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The Kinetic Evolution of Mixtures of Anionic and Cationic Lipid Vesicles

Paul A. Beales and T. Kyle Vanderlick. Department of Chemical Engineering, Princeton University, Engineering Quadrangle, Princeton, NJ 08544

We investigate the kinetics of the interactions between populations of anionic and cationic lipid vesicles. Cationic vesicles are composed of mixtures of zwitterionic POPC and positively charged DOTAP. Anionic vesicles are composed of mixtures of POPC and negatively charged DOPG. We observe two distinct regimes of aggregation behaviour as the composition of charged lipids in the vesicles is varied. At low vesicle charge, electrostatic aggregation is followed by a deaggregation process. The rate of deaggregation increases with increasing charge of the vesicles. At higher vesicle charges, rapid vesicle fusion leads to an initially observed aggregate size that gradually increases with time due to flocculation of these lipid aggregates. The rate of flocculation increases with the proportion of charged lipid per vesicle. Fluorescence assays to probe lipid mixing and fusion events and electrophoretic measurements supplement the aggregation data to provide a complete picture of the kinetic evolution of the system in the two behavioural regimes of aggregation. This study provides insight into the fundamental phenomenology of a system of oppositely charged colloidal particles where the colloids (i.e. vesicles) can exhibit a rich variety of behaviours. This simple model system also has application to gene therapy where cationic lipids are used to deliver DNA across the anionic cell membrane: our results may help point to new directions in improving transfection efficiency.