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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033365-06
Application #
2139046
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1986-07-01
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1996-08-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Other Basic Sciences
Type
Schools of Engineering
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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