Giant Vesicles Encapsulating Aqueous Two-Phase Systems: From Phase Diagrams to Membrane Shape Transformations

In this review, we summarize recent studies on giant unilamellar vesicles enclosing aqueous polymer solutions of dextran and poly(ethylene glycol) (PEG), highlighting recent results from our groups. Phase separation occurs for these polymer solutions with concentration above a critical value at room temperature. We introduce approaches used for constructing the phase diagram of such aqueous two-phase system by titration, density and gel permeation chromatography measurements of the coexisting phases. The ultralow interfacial tension of the resulting water-water interface is investigated over a broad concentration range close to the critical point. The scaling exponent of the interfacial tension further away from the critical point agrees well with mean field theory, but close to this point, the behavior disagrees with the Ising value of 1.26. The latter discrepancy arises from the molar mass fractionation of dextran between coexisting phases. Upon encapsulation of the PEG-dextran system into giant vesicles followed by osmotic deflation, the vesicle membrane becomes completely or partially wetted by the aqueous phases, which is controlled by the phase behavior of the polymer mixture and the lipid composition. Deflation leads to a reduction of the vesicle volume and generates excess area of the membrane, which can induce interesting transformations of the vesicle morphology such as vesicle budding. More dramatically, the spontaneous formation of many membrane nanotubes protruding into the interior vesicle compartment reveals a substantial asymmetry and spontaneous curvature of the membrane segments in contact with the PEG-rich phase, arising from the asymmetric adsorption of polymer molecules onto the two leaflets of the bilayers. These membrane nanotubes explore the whole PEG-rich phase for the completely wetted membrane but adhere to the liquid-liquid interface as the membrane becomes partially wetted. Quantitative estimates of the spontaneous curvature are obtained by analyzing different aspects of the tubulated vesicles, which reflect the interplay between aqueous phase separation and spontaneous curvature. The underlying mechanism for the curvature generation is provided by the weak adsorption of PEG onto the lipid bilayers, with a small binding affinity of about 1.6 k_BT per PEG chain. Our study builds a bridge between nanoscopic membrane shapes and membrane-polymer interactions.