# Macroheterogeneities Induced by Disulfide Bond Reduction in Native Mucus

## TL;DR

This paper investigates how reducing disulfide bonds in mucus with TCEP increases macroscopic heterogeneity and may affect mucus clearance mechanisms.

## Contribution

The study reveals new insights into macroscopic structural changes in mucus caused by disulfide bond reduction.

## Key findings

- TCEP increases macroscopic heterogeneity in mucus, suggesting a tendency for phase separation.
- The size of suspendable macromolecules in mucus remains constant despite increasing TCEP concentration.
- Disulfide reduction affects mucus structure at multiple scales, including macroscopic reorganization.

## Abstract

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.