pH-dependent conformational change of gastric mucin leads to sol-gel transition

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 indicati ve of intermolecular association, yet there was a steady fall in the measur ed diffusion coefficient with decreasing pH, suggesting an apparent increas e in size. Taken together with the observed rise in depolarized scattering ratio with decreasing pH, these results suggest that gastric mucin undergoe s a conformational change from a random coil at pH greater than or equal to 4 to an anisotropic, extended conformation at pH < 4. The increased bindin g of mucin to hydrophobic fluorescent with decreasing pH indicates that the change to an extended conformation is accompanied by exposure of hydrophob ic binding sites. In concentrated mucin solutions, the structure factor S(q , t) derived from DLS measurements changed from a stretched exponential dec ay at pH 7 to a power-law decay at pH 2, which is characteristic of a sol-g el 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 su fficiently concentrated.