Macroheterogeneities Induced by Disulfide Bond Reduction in Native Mucus

Disulfide bond reducing agents have long been used as therapeutic drugs (mucolytics) for mucus hypersecretions. Breakage of disulfide bridges is known to cause a reduction in the degree of cross-linking, making the mucus more fluid. In addition to the drop in viscoelastic properties, the disulfide breakage is also known to affect the structure of the mucus on both micro- and mesoscale. Despite this knowledge, little is known about the reorganization of the mucus at the macroscopic scale. This contribution explores the effect of the reducing agent, tris(2-carboxyethyl)phosphine hydrochloride (TCEP), on the structure of native porcine gastric mucus. After exposing the mucus to increasing concentrations of TCEP, we measure the macroscopic rheological properties along with its microscopic dynamics. The results obtained show an increase in macroscopic heterogeneity with TCEP, which we attribute to the mucus tendency to phase separate. Furthermore, we examine the soluble fractions of the different reduced mucuses by measuring the size of the suspendable macromolecules. The results indicate that the size remains approximately constant with an increasing TCEP concentration. Our contribution may be important to describe the effects of a disulfide reducing agent on the mucus structure and, consequently, on mucociliary and cough clearance.