Browsing by Author "McLean, KM"

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    The interaction of cubosomes with supported phospholipid bilayers using neutron reflectometry and QCM-D
    (Royal Society of Chemistry, 2011-09-21) Shen, HH; Hartley, PG; James, M; Nelson, A; Defendi, H; McLean, KM
    We present the results of a study of the interaction of lyotropic liquid crystalline dispersions with supported lipid bilayers based on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) using a quartz crystal microbalance with dissipation monitoring (QCM-D) and neutron reflectometry (NR). We investigated two types of phytantriol-based cubosome formulations, with subtly different internal nanostructures, with one formulation incorporating 2.5% of the biological lipid di-palmitoylphosphatidylserine (DPPS). The QCM-D data showed that cubosomes do not directly attach to the silica supporting surface but they can accumulate on the model membrane, confirming that there is an attractive interaction between POPC bilayers and the cubosome formulations. We have further used NR to quantify the amount of cubosomes adsorbed on the supported POPC bilayers and to examine the structural rearrangement of cubosomes on interaction with the supported lipid bilayer. The data show that the DPPS-containing cubosomes accumulate at the bilayer surface continuously for 15 hours. Pure phytantriol cubosomes accumulated over a longer time period (36 hours), but accumulated to a lesser degree overall. Furthermore, NR data revealed lipid exchange and structural rearrangements for both types of cubosomes, however, for the DPPS-containing cubosomes, these processes were greater in magnitude and faster. Confocal microscopy analysis of cubosome interactions with HeLa cells in vitro, showed increased membrane affinity for the DPPS-containing formulations, which were consistent with the NR and QCM-D observations. We interpret these observations as suggesting that membrane accumulation, cellular uptake and cytotoxicity of cubosome formulations are directly related to their DPPS content, and that this may be the result of increased propensity for liquid crystalline structural rearrangement, as postulated previously (H. H. Shen et al., Biomaterials, 2010, 31, 9473).© 2011, Royal Society of Chemistry
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    Targeted detection of phosphatidylserine in biomimetic membranes and in vitro cell systems using annexin V-containing cubosomes
    (Elsevier, 2013-11-01) Shen, HH; Lake, V; Le Brun, AP; James, M; Duff, AP; Peng, Y; McLean, KM; Hartley, PG
    In this work we have formulated Annexin V (ANX) decorated phosphatidylserine containing phytantriol (PSPhy) cubosomes to act as probes for the enhanced detection of apoptotic membranes in both model and in vitro cell systems. Small angle X-ray scattering (SAXS) and cryogenic-transmission electron microscopy (Cryo-TEM) indicated that ANX-containing PSPhy (ANX-PSPhy) cubosomes retain the Pn3m cubic symmetry and cubic phase nanoparticle characteristics of PSPhy cubosomes. The interaction of ANX-PSPhy cubosomes with apoptotic model and cellular membranes was also investigated using both quartz crystal microbalance with dissipation and confocal microscopy which confirmed that ANX-PSPhy cubosomes can selectively bind to apoptotic cells and model membranes. Neutron reflectometry has also been used to show strong binding of ANX-PSPhy cubosomes to a model apoptotic membrane, and in addition reveals changes in both the bilayer structure and in the internal structure of the cubosome in a region adjacent to the membrane as a result of material exchange. This material exchange between cubosome and apoptotic model bilayer was further demonstrated using Cryo-TEM. We have demonstrated that lipid bound protein, in this case Annexin V, can be used to target cubosome systems to biological surfaces in vitro. © 2013, Elsevier Ltd.
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    An x-ray and neutron reflectometry study of 'PEG-like' plasma polymer films
    (The Royal Society, 2012-05-07) Menzies, DJ; Nelson, A; Shen, HH; McLean, KM; Forsythe, JS; Gengenbach, TR; Fong, C; Muir, BW
    Plasma-enhanced chemical vapour-deposited films of di(ethylene glycol) dimethyl ether were analysed by a combination of X-ray photoelectron spectroscopy, atomic force microscopy, quartz crystal microbalance with dissipation monitoring (QCM-D), X-ray and neutron reflectometry (NR). The combination of these techniques enabled a systematic study of the impact of plasma deposition conditions upon resulting film chemistry (empirical formula), mass densities, structure and water solvation, which has been correlated with the films' efficacy against protein fouling. All films were shown to contain substantially less hydrogen than the original monomer and absorb a vast amount of water, which correlated with their mass density profiles. A proportion of the plasma polymer hydrogen atoms were shown to be exchangeable, while QCM-D measurements were inaccurate in detecting associated water in lower power films that contained loosely bound material. The higher protein resistance of the films deposited at a low load power was attributed to its greater chemical and structural similarity to that of poly(ethylene glycol) graft surfaces. These studies demonstrate the utility of using X-ray and NR analysis techniques in furthering the understanding of the chemistry of these films and their interaction with water and proteins. Copyright © The Royal Society 2012.