Solubilization of negatively charged DPPC/DPPG liposomes by bile salts

• Published in: Journal of colloid and interface science 2004-11, Vol.279 (2), p.559-571
• Main Authors: Hildebrand, Annegret, Beyer, Katja, Neubert, Reinhard, Garidel, Patrick, Blume, Alfred
• Format: Article
• Language: English
• Subjects: 1,2-Dipalmitoylphosphatidylcholine - chemistry; Bile Acids and Salts - chemistry; Bile salt; Calorimetry, Differential Scanning; Chemistry; Colloidal state and disperse state; Deoxycholic Acid - chemistry; Differential scanning calorimetry; Dynamic light scattering; Exact sciences and technology; General and physical chemistry; Isothermal titration calorimetry; Light; Liposome; Liposomes - chemistry; Membranes; Membranes, Artificial; Micelles. Thin films; Molecular Conformation; Phosphatidylcholine; Phosphatidylglycerol; Phosphatidylglycerols - chemistry; Scattering, Radiation; Sodium Chloride - chemistry; Sodium Cholate - chemistry; Solubility; Solubilization; Surface Properties; Temperature; Thermodynamics; Vesicle–micelle transition
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2004.06.085

The interactions of the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC) in 0.1 M NaCl (pH 7.4) with membranes composed of 1,2-dipalmitoyl- sn-glycero-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl- sn-glycero-3-phosphatidylglycerol (DPPG) and mixtures of DPPC and DPPG at molar ratios of 3:1 and 1:1 were studied by means of high-sensitivity isothermal titration calorimetry (ITC), dynamic light scattering (DLS), and differential scanning calorimetry (DSC). The partition coefficients and the transfer enthalpies for the incorporation of bile salt molecules into the phospholipid membranes were determined by ITC. The vesicle-to-micelle transition was investigated by ITC, DLS, and DSC. The phase boundaries for the saturation of the vesicles and their complete solubilization established by ITC were in general agreement with DLS data, but systematic differences could be seen due to the difference in detected physical quantities. Electrostatic repulsion effects between the negatively charged bile salt molecules and the negatively charged membrane surfaces are not limiting factors for the vesicle-to-micelle transition. The membrane packing constraints of the phospholipid molecules and the associated spontaneous curvature of the vesicles play the dominant role. DPPG vesicles are transformed by the bile salts into mixed micelles more easily or similarly compared to DPPC vesicles. The saturation of mixed DPPC/DPPG vesicles requires less bile salt, but to induce the solubilization of the liposomes, significantly higher amounts of bile salt are needed compared to the concentrations required for the solubilization of the pure phospholipid systems. The different solubilization behavior of DPPC/DPPG liposomes compared to the pure liposomes could be due to a specific “extraction” of DPPG into the mixed micelles in the coexistence region.