaz
authors.affiliation: Coimbra Chemistry Center, University of Coimbra , 3004-535 Coimbra, Portugal.|Department of Life Sciences, Faculty of Science and Technology, University of Coimbra , 3001-401 Coimbra, Portugal.
authors.forename: Carlos F G
authors.initials: CF
authors.lastname: Geraldes
authors.affiliation: Department of Chemistry, University of Coimbra , 3004-535 Coimbra, Portugal.|Coimbra Chemistry Center, University of Coimbra , 3004-535 Coimbra, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Moreno
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D005753:Gastric Mucosa / Q000737:chemistry*; D007413:Intestinal Mucosa / Q000737:chemistry*; D008567:Membranes, Artificial
chemical_list: D001647:Bile Acids and Salts; D008567:Membranes, Artificial