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. Two distinct regimes of aggregation behaviour are observed as the composition of charged lipids in the vesicles is varied. At low vesicle charge, electrostatic aggregation is followed by a deaggregation process to a size that is slightly larger than the initial vesicle size; at higher vesicle charges, aggregation is observed with no subsequent deaggregation. We study the effects of vesicle size and ionic strength of the aqueous solvent on the aggregation kinetics: at low charge, smaller vesicles and higher ionic strengths result in faster deaggregation. Fluorescence assays to probe leakage and fusion events, and electrophoretic measurements supplement the aggregation data to provide our proposed picture of the kinetic evolution of the system in the two behavioural regimes of aggregation. At high charge, rapid vesicle fusion is followed by flocculation. At low charge, electrostatic aggregation leads to some neutralization of the vesicles by exchange of lipids in the outer monolayers, the ensuing deaggregation is a result of vesicle rupture. This simple model system 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.

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