STRUCTURAL MECHANISMS OF BILE SALT-INDUCED GROWTH OF SMALL UNILAMELLAR CHOLESTEROL - LECITHIN VESICLES

The liver secretes cholesterol and lecithin in the form of mixed vesic les during the formation of bile. When exposed to bile salts, these me tastable vesicles undergo various structural rearrangements. We have e xamined the effects of three different bile salts, taurocholate (TC), tauroursodeoxycholate (TUDC), and taurodeoxycholate (TDC), on the stab ility of sonicated lecithin vesicles containing various amounts of cho lesterol. Vesicle growth was probed by turbidity measurements, quasi-e lastic Light scattering, and a resonance energy transfer lipid-mixing assay. Leakage of internal contents was monitored by encapsulation of fluorescence probes in vesicles. At low bile salt-to-lecithin ratios ( TC/L or TUDC/L < 1), pure lecithin vesicles do not grow, but exhibit s low intervesicular mixing of lipids as well as gradual leakage. At hig h BS/L (TC/L or TUDC/L > 5), pure lecithin vesicles are solubilized in to mixed micelles with a concomitant decrease in the overall particle size. In this regime, extensive leakage and Lipid mixing occur instant aneously after exposure to bile salt. At intermediate BS/L (1 < TC/L o r TUDC/L ( 5), vesicles grow with time, and the rates of both leakage and lipid mixing are rapid. The data suggest that vesicles grow by the transfer of lecithin and cholesterol via diffusion in the aqueous med ium. The addition of cholesterol to lecithin vesicles reduces leakage dramatically and increases the amount of BS required for complete solu bilization of vesicles. The more hydrophobic TDC induces vesicle growt h at a lower BS/L than does TC or TUDC. These results demonstrate the physiologic forms of lipid microstructures during bile formation and e xplain how the hydrophilic-hydrophobic balance of BS mixtures may prof oundly affect the early stages of CH gallstone formation.