Kinetic and structural aspects of reconstitution of phosphatidylcholine vesicles by dilution of phosphatidylcholine-sodium cholate mixed micelles

S. Almog, D. Lichtenberg*, T. Kushnir, S. Nir

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


Dilution of mixed micellar dispersions of egg phosphatidylcholine (PC) and sodium cholate beyond a critical value results in formation of cholate-containing PC vesicles. The structure of the resultant vesicles and some mechanistic aspects of this process have been investigated by the use of light scattering and nuclear magnetic resonance techniques. The main findings and conclusions are the following: (1) Both the state of aggregation (micellar or vesicular) and the apparent equilibrium size distribution of micelles or vesicles obtained by dilution of the PC-cholate mixed micellar dispersions are a function of the cholate to PC molar ratio in the mixed aggregates (micelles or vesicles). When this effective ratio (Re) is higher than 0.4, the dispersion is micellar, and the size of the mixed micelles increases with decreasing Re; when Re < 0.3, the dispersion is essentially vesicular, and the mean hydrodynamic radius of the vesicles is an increasing function of Re; in dispersions with 0.3 < Re< 0.4, mixed micelles and vesicles coexist. (2) Addition of cholate to vesicular dispersions, to Re values below 0.3, results in vesicle size growth through a concentration-independent lipid-exchange mechanism. Addition of cholate to higher Re values results in micellization (solubilization) of the vesicles. On the other hand, dilution of vesicular dispersions does not affect the size of the vesicles. (3) Apparent equilibration of a mixed micellar dispersion following dilution to Re values below 0.3 is slow (many hours). The overall process involves a series of three subsequent categories of steps: (i) a rapid (~1-2 min) prevesiculation equilibration of micellar sizes; (ii) a relatively rapid (20–30 min) membrane closure due to cholate depletion from large (“mixed-disc”) mixed micelles (this results in the formation of small unilamellar vesicles); (iii) a slow postvesiculation size growth of the initially formed small cholate-containing vesicles. This series of vesicle size growth processes probably involves a net lipid exchange from small vesicles to larger (more stable) ones, through a residual fraction of PC-cholate mixed micelles. We suggest that for any given Re apparent equilibrium is approached when the “offrate” of PC molecules from the vesicles becomes extremely slow. Thus, the apparent equilibrium size distribution may be a metastable state of aggregation.

Original languageEnglish
Pages (from-to)2597-2605
Number of pages9
Issue number9
StatePublished - May 1986


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