Kinetic pathway of spontaneous vesicle formation

– The spontaneous formation of lipid vesicles (liposomes) in aqueous lecithin/bile salt mixtures is studied using time-resolved static and dynamic light scattering. These measurements reveal a strong dependence of the kinetic rates and end-state liposome properties on total amphiphile concentration and, even more pronounced, on ionic strength. The observed trends contradict equilibrium calculations, but are in quantitative agreement with a kinetic model that we present. This model identifies the key kinetic steps during vesicle formation: rapid formation of disc-like intermediate micelles, growth of these micelles and closure to form vesicles. This work offers conclusive evidence for kinetic rather than thermodynamic control of the end-state properties. While the equilibrium behaviour of surfactant aggregates is well studied [1, 2], their nonequilibrium behaviour has not been much addressed. Particularly interesting are transformations between different monolayer and bilayer topologies; a classical example is the micellevesicle transition [3, 4]. It is, e.g., an important route to preparing lipid vesicles (liposomes) known as “reconstitution”: a soluble detergent is removed from lipid-detergent micelles by dialysis or dilution, resulting in spontaneous vesicle formation [4,5]. This procedure is widely applied and, more generally, the properties of vesicles are extensively studied in a number of different systems. Nevertheless, there has been only limited understanding of their formation [5–11] and what determines their final (“end-state”) properties; equilibrium calculations [12] give the wrong trends for the dependence of liposome size on bilayer composition [13–17]. This suggests a kinetic mechanism with the end-state vesicles being metastable structures that cannot achieve thermal equilibrium on observable timescales. The question whether vesicles represent equilibrium structures is, however, not unambiguously solved [13]. By combining light scattering experiments with a quantitative kinetic model (for full details see [18]), we conclusively establish a kinetic mechanism, at least for the systems we study, which comprise mixtures of lipid (lecithin) and natural detergent (bile salt). (∗) E-mail: [email protected]