Dr Simon Webb

In general, our research interests are in mimicking aspects of biological systems, particularly the functions of biological membranes and the structural characteristics of cells.

Current Projects:

(A) Controlling vesicular adhesion for applications in Bio- and Nanotechnology

Figure 1. A synthetic receptor that can phase separate from liquid ordered phospholipid bilayers.

Figure 2. Fluorescence micrograph of a 40 μm diameter aggregate of red and blue fluorescent vesicles.

We aim to mimic the form and function of tissue by creating structurally defined aggregates of vesicles. The construction of our vesicle aggregates is mediated by synthetic lipids embedded in the vesicle membranes, designed to be mimics of cell adhesion molecules (CAMs).

Initially we showed that multiple weak interactions between poly-L-histidine and Cu-capped membrane-embedded receptors could be used to form vesicle aggregates. We then developed a perfluoroalkyl-pyrene structural motif (Figure 1) and showed that when incorporated into synthetic lipids it enabled them to phase-separate from cholesterol containing phospholipid bilayers. By combining these two discoveries, we created vesicle aggregates in a biomimetic manner, where phase separation of our CAM mimics (Figure 1) into adhesive patches on the surface was required for vesicle aggregation to occur (Figure 2).

(B) Synthetic Ligand Gated Channels

Figure 3. Synthetic Ligand Gated Channels

Cells communicate with each other via the controlled release of chemicals through pores in the cell membrane. We are attempting to reversibly construct pores within the phospholipid bilayer membranes of vesicles by adding compounds (hinges) that will trigger the self-assembly of a pore within the membrane (Figure 3). We have shown that porphy

(C) Developing Surfactants for the crystallisation of Integral Membrane Proteins

Figure 4. Microscopy images of lyotropic liquid crystalline phases viewed through crossed polarizers, for a) monodecyl-D-mannitol surfactant at 78°C; b) monododecyl-D-mannitol surfactant at 58°C

“Integral membrane proteins” (IMPs) perform some of the most fundamental cellular processes, but due to their amphiphilic nature only around 30 integral membrane proteins have had their crystal structures determined. Surfactants must be added to enable them to crystallise, but little is known about the chemical requirements of suitable surfactants. We have synthesised and characterised new classes of surfactants for use in the isolation, purification and crystallization of IMPs. Their potential as IMP crystallising agents was assessed by measuring their lyotropic liquid crystalline behaviour (Figure 4).rins (panels) and metal complexes (hinges) can self-assemble and allow the passage of the fluorescent dye 5/6 CF through vesicle membranes.

(D) Protease Screening on Liquid Crystal Arrays

Figure 5. (a) LC layer only (b) Addition of 0.1 mM tetrapeptide lipid C18H37O(CH2CH2O)8CH2C(O)-[Lys-Phe-Phe-Lys]

We are using changes in the optical properties of thermotropic liquid crystal (LC) coated glass slides to screen the action of unknown proteases on large peptide libraries. The protease-catalysed cleavage of peptidic lipids causes a change in surface activity, which alters the alignment of the LC layer and gives an optical response. A change in brightness when viewed through crossed polarisers (Figure 5) indicates a positive result and signals the protease is specific for that peptide sequence.

(E) Vesicle Films; a new type of biomaterial

Figure 6.  Fluorescence micrograph showing bands of rhodamine-labeled magnetic nanoparticle-vesicle aggregates (pink) and unlabeled magnetic nanoparticle-vesicle aggregates (blue) in a trough on a glass slide.

We are manufacturing of new type of biomaterial, vesicle films, that as a central component of their structure, contain vesicles (simple cell mimics) cross-linked by magnetic nanoparticles. This gives them the physical characteristics of tissue yet also allows them to be manipulated by, and responsive to, external magnetic fields (Figure 6). These vesicle films should have a variety of applications; in mimicking tissue, as anti-bacterial coatings for catheters and for subcutaneous drug delivery.

1. “Magnetic Assembly and Patterning of Vesicle/Nanoparticle Aggregates” K.P. Liem, R.J. Mart, and S.J. Webb, J. Am. Chem. Soc, 2007, 129, 12080-12081.
2. “Vesicle aggregation by multivalent ligands; relating crosslinking ability to surface affinity” X. Wang, R.J. Mart and S.J. Webb, Org. Biomol. Chem. 2007, 5, 2498-2505.
3. “Transmission of Binding Information across Lipid Bilayers” H.P. Dijkstra, J.J. Hutchinson, C.A. Hunter, H. Qin, S. Tomas, S.J. Webb and N.H. Williams, Chem. Eur. J., 2007, 13, 7215-7222.
4. “The Effect of Receptor Clustering on Vesicle-Vesicle Adhesion” R.J. Mart, X. Wang, K.P Liem and S.J. Webb, J. Am. Chem. Soc, 2006, 128, 14462-14463.
5. “Lipid fluorination promotes liquid/liquid immiscibility in phospholipid bilayers”, M. Bayati, K. Greenaway, L. Trembleau and S.J. Webb, Org. Biomol. Chem., 2006, 4, 2399-2407.
6.  “Synthesis and lyotropic phase behavior of novel nonionic surfactants for the crystallization of integral membrane proteins” J. Walton, G.J.T. Tiddy and S.J. Webb, Tetrahedron Lett, 2006, 47, 737-741.
7. “Membrane composition determines the fate of aggregated vesicles” S.J. Webb, L. Trembleau, R.J. Mart and Xi Wang, Org. Biomol. Chem., 2005, 3, 3615 - 3617.
8. “Cooperative Binding at Lipid Bilayer Membrane Surfaces”, E.L. Doyle, C.A. Hunter, H.C. Phillips, S.J. Webb and N.H. Williams, J. Am. Chem. Soc, 2003, 125, 4593-4599.
9. “Transmembrane Signalling” P. Barton, C.A. Hunter, T.J. Potter, S.J. Webb and N.H. Williams, Angew. Chem. Intl. Ed, 2002, 41, 3878-3881.