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Biophysical Journal 85:1624-1646 (2003)
© 2003 The Biophysical Society

Kinetics of the Micelle-to-Vesicle Transition: Aqueous Lecithin-Bile Salt Mixtures

J. Leng, S. U. Egelhaaf and M. E. Cates

The University of Edinburgh, School of Physics, King's Buildings, Edinburgh EH9 3JZ, United Kingdom

Correspondence: Address reprint requests to Stefan U. Egelhaaf, Tel.: +44-131-6505291; Fax: +44-131-6505902; E-mail: s.u.egelhaaf{at}ed.ac.uk.

Important routes to lipid vesicles (liposomes) are detergent removal techniques, such as dialysis or dilution. Although they are widely applied, there has been only limited understanding about the structural evolution during the formation of vesicles and the parameters that determine their properties. We use time-resolved static and dynamic light scattering to study vesicle formation in aqueous lecithin-bile salt mixtures. The kinetic rates and vesicle sizes are found to strongly depend on total amphiphile concentration and, even more pronounced, on ionic strength. The observed trends contradict equilibrium calculations, but are in agreement with a kinetic model that we present. This model identifies the key kinetic steps during vesicle formation: rapid formation of disklike intermediate micelles, growth of these metastable micelles, and their closure to form vesicles once line tension dominates bending energy. A comparison of the rates of growth and closure provides a kinetic criterion for the critical size at which disks close and thus for the vesicle size. The model suggests that liposomes are nonequilibrium, kinetically trapped structures of very long lifetime. Their properties are hence controlled by kinetics rather than thermodynamics.




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