Support is requested to continue physicochemical analyses of the structure and properties of mucins from different sources. Mucins are very high molecular weight glycoproteins that function as viscosity enhancing or gel- forming components of mucous secretions. Our goal is to understand the aspects of mucin structure and intermolecular interactions which control the viscoelastic behavior of mucus under normal and abnormal conditions such as in Cystic Fibrosis where unusually tenacious mucus is formed. Native mucus will be isolated from canine ovine submaxillary glands and compared with human tracheobronchial mucins from healthy (tracheotomy) and cystic fibrosis patients in the Cystic Fibrosis Center at this University. We will also carry out studies on mucins extracted from cultures of a goblet cell line. Mucin structure and association will be characterized in terms of molecular weights and molecular sizes for laser light scattering. Rheological characterization of concentrated mucin solutions and gels will be carried out by controlled strain and controlled stress rheometry. The latter method is a new addition to our methodology and is particularly suited for analysis of weak gels where application of strain may destroy fragile network structures. By contrasting the behavior of normal and modified mucins (e.g. those from which sugars have been removed) in various ionic media (e.g. Na+ c.f. Ca++), and by investigating the influence on gelation of molecular sub-fragments of mucins (e.g. oligosaccharide side-chains (alditols) and 'linker' protein) we will elucidate the role of intramolecular interactions on mucin rheology. Finally, since evidence suggests that bacterial alginates may have an adhesive interaction with mucins, we propose to investigate the rheological consequences of such interactions which may be relevant to mucus disfunction in CF and bronchitis.
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