Phase Separation and Nanodomain Formation in Hybrid Polymer/Lipid Vesicles

Hybrid polymer/lipid large unilamellar vesicles (LUVs) were studied by small angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM). For the first time in hybrid vesicles, evidence for phase separation at the nanoscale was obtained, leading to the formation of stable nanodomains enriched either in lipid or polymer. This stability was allowed by using vesicle-forming copolymer with a membrane thickness close to the lipid bilayer thickness, thereby minimizing the hydrophobic mismatch at the domain periphery. Hybrid giant unilamellar vesicles (GUVs) with the same composition have been previously shown to be unstable and susceptible to fission, suggesting a role of curvature in the stabilization of nanodomains in these structures

Vesicles in ionic liquids

The formation of vesicles from 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) in several room-temperature ionic liquids, namely, 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF(4)), 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF(6)), 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EmimNTf(2)), and N-benzylpyridinium bis(trifluoromethylsulfonyl)imide (BnPyNTf(2)), as well as in a water/BmimBF(4) mixture, was investigated. In pure ionic liquids, observations by staining transmission electron microscopy demonstrated clearly the formation of spherical structures with diameters of 200-400 nm. The morphological characteristics of these vesicles in ionic liquids, in particular, the membrane thicknesses, were first investigated by small-angle neutron scattering measurements. The mean bilayer thickness was found to be similar to 63 +/- 1 angstrom in a deuterated ionic liquid (BnPyNTf(2)-d). This value was similar to that observed in water. The effect of Its on the modification of the phase physical properties of multilamellar vesicles (MLVs) was then investigated by differential scanning calorimetry. In pure IL as in water, DPPC exhibited an endothermic pretransition followed by the main transition. These transition temperatures and the associated enthalpies in ILs were higher than those in water because of a reduction of the electrostatic repulsion between zwitterionic head groups. To better understand the effect of ionic liquid on the formation of multilamellar vesicles, mixtures of BmimBF(4) and water, which are miscible in all proportions, were analyzed (BmimBF(4)/water ratio from 0% to 100%). SANS and DSC experiments demonstrated that the bilayer structure and stability were strongly modified by the IL content. Moreover, matching SANS experiments showed that BmimBF(4) molecules prefer to be located inside the DPPC membrane rather than in water