Controlling the Localization of Polymer-Functionalized Nanoparticles in Mixed Lipid/Polymer Membranes

Surface hydrophobicity plays a significant role in controlling the interactions between nanoparticles and lipid membranes. In principle, a nanoparticle can be encapsulated into a liposome, either being incorporated into the hydrophobic bilayer interior or trapped within the aqueous vesicle core. In this paper, we demonstrate the preparation and characterization of polymer-functionalized CdSe NPs, tuning their interaction with mixed lipid/polymer membranes from 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phophocholine and PIB₈₇-<i>b</i>-PEO₁₇ block copolymer by varying their surface hydrophobicity. It is observed that hydrophobic PIB-modified CdSe NPs can be selectively located within polymer domains in a mixed lipid/polymer monolayer at the air/water interface, changing their typical domain morphologies, while amphiphilic PIB-PEO-modified CdSe NPs showed no specific localization in phase-separated lipid/polymer films. In addition, hydrophilic water-soluble CdSe NPs can readily adsorb onto spread monolayers, showing a larger effect on the molecule packing at the air/water interface in the case of pure lipid films compared to mixed monolayers. Furthermore, the incorporation of PIB-modified CdSe NPs into hybrid lipid/polymer GUVs is demonstrated with respect to the prevailing phase state of the hybrid membrane. Monitoring fluorescent-labeled PIB-CdSe NPs embedded into phase-separated vesicles, it is demonstrated that they are enriched in one specific phase, thus probing their selective incorporation into the hydrophobic portion of PIB₈₇-<i>b</i>-PEO₁₇ BCP-rich domains. Thus, the formation of biocompatible hybrid GUVs with selectively incorporated nanoparticles opens a new perspective for subtle engineering of membranes together with their (nano-) phase structure serving as a model system in designing functional nanomaterials for effective nanomedicine or drug delivery

A T-Shaped Amphiphilic Molecule Forms Closed Vesicles in Water and Bicelles in Mixtures with a Membrane Lipid

The T-shaped amphiphilic molecule A6/6 forms a columnar hexagonal liquid-crystalline phase between the crystalline and the isotropic liquid when studied in bulk (Chen et al., 2005). Because of the hydrophilic and flexible oligo­(oxyethylene) side chain terminated by a 1-acylamino-1-deoxy-d-sorbitol moiety attached to a rigid terphenyl core with terminal hexyloxy alkyl chains, it was expected that also formation of lyotropic phases could be possible. We therefore studied the behavior of A6/6 in water and also in mixtures with bilayer-forming phospholipids, such as dipalmitoyl-phosphatidylcholine (DPPC), using differential scanning calorimetry (DSC), transmission electron microscopy (TEM), cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and solid-state nuclear magnetic resonance (ssNMR). DSC showed for the pure A6/6 suspended in water a phase transition at ca. 23 °C. TEM and cryo-TEM showed vesicular as well as layered structures for pure A6/6 in water below and above this phase transition. By atomic force microscopy (AFM), the thickness of the layer was found to be 5–6 nm. This leads to a model for a bilayer formed by A6/6 with the laterally attached polar side chains shielding the hydrophobic layer built up by the terphenyl core with the terminal alkyl chains of the molecules. For DPPC:A6/6 mixtures (10:1), the DSC curves indicated a stabilization of the lamellar gel phase of DPPC. Negative staining TEM and cryo-TEM images showed planar bilayers with hexagonal morphology and diameters between 50 and 200 nm. The hydrodynamic radius of these aggregates in water, investigated by dynamic light scattering (DLS) as a function of time and temperature, did not change indicating a very stable aggregate structure. The findings lead to the proposition of a new bicellar structure formed by A6/6 with DPPC. In this model, the bilayer edges are covered by the T-shaped amphiphilic molecules preventing very effectively the aggregation to larger structures