Interaction of two bile acids, a cytotoxic and a cytoprotective, with biomembrane models

Bile acids (BA) are naturally-occurring detergents that solubilize dietary lipids in the intestinal tract. However, they are involved in the triggering of diseases like colon cancer and other liver problems. This study has the purpose of investigating how these acids interact with cell membranes and their effects on them. We studied the effects of two bile acids, a cytotoxic (DCA) and other cytoprotective (UDCA) and the equimolar mixture of the two bile acids on biomembranare models. The lipid composition was chosen with the purpose of mimicking lipid rafts, which are cell membrane domains involved in several cell events. This way, an equimolar mixture of 1-palmitoyl-2oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and cholesterol (Chol) was used as a model for lipid raft. In order to perceive the influence of cholesterol in bile acid – lipid interactions a 1:1 POPC/SM mixture was also utilized. The experimental techniques used were: Langmuir trough (lipid monolayer); Quartz Crystal Microbalance with Dissipation (QCM-D) (supported liposomes); Differential Scanning Calorimetry (DSC) and Phosphorus Nuclear Magnetic Resonance (31P-NMR) (liposomes in suspension). With this work we concluded that DCA causes fluidization of the membrane models studied, promoting the rupture of POPC/SM liposomes, for a 1000 μM concentration. UDCA has little influence on the systems studied, and might provide a stabilization of membranes by interaction with phospholipid headgroups. The equimolar mixture DCA/UDCA shows that, in general, there is a cooperation between the two acids: the fluidizing effect of DCA promotes incorporation of UDCA.