School of Chemistry - Theses

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    Cubic phase lipids as novel biosensing surfaces
    FRASER, SCOTT ( 2011)
    Sub-micron particles, called cubosomes, formed from the fragmentation and steric stabilization of inverse bicontinuous cubic phases (QII) of lipids have a microenvironment reminiscent of biological lipid bilayers, making them promising class of material for a number of applications. The phase behaviour of the amphiphile phytantriol (3,7,11,15-tetramethyl-1,2,3-hexadecanetriol) is well characterised and we describe studies of cubosomes formed from the QII phase of phytantriol/water systems. Cubosomes tailored for specific applications require additional components, which can alter the structure and phase behaviour of the system, for example the incorporation of ligands such as a receptor lipid or protein for biomedical applications. Hence, a study of the effect of additives on the phase behaviour of cubosomes was undertaken. Data obtained using the small-angle X-ray scattering (SAXS) beam line at the Australian Synchrotron showed that addition of non-functional amphiphiles to the matrix of phytantriol/water cubosomes affected the lattice parameter of the cubosomes and, hence, the cubosome microstructure. Oleic acid and monoolein stabilized the Pn3m cubic phase of the cubosomes, whilst CTAB and SDS caused a loss of structure at lower temperatures/molar concentrations of additive. Synchrotron SAXS was also used to investigate the effect of functional additives, the ganglioside receptor, GM1, and the biotinylated phospholipid, bDSPE, on the matrix of the phytantriol/water cubosomes. The results of these studies indicated that both systems would yield stable double diamond Pn3m cubosomes at low – medium molar concentrations of additive. To further investigate the viability of these systems for biomedical and biosensing applications we screened their binding capacity against their natural ligands. Using a combination of enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), and quartz crystal microbalance (QCM) techniques, we showed that GM1 containing cubosomes specifically bind to cholera toxin (CT) with an IC50 of 1.6 nM, which is more potent than any currently available inhibitor. Specific targeting of bDSPE containing cubosomes to avidin-modified surfaces was visualised using cryogenic transmission electron microscopy (cryo-TEM), as was the ability of surface-bound bDSPE cubosomes to specifically bind ligands from solution. Further QCM results demonstrated how bi-functionalised cubosomes, containing GM1 and bDSPE, could be targeted to a surface via one functionality, then sense a secondary ligand via a separate functionality. The results presented in this thesis provide insight into the effect of additives on the phase behaviour of cubosome systems and factors, which affect their potential biomedical and biosensor applications.