Viscoelastic properties of human tracheobronchial mucin in aqueous solution.

Human tracheobronchial mucin isolated from cystic fibrosis patients (CF HTBM) was purified using a combination of gel filtration and density gradient centrifugation. The resulting mucin was fractionated to reduce polydispersity and to facilitate studies of the molecular weight dependence of mucin viscoelasticity in concentrated solution. The viscoelastic properties of CF HTBM were examined in distilled water, 0.1M salt solutions and chaotropic solvents. In controlled strain experiments (strain > or = 5%) with increasing mucin concentration, a crossover from sol to gel behavior is observed. The gel strength, as measured by the magnitude of the storage modulus at comparable mucin concentrations, is greatest for distilled water, intermediate for 0.1M NaCl, and lowest for 6M GdnHCl. In distilled water, high molecular weight mucin undergoes a sol-gel transition at approximately 12 mg/mL, and shows evidence of a plateau modulus at higher concentrations. The storage and loss moduli of concentrated high molecular weight fractions in 6M GdnHCl exhibit a power law dependence on frequency typical of weak gels near the sol-gel transition at 20 mg/mL. Similar rheology is observed in 0.1M NaCl and 0.091M NaCl/3 mM CaCl2, but with evidence for additional weak associations at low frequency. The power law exponent in these systems is 0.70 +/- 0.02, in good agreement with prediction for networks formed by a percolation mechanism. Low molecular weight fractions in these solvents exhibit a fluid-like viscoelastic response. However, low molecular weight mucin in distilled water shows a strain-dependent increase in elasticity at low frequency indicative of weak intermolecular associations. Comparison of the rheological behavior of CF HTBM with our earlier studies of ovine submaxillary mucin lends support to the idea that carbohydrate side-chain interactions are important in the gelation mechanism of mucins.