Phase Changes in Mixed Lipid/Polymer Membranes by Multivalent Nanoparticle Recognition

Selective addressing of membrane components in complex membrane mixtures is important for many biological processes. The present paper investigates the recognition between multivalent surface functionalized nanoparticles (NPs) and amphiphilic block copolymers (BCPs), which are successfully incorporated into lipid membranes. The concept involves the supramolecular recognition between hybrid membranes (composed of a mixture of a lipid (DPPC or DOPC), an amphiphilic triazine-functionalized block copolymer TRI-PEO₁₃-<i>b</i>-PIB₈₃ (BCP <b>2</b>), and nonfunctionalized BCPs (PEO₁₇-<i>b</i>-PIB₈₇ BCP <b>1</b>)) with multivalent (water-soluble) nanoparticles able to recognize the triazine end group of the BCP <b>2</b> at the membrane surface via supramolecular hydrogen bonds. CdSe-NPs bearing long PEO₄₇-thymine (THY) polymer chains on their surface specifically interacted with the 2,4-diaminotriazine (TRI) moiety of BCP <b>2</b> embedded within hybrid lipid/BCP mono- or bilayers. Experiments with GUVs from a mixture of DPPC/BCP <b>2</b> confirm selective supramolecular recognition between the THY-functionalized NPs and the TRI-functionalized polymers, finally resulting in the selective removal of BCP <b>2</b> from the hybrid vesicle membrane as proven via facetation of the originally round and smooth vesicles. GUVs (composed of DOPC/BCP <b>2</b>) show that a selective removal of the polymer component from the fluid hybrid membrane results in destruction of hybrid vesicles via membrane rupture. Adsorption experiments with mixed monolayers from lipids with either BCP <b>2</b> or BCP <b>1</b> (nonfunctionalized) reveal that the THY-functionalized NPs specifically recognize BCP <b>2</b> at the air/water interface by inducing significantly higher changes in the surface pressure when compared to monolayers from nonspecifically interacting lipid/BCP <b>1</b> mixtures. Thus, recognition of multivalent NPs with specific membrane components of hybrid lipid/BCP mono- and bilayers proves the selective removal of BCPs from mixed membranes, in turn inducing membrane rupture. Such recognition events display high potential in controlling permeability and fluidity of membranes (e.g., in pharmaceutics)

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