Laser light scattering and rheological methods will be used to investigate the structure and interactions of mucins in order to understand the structure-property relationships in mucus gels and fluids such as saliva. This project will expand present work on the submaxillary mucins to investigate the structure and properties of the gel-forming gastric and tracheobronchial mucins, and will study the changes in mucus properties that are characteristic of cystic fibrosis. Our work will be relevant to pulmonary diseases such as bronchitis and asthma, and to several digestive diseases. Specimens of porcine, ovine, and canine submaxillary mucins, porcine gastric mucin, and human and feline tracheobronchial mucin will be supplied by colleagues in the Mucin Core Laboratory of this university. Dynamic and classical light scattering will be used to determine the molecular weights and conformations of purified mucins in solution, in order to identify the molecular subunits and to characterize the aggregation hierarchies. A major emphasis will be to follow changes in the diffusion behavior with increasing concentration, ionic strength, and solvent, so as to identify transitions due to the development of entanglements and non-covalent crosslinks. This work will parallel rheological analysis of the interactions in solution in order to investigate the gelation process for gastric and tracheobronchial mucins at the macroscopic level. Mucins from cystic fibrosis tracheobronchial mucus will be compared with healthy specimens in terms of their molecular weights, aggregation, and gelation, in order to understand the syndrome related changes. The physical chemical and rheological data will be combined with the present and developing knowledge of mucin biochemistry to derive models for the structure and association of mucins in solution and in the gel state.
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