Effect of Cholesterol on Liposome Stability to Ultrasonic Disintegration and Sodium Cholate Solubilization

Liposome disintegration by either ultrasonic vibration or sodium cholate solubilization was investigated as a function of cholesterol (CH) content in the egg phosphatidylcholine (PC) liposome membrane. Turbidity changes were used as an indication of the membrane stability to these stresses. First-order disintegration constants (κufor ultrasonic stress and κsfor sodium cholate solubilization) were calculated to evaluate the membrane stability. A plot of κu against membrane CH content gave a sigmoidal curve on which inflection points occurred at about 15 mol% and 33 mol% CH. In contrast, the plot of κs against membrane CH content gave a biphasic curve with only one inflection point at about 17 mol% CH. These results can be explained in terms of the molecular packing model of phospholipids and CH proposed by Presti et al. (Biochemistry, 21, 3831 (1982)). Disintegration by ultrasonic stress was little affected by the accumulation of CH-rich domains up to 15 mol% CH, but disintegration by sodium cholate was abruptly suppressed in the same CH. content range. These results indicate that the mechanisms of disintegration of CH-rich domains and interfacial boundary phospholipid are entirely different between the two stresses. In the liposome disintegration by sodium cholate, it was suggested that the penetration-saturation step of the surfactant molecule into the bilayer is rate-determining for pure PC liposomes, while the lamellar-micellar transition step is rate-determining for CH-rich liposomes.