title: Interaction of Cytotoxic and Cytoprotective Bile Acids with Model Membranes: Influence of the Membrane Composition.
abstract: To understand the role of bile acids (BAs) in cell function, many authors have investigated their effect on biomembrane models which are less complex systems, but there are still many open questions. The present study aims to contribute for the deepening of the knowledge of the interaction between BAs and model membranes, in particular, focusing on the effect of BA mixtures. The cytotoxic deoxycholic acid (DCA), the cytoprotective ursodeoxycholic acid (UDCA), and the equimolar mixture (DCA + UDCA) were investigated. Monolayers and liposomes were taken as model membranes with two lipid compositions: an equimolar mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol)) traditionally associated with the formation of lipid rafts and an equimolar POPC/SM binary mixture. The obtained results showed that DCA causes the fluidization of monolayers and bilayers, leading to the eventual rupture of POPC/SM liposomes at high concentration. UDCA may provide a stabilization of POPC/SM membranes but has a negligible effect on the Chol-containing liposomes. In the case of equimolar mixture DCA/UDCA, the interactions depend not only on the lipid composition but also on the design of the experiment. The BA mixture has a greater impact on the monolayers than do pure BAs, suggesting a cooperative DCA-UDCA interaction that enhances the penetration of UDCA in both POPC/SM and POPC/SM/Chol monolayers. For the bilayers, the presence of UDCA in the mixture decreases the disturbing effect of DCA.
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Esteves
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ferreira
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.|‡Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Kozica
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: A C
authors.initials: AC
authors.lastname: Fernandes
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Gonçalves da Silva
authors.affiliation: †Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
authors.forename: B
authors.initials: B
authors.lastname: Saramago
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D003840:Deoxycholic Acid / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000737:chemistry*; D013109:Sphingomyelins / Q000737:chemistry*; D014580:Ursodeoxycholic Acid / Q000737:chemistry*
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine