Rheology of Gastric Mucin Exhibits a pH-Dependent Sol−Gel Transition

Abstract

Gastric mucin, a high molecular weight glycoprotein, is responsible for providing the gel-forming properties and protective function of the gastric mucus layer. Bulk rheology measurements in the linear viscoelastic regime show that gastric mucin undergoes a pH-dependent sol-gel transition from a viscoelastic solution at neutral pH to a soft viscoelastic gel in acidic conditions, with the transition occurring near pH 4. In addition to pH-dependent gelation behavior in this system, further rheological studies under nonlinear deformations reveal shear thinning and an apparent yield stress in this material which are also highly influenced by pH.

Helicobacter pylori moves through mucus by reducing mucin viscoelasticity

“…Although pH remained constant in control samples over the period of incubation, in the presence of H. pylori, the pH rapidly elevated to 7.1 to 7.4. In addition to the measured change in pH, we found that there was also a profound difference in the rheological response of the two samples in a manner that was strikingly consistent with that observed in the pH 4 (gel) and pH 6 (solution) buffered PGM samples previously published (26). Frequency dependent viscoelastic moduli (Fig.…”

“…1B), reveal the characteristic yield stress and ''weak strain overshoot'' as described by Hyun et al (32), in the control sample. However, this behavior has completely vanished in the sample with H. pylori which, like the previously published pH 6 (solution) sample, has a very limited linear response regime below 0.1 Pa (26). Finally, the dramatic loss of viscosity and diminishing of shear thinning behavior because of H. pylori observed in steady shear experiments (Fig.…”

“…Finally, in studies by another group comparing the viscosity of mucus from a small group of infected patients, untreated subjects, and those after eradication, it is contested that H. pylori infection does not reduce the viscosity of gastric mucus (48). However, given the strong correlation with the sharp rise in pH in the presence of H. pylori and the subsequent change in rheology in nearly exact parallel with the pH dependence of every measure of viscoelastic response previously established (26), the results here indicate that the dominant effect of H. pylori on gastric mucin rheology is that due to pH elevation. Small differences in moduli are related to use of HCl which leads to different ionic strength than the buffers used in previous studies (26,49,50).…”

“…In either case, these torque calculations should be treated as rough estimates given that the hydrodynamic drag formulae above do not account for many aspects of the behavior of gastric mucin described in ref. 26, including elasticity, shear thinning, and nonlinear response above a yield stress of Ϸ10 Pa.…”

“…Although previous studies have examined the motility of H. pylori and other bacteria in fluids with varying viscosity (21-25), we are not aware of any experimental studies that indicate the ability of a flagellated prokaryote to swim through a gel with GЈ( ) Ͼ GЈЈ( ). It has been shown however, that gastric mucin, the glycoprotein content of mucus primarily responsible for its viscoelastic response, undergoes a reversible pH-dependent sol-gel transition from a viscous polymer solution to a soft gel as pH is lowered below pH Ϸ 4, and vice versa as the pH is raised (26,27). This feature of mucin is believed to play a crucial role in its protective function in the stomach in that by forming a gel at low pH, it forms a viscoelastic barrier protecting the lining of the stomach from damage by its own acidic secretions and other insults (28).…”