Hybrid polymer/lipid vesicles: Insights on phase separation and dynamics from time-resolved fluorescence and microscopy

Recently, hybrid polymer/lipid vesicles were introduced e.g. for drug delivery comprising bimolecular recognition, and the aim is to blend into a single entity the advantages of both different and well established systems, liposomes and polymersomes (vesicles of pure polymer), allowing a fine tuning of stability, bifunctionality and permeability. A comprehensive study of phase separation and domain formation in Giant Hybrid Unilamellar Vesicles (GHUV) was carried out, using several types of polymers and lipids, considering both architecture (grafted, triblock) and molar mass variations. The micro-domains were directly visualized by confocal imaging using suitable labeled polymers and lipids, and FRET-FLIM was used for the detection of nano-domains below microscopy resolution. The sizes, stability and morphology of the observed phase separation are as predictable, dependent on the lipid/molar fraction, but other factors such as the line tension at the domain boundaries, which is fine tuned by the molar mass and polymer architecture, are ruling factors. The lateral diffusion of lipid within polymer chains was determined by FRAP, and it was concluded that no progressive (intermediate) effect is induced by the lipid, the presence of lipid domains playing a clear role.