Bile acid/phosphatidylcholine interactions in mixed monomolecular layers: differences in condensation effects but not interfacial orientation between hydrophobic and hydrophilic bile acid species.

Monomolecular layers of undissociated bile acids and membrane lipids at the air/water interface serve as useful models for the interactions between fully ionized bile salts and physiological membranes. Employing an automated Langmuir-Pockels surface balance, surface pressures and dipole moments were measured as functions of molecular area for six dihydroxy bile acids: ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), allodeoxycholic acid (alloDCA), and 7 alpha,12 alpha-dihydroxycholanoic acid (7,12-OH-DCA), individually and in mixed mono-molecular layers with 1-palmitoyl-2-oleoyl-sn-3-glycerophosphatidylcholine (POPC) with and without cholesterol on a 5 M NaCl subphase at pH 2. In general, monolayers of hydrophilic bile acids (UDCA, HDCA) had lower collapse pressures and surface dipole moments than hydrophobic bile acids (CDCA approximately DCA approximately alloDCA < 7,12-OH-DCA). In binary mixtures with POPC, all bile acids including the synthetic 7,12-OH-DCA and the uncommon alloDCA condensed mixed monomolecular layers, with the degree of condensation correlating positively with bile acid hydrophobicity. In contrast, none of the bile acids caused further condensation of condensed POPC/cholesterol monomolecular layers. Surface dipole moments of binary bile acid/POPC +/- cholesterol mixtures demonstrated strict additivity, implying that no change in molecular orientation of the interface occurred over film compositions that varied from 0 to 100% bile acid. We conclude that the long axes of the steroid nuclei of dihydroxy bile acids remain parallel to the interface in mixed bile acid/POPC +/- cholesterol monomolecular layers under all conditions. We infer that fully dissociated hydrophobic and, to a lesser extent, hydrophilic bile salts condense phospholipid monomolecular layers and membranes in a similar fashion.