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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033365-03
Application #
3231797
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1986-07-01
Project End
1989-11-30
Budget Start
1988-09-20
Budget End
1989-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Rogunova, M A; Blackwell, J; Jamieson, A M et al. (1997) Effects of lipid on the structure and rheology of gels formed by canine submaxillary mucin. Biorheology 34:295-308
Fuongfuchat, A; Jamieson, A M; Blackwell, J et al. (1996) Rheological studies of the interaction of mucins with alginate and polyacrylate. Carbohydr Res 284:85-99
McCullagh, C M; Gupta, R; Jamieson, A M et al. (1996) Gelation of fractionated canine submaxillary mucin in a chaotropic solvent. Int J Biol Macromol 18:247-53
McCullagh, C M; Jamieson, A M; Blackwell, J et al. (1995) Viscoelastic properties of human tracheobronchial mucin in aqueous solution. Biopolymers 35:149-59
Marquart, M; Jamieson, A M; Blackwell, J et al. (1995) Solvent effects on the viscoelastic behavior of porcine submaxillary mucin. Biorheology 32:431-46
McCullagh, C M; Soby, L M; Jamieson, A M et al. (1992) Viscoelastic behavior of fractionated ovine submaxillary mucins. Biopolymers 32:1665-74
Jamieson, A M; Blackwell, J; Zangrando, D et al. (1991) Quasi-elastic and total intensity light-scattering studies of mucin glycoproteins and cartilage proteoglycans. Biochem Soc Trans 19:493
Harpst, J A; Jamieson, A M; Dawson, J R (1991) Polydispersity and excluded volume effects in sheared DNA fragments. Biophys J 60:513-8
Soby, L M; Jamieson, A M; Blackwell, J et al. (1990) Viscoelastic properties of solutions of ovine submaxillary mucin. Biopolymers 29:1359-66
Gupta, R; Jentoft, N; Jamieson, A M et al. (1990) Structural analysis of purified human tracheobronchial mucins. Biopolymers 29:347-55

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