Bjm. Vandeheijning et al., THE EFFECTS OF BILE-SALT HYDROPHOBICITY ON MODEL BILE VESICLE MORPHOLOGY, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1212(2), 1994, pp. 203-210
The addition of bile salts to vesicles supersaturated with cholesterol
induces cholesterol precipitation, an important step in the formation
of cholesterol gallstones. To investigate the effects of bile salt hy
drophobicity on vesicle morphology, vesicles obtained from supersatura
ted model bile by density gradient ultracentrifugation, were incubated
with mixtures of deoxycholate (DC) and ursodeoxycholate (UDC) with a
constant total bile salt concentration of 30 mM but with a varying hyd
rophobicity index ranging from - 0.31 (UDC alone) up to + 0.72 (DC alo
ne) depending on the composition of the mixture. Five days after addit
ion of bile salts to vesicles, cholesterol precipitation was determine
d microscopically and incubation samples were again subjected to ultra
centrifugation to assess the lipid distribution among residual vesicle
s, mixed micelles, and cholesterol crystals. Structure and size of the
isolated residual vesicles were studied by freeze fracture electron m
icroscopy. The control, and samples exposed to hydrophilic bile salt m
ixtures, consisted of unilamellar vesicles of which more than 75% had
a diameter of 50-80 nm. After addition of increasingly hydrophobic bil
e salt mixtures, multilamellar vesicles with progressively greater dia
meters (up to 1300 nm) were found, suggesting that vesicle fusion and
aggregation took place and might hence be important in the cholesterol
precipitation process. Accordingly, crystallization was positively co
rrelated with bile salt hydrophobicity. We conclude that cholesterol c
rystallization from vesicles depends on the hydrophobicity of the bile
salts added, and apparently occurs from fused or aggregated vesicles
of extended magnitude and with a multilamellar constitution.