Abstract
We present dynamic light scattering (DLS) and hydrophobic dye-binding data in an effort to elucidate a molecular mechanism for the ability of gastric mucin to form a gel at low pH, which is crucial to the barrier function of gastric mucus. DLS measurements of dilute mucin solutions were not indicative of intermolecular association, yet there was a steady fall in the measured diffusion coefficient with decreasing pH, suggesting an apparent increase in size. Taken together with the observed rise in depolarized scattering ratio with decreasing pH, these results suggest that gastric mucin undergoes a conformational change from a random coil at pH >/= 4 to an anisotropic, extended conformation at pH < 4. The increased binding of mucin to hydrophobic fluorescent with decreasing pH indicates that the change to an extended conformation is accompanied by exposure of hydrophobic binding sites. In concentrated mucin solutions, the structure factor S(q, t) derived from DLS measurements changed from a stretched exponential decay at pH 7 to a power-law decay at pH 2, which is characteristic of a sol-gel transition. We propose that the conformational change facilitates cross-links among mucin macromolecules through hydrophobic interactions at low pH, which in turn leads to a sol-gel transition when the mucin solution is sufficiently concentrated.
Full Text
The Full Text of this article is available as a PDF (225.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adam M, Delsanti M, Munch JP, Durand D. Dynamical studies of polymeric cluster solutions obtained near the gelation threshold: Glasslike behavior. Phys Rev Lett. 1988 Aug 8;61(6):706–709. doi: 10.1103/PhysRevLett.61.706. [DOI] [PubMed] [Google Scholar]
- Afdhal N. H., Niu N., Nunes D. P., Bansil R., Cao X. X., Gantz D., Small D. M., Offner G. D. Mucin-vesicle interactions in model bile: evidence for vesicle aggregation and fusion before cholesterol crystal formation. Hepatology. 1995 Sep;22(3):856–865. [PubMed] [Google Scholar]
- Allen A., Garner A. Mucus and bicarbonate secretion in the stomach and their possible role in mucosal protection. Gut. 1980 Mar;21(3):249–262. doi: 10.1136/gut.21.3.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bansil R., Stanley E., LaMont J. T. Mucin biophysics. Annu Rev Physiol. 1995;57:635–657. doi: 10.1146/annurev.ph.57.030195.003223. [DOI] [PubMed] [Google Scholar]
- Bhaskar K. R., Garik P., Turner B. S., Bradley J. D., Bansil R., Stanley H. E., LaMont J. T. Viscous fingering of HCl through gastric mucin. Nature. 1992 Dec 3;360(6403):458–461. doi: 10.1038/360458a0. [DOI] [PubMed] [Google Scholar]
- Bhaskar K. R., Gong D. H., Bansil R., Pajevic S., Hamilton J. A., Turner B. S., LaMont J. T. Profound increase in viscosity and aggregation of pig gastric mucin at low pH. Am J Physiol. 1991 Nov;261(5 Pt 1):G827–G832. doi: 10.1152/ajpgi.1991.261.5.G827. [DOI] [PubMed] [Google Scholar]
- Carlstedt I., Lindgren H., Sheehan J. K. The macromolecular structure of human cervical-mucus glycoproteins. Studies on fragments obtained after reduction of disulphide bridges and after subsequent trypsin digestion. Biochem J. 1983 Aug 1;213(2):427–435. doi: 10.1042/bj2130427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gong D. H., Turner B., Bhaskar K. R., Lamont J. T. Lipid binding to gastric mucin: protective effect against oxygen radicals. Am J Physiol. 1990 Oct;259(4 Pt 1):G681–G686. doi: 10.1152/ajpgi.1990.259.4.G681. [DOI] [PubMed] [Google Scholar]
- HEATLEY N. G. Mucosubstance as a barrier to diffusion. Gastroenterology. 1959 Sep;37:313–317. [PubMed] [Google Scholar]
- HOLLANDER F. The two-component mucous barrier; its activity in protecting the gastroduodenal mucosa against peptic ulceration. AMA Arch Intern Med. 1954 Jan;93(1):107–120. doi: 10.1001/archinte.1954.00240250117009. [DOI] [PubMed] [Google Scholar]
- Holm L., Flemström G. Microscopy of acid transport at the gastric surface in vivo. J Intern Med Suppl. 1990;732:91–95. doi: 10.1111/j.1365-2796.1990.tb01478.x. [DOI] [PubMed] [Google Scholar]
- Horváth V, V, Vicsek T, Kertész J. Viscous fingering with imposed uniaxial anisotropy. Phys Rev A Gen Phys. 1987 Mar 1;35(5):2353–2356. doi: 10.1103/physreva.35.2353. [DOI] [PubMed] [Google Scholar]
- Martin JE, Wilcoxon J, Odinek J. Decay of density fluctuations in gels. Phys Rev A. 1991 Jan 15;43(2):858–872. doi: 10.1103/physreva.43.858. [DOI] [PubMed] [Google Scholar]
- Martin JE, Wilcoxon JP. Critical dynamics of the sol-gel transition. Phys Rev Lett. 1988 Jul 18;61(3):373–376. doi: 10.1103/PhysRevLett.61.373. [DOI] [PubMed] [Google Scholar]
- Nunes D. P., Keates A. C., Afdhal N. H., Offner G. D. Bovine gall-bladder mucin contains two distinct tandem repeating sequences: evidence for scavenger receptor cysteine-rich repeats. Biochem J. 1995 Aug 15;310(Pt 1):41–48. doi: 10.1042/bj3100041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfeiffer C. J. Experimental analysis of hydrogen ion diffusion in gastrointestinal mucus glycoprotein. Am J Physiol. 1981 Feb;240(2):G176–G182. doi: 10.1152/ajpgi.1981.240.2.G176. [DOI] [PubMed] [Google Scholar]
- Ren SZ, Shi WF, Zhang WB, Sorensen CM. Anomalous diffusion in aqueous solutions of gelatin. Phys Rev A. 1992 Feb 15;45(4):2416–2422. doi: 10.1103/physreva.45.2416. [DOI] [PubMed] [Google Scholar]
- Ren SZ, Sorensen CM. Relaxations in gels: Analogies to alpha and beta relaxations in glasses. Phys Rev Lett. 1993 Mar 15;70(11):1727–1730. doi: 10.1103/PhysRevLett.70.1727. [DOI] [PubMed] [Google Scholar]
- Shogren R., Gerken T. A., Jentoft N. Role of glycosylation on the conformation and chain dimensions of O-linked glycoproteins: light-scattering studies of ovine submaxillary mucin. Biochemistry. 1989 Jun 27;28(13):5525–5536. doi: 10.1021/bi00439a029. [DOI] [PubMed] [Google Scholar]
- Smith B. F., LaMont J. T. Hydrophobic binding properties of bovine gallbladder mucin. J Biol Chem. 1984 Oct 10;259(19):12170–12177. [PubMed] [Google Scholar]
- Strous G. J., Dekker J. Mucin-type glycoproteins. Crit Rev Biochem Mol Biol. 1992;27(1-2):57–92. doi: 10.3109/10409239209082559. [DOI] [PubMed] [Google Scholar]
- Viney C., Huber A. E., Verdugo P. Liquid crystalline order in mucus. Macromolecules. 1993;26(4):852–855. doi: 10.1021/ma00056a044. [DOI] [PubMed] [Google Scholar]
- Williams S. E., Turnberg L. A. Retardation of acid diffusion by pig gastric mucosa: a potential role in mucosal protection. Gastroenterology. 1980 Aug;79(2):299–304. [PubMed] [Google Scholar]