Phospholipids are the primary constituent of cell membranes. These amphiphiles contain two hydrophobic fatty acid tails and a hydrophilic polar head group, and when dispersed in aqueous solution they self-assemble into bilayers with the polar head groups facing outwards. These bilayers then close in on themselves to create enclosed spherical assemblies with an interior volume isolated from the exterior aqueous solution; these structures are called vesicles and are simple structural mimics of cells. We aim to transform these vesicles in functional mimics of cells. To do so, we synthesise artificial lipids (receptors) with hydrophobic tags, which anchor into the vesicle bilayer membrane, and molecular recognition motifs in the headgroup: for example metal complexes, sugars or biotin. Furthermore, adding fluorine to the hydrophobic tag gives artificial lipids that phase separate in vesicle membranes, giving adhesive patches (artificial “lipid rafts”) that strengthen molecular recognition.

We aim to quantify the effect of lipid rafts on the multivalent recognition of external ligands. We have shown that adhesive patches can strengthen multivalent molecular recognition, for example shown left is green His-tagged green fluorescent protein adhering to a “raft” on the surface of a 40 µm vesicle. This lead to the discovery that receptor clustering in membranes can strengthen vesicle-vesicle adhesion, mimicking the behaviour of cell adhesion molecules. Nonetheless, the enhancement of multivalent recognition depends upon ligand geometry and the strength of the interaction between the ligand and membrane-bound receptors; strong binding can result in receptor reorganisation within the membrane.

The effect of multivalent binding on the lateral phase separation of adhesive lipids.

Liem, KP; Noble, GT; Flitsch, SL; Webb, SJ.

Faraday Discuss. 2010, 145, 219-233.

The effect of receptor clustering on vesicle-vesicle adhesion.

Mart, RJ; Liem, KP; Wang, X; Webb, SJ.

J. Am. Chem. Soc. 2006, 128, 14462-14463.