Self-limiting aggregation of phospholipid vesicles

Lipid vesicles are widely used as model systems to study biological membranes. The self-assembly of such vesicles into vesicle pairs provides further opportunity to study interactions between membranes. However, formation of vesicle pairs, while subsequently keeping their colloidal stability intact, is challenging. Here, we report on three strategies that lead to stable finite-sized aggregates of phospholipid vesicles: (i) vesicles containing biotinylated lipids are coupled together with streptavidin, (ii) bridging attraction is exploited by adding cationic polymers (polylysine) to negatively charged vesicles, and (iii) temperature as a control parameter is used for the aggregation of vesicles mixed with a thermo-sensitive surfactant. While each strategy has its own advantages and disadvantages for vesicle pair formation, the latter strategy additionally shows reversible limited aggregation: above the LCST of pNIPAm, vesicle pairs are formed, while below the LCST, single vesicles prevail. Mixing protocols were assessed by dynamic and static light scattering as well as fluorescence correlation spectroscopy to determine under which conditions vesicle pairs dominate the aggregate size distribution. We have strong indications that without subsequent perturbation, the individual vesicles remain intact and no fusion or leakage between vesicles occurs after vesicle pairs have formed.