Dynamic interaction between oppositely charged vesicles: Aggregation, lipid mixing, and disaggregation

We investigated dynamic interactions between oppositely charged small unilamellar vesicles using positively charged vesicles containing 1,2-dioleoyl-3-trimethylammonium-propane or 3β-[N  -(N′,N′N′,N′-dimethylaminoethane)-carbamoyl] cholesterol and negatively charged vesicles containing L-α-phosphatidyl-DL-glycerol. Aggregation, lipid bilayer mixing, contents mixing and contents leakage were systematically examined using optical density measurements, fluorescence resonance energy transfer assays, fluorescence quenching assays, light-scattering analyses, and freeze-fracture transmission electron microscopy. The oppositely charged vesicles aggregated immediately. Lipid mixing was observed, but there was no mixing of the contents. The vesicle aggregates disaggregated spontaneously after several minutes. The surface potential of the disaggregated vesicles was neutralized. From these results, we infer that the lipids in the external monolayers were exchanged between the oppositely charged vesicles while the internal monolayers remained intact. The two types of cationic lipids used exhibited different speeds of disaggregation.

Graphical abstractMixing positively charged PC/DOTAP (70/30 molar ratio) vesicles with negatively charged PC/PG (70/30) vesicles induced rapid aggregation followed by spontaneous disaggregation after several minutes.Figure optionsDownload full-size imageDownload as PowerPoint slide