As part of our studies into how the localization of cell adhesion molecules into lipid rafts may affect cell adhesion, we developed Cu(1), a synthetic copper(iminodiacetate)-capped receptor able to phase separate from fluid phospholipid bilayers. The extent to which Cu(1) clustered into adhesive patches on the surface of vesicles could be controlled by changing vesicle composition. Extensive receptor phase separation significantly enhanced vesicle-vesicle adhesion; only vesicles with adhesive patches (blue fluorescence) adhered to their conjugate histidine-coated vesicles (red fluorescence) to form large vesicle aggregates (shown).
Mannosyl glycolipids with perfluoroalkyl membrane anchors have been synthesised. When inserted into vesicles, these mannosyl lipids either dispersed evenly over the surface or, in the presence of cholesterol, phase-separated into artificial lipid rafts. At 1% mol/mol, the affinity of dispersed mannosyl lipids for Con A was 3-fold weaker than in solution, perhaps reflecting steric blocking by the surface. However increasing membrane loading 5-fold increased Con A affinity by up to 75% and indicated weak intramembrane chelation of Con A. Despite this observation, concentrating the mannosyl lipids into artificial lipid rafts did not significantly improve affinity for Con A. This lack of a cluster glycoside effect was ascribed to lipid congestion inhibiting intra-raft chelation of Con A, and implies that glycolipids located in lipid rafts may not necessarily be preorganised for multivalent binding.
Magnetic nanoparticle-vesicle assemblies embedded within a hydrogel extravesicular matrix have been shown to release their contents in response to a remote magnetic trigger.
Vesicles (liposomes) have been shown to be excellent vehicles for drug delivery, yet assemblies of vesicles (vesicle aggregates) have been used infrequently in this context. However vesicle assemblies have useful properties not available to individual vesicles; their size can cause localisation in specific tissues and they can incorporate more functionality than is possible with individual vesicles. This article reviews progress on controlling the properties of vesicle assemblies in vitro, applications of vesicle assemblies in vivo, and our recent creation of magnetic nanoparticle-vesicle assemblies. The latter assemblies contain vesicles crosslinked by coated Fe3O4 nanoparticles and this inclusion of magnetic functionality makes them magnetically responsive, potentially allowing magnetically-induced contents release. This article describes further studies on the in vitro formation of these magnetic nanoparticle-vesicle assemblies, including the effect of changing magnetic nanoparticle concentration, pH, adhesive lipid structure and bilayer composition. These investigations have led to the development of thermally-sensitive magnetic nanoparticle-vesicle assemblies that release encapsulated methotrexate on warming.
As part of efforts aiming to create biomaterials that mimic tissue, patterned vesicle assemblies composed of phospholipid vesicles cross-linked by magnetic nanoparticles have been developed. Multivalent binding between synthetic adhesive lipids in the vesicle membranes and histidine-coated magnetite nanoparticles resulted in the reversible formation of large nanoparticle/vesicle aggregates. The nanoparticles did not insert into or otherwise disrupt the integrity of the vesicle membrane and the cross-linked vesicles retained encapsulated substances. These vesicle/nanoparticle aggregates could be manipulated by external magnetic fields to form patterned vesicle assemblies; for example, they were compressed to form layered materials reminiscent of tissue or compacted within separate chambers of a microflow cell.
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