Mucins are highly glycosylated molecules with O-linked oligosaccharides arranged in dense patches along the peptide core. Epithelial mucins (PDF, 2.3Mb) coat all moist epithelia. Rich interactions between mucins and bacteria result in the selection of a local flora. Mucus gels also protect from mechanical and chemical injuries. Rich glcosylation and charged oligosaccharides maintain layers of hydration, providing lubrication e.g. during blinking or swallowing.
Oligosaccharides are occupying most of the molecular volume of a mucin. We have shown that human ocular mucins have short oligosaccharides. More recently we sequenced these chains and find low diversity and high sialic acid content1.
We have explored the architecture, adhesion, conformation and gel formation of purified ocular mucins in a long-standing and active collaboration with physicists at the HH Wills Physics Laboratory2-6.
Our latest project focuses on the simultaneous topographic and functional mapping of mucins. A dual cantilever was developed, where each tip can be functionalised, so that different functionalities (e.g. different linkages of sialic acid, epitopes in the peptide core) can be probed in the same scan line. Sarah Baos is measuring unbinding forces (PPT, 824Kb) between anti-mucin or sugar probes and mucin molecules. The latter are either isolated, or in a mucin network, or part of a mucosal gel.
Collaborators: Katharine Evans, Paul Murphy, Heiko Pult, Christine Purslow (CLAER, Cardiff University).
Comfort is a major factor in the success of contact lens wear. We have previously analysed populations of mucins adhering to contact lenses7, 8. Two recent projects have assessed mucins on individual contact lenses (PDF, 1.3Mb) and the correlations between patterns of adhesion and fragmentation and symptoms of contact lens-induced dry eye9 (PDF, 988Kb).
Mucositis is at common and very unpleasant side effects of cancer therapy. The protective and lubricative properties of saliva, suggested that mucins and their associated molecules, trefoil peptides, might be altered in this condition. Fran Verey has analysed these in saliva of children undergoing therapy and healthy children of similar ages. This highlighted considerable differences between adult and child saliva, so Tim Hall is analysing changes in salivary mucins during childhood.