Our work has centred on studying molecular structure and dynamics at wet interfaces under conditions mimicking biological and biomedical applications. We are well established in applying leading physical techniques to access direct information at molecular and cellular levels from various biointerfacial processes. The highlight of our recent work has been to apply spectroscopic ellipsometry (SE) and neutron reflection to reveal protein molecular features underlying surface biocompatibility, a topic highly relevant to biomaterials development, tissue engineering, controlled local drug and gene delivery and medical implant deployment.
We often conduct these research activities in close collaboration with life scientists and medical experts. Within the Biological Physics Group, we place a strong emphasis on seeking integrated approaches between theoreticians, computational experts and experimentalists and try to approach research topics with balanced skills and expertise. Current research topics are:
The in situ structural conformations of antibody molecules immobilised at the solid/solution interface are widely thought to affect their ability to bind antigen from solution, but few techniques have the structural sensitivity to unravel them. In our work neutron reflection has been applied to studying the structure and composition of a monoclonal antibody and its specific recognition by human chorionic gonadotrophin (hCG), a hormonal protein. Our results show that under most physiological mimicking conditions, antibodies adsorb flat-on, with their fragments lying flat on the substrate surface and that the antigen binding capacity decreases with increasing antibody surface packing density. The model system provides an important platform for assessing the effect of surface chemistry and solution environment on antibody immobilisation and bioactivity (see Fig 1, for example).
Study of interactions between biomaterial and vascular cells is highly relevant to the control of cell seeding and tissue growth. In this project, we emphasise the understanding of the mediation of representative ECM proteins on the attachment, spreading and growth of vascular cells. In parallel, the up and down regulations of key proteins excreted by cells are also monitored. Using well-fabricated planar surfaces and polymeric films as model biomaterial, the different biointerfaces are interrogated by a combined approach of biochemical and biophysical techniques. The information so obtained is highly useful towards future model development and growth of 3D tissue constructs.
In collaboration with colleagues from Biocompatibles UK Ltd and Manchester Medical School, we exploit molecular interactions to the benefit of loading bioactive genes into biocompatible surfaces and thin films. We aim at developing the new technology towards the coating of vascular stents. Controlled local drug or gene release could help mediate the local biological environment leading to the healthy integration of the implants. Physical studies using neutron reflection, SANS and spectroscopic ellipsometry help tune nanoporous network and surface chemistry, leading to the effective manipulation of gene loading and release kinetics.
Fig. 2 shows how film thickness and cationic charge density (in CAT%) affects the loading of a FAM-labelled oligodeoxynucleutide loaded in different PC polymers with single (x1) or multiplayer (x3) fabrication.
We apply our extensive expertise in polymer and surfactant research to design short peptide sequences as biomaterials. There are some 20 natural amino acids that are polar (hydrophilic), non-polar (hydrophobic) and charged (positive and negative). They offer almost endless choices for novel peptide surfactant design and synthesis. Neutron reflection and small angle neutron scattering (SANS) are well suited for revealing the nano-structures of these peptides assembled at interfaces and their aggregates formed in bulk solution.
Fig. 3 shows a schematic of a pair of 15-mer peptides forming α-helical configuration via the strong hydrophobic interdigitation of three tryptophans between them. The α-helical backbone is illustrated as a ribbon. W groups are labelled in green, Y in cyan, R in red, and K in blue. The α-helical structure was revealed at the silicon oxide/water interface (J. Am. Chem. Soc. 2004, 126, 8940).