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Mucus, composed significantly of glycosylated mucins, is a soft and rheologically complex material that lines respiratory, reproductive, and gastrointestinal tracts in mammals. Mucus may present as a gel, as a highly viscous fluid, or as a viscoelastic fluid. Mucus acts as a barrier to the transport of harmful microbes and inhaled atmospheric pollutants to underlying cellular tissue. Studies on mucin gels have provided critical insights into the chemistry of the gels, their swelling kinetics, and the diffusion and permeability of molecular constituents such as water. The transport and dispersion of micron and sub-micron particles in mucin gels and solutions, however, differs from the motion of small molecules since the much larger tracers may interact with microstructure of the mucin network. Here, using brightfield and fluorescence microscopy, high-speed particle tracking, and passive microrheology, we study the thermally driven stochastic movement of 0.5–5.0 μm tracer particles in 10% mucin solutions at neutral pH, and in 10% mucin mixed with industrially relevant dust; specifically, unmodified limestone rock dust, modified limestone, and crystalline silica. Particle trajectories are used to calculate mean square displacements and the displacement probability distributions; these are then used to assess tracer diffusion and transport. Complex moduli are concomitantly extracted using established microrheology techniques. We find that under the conditions analyzed, the reconstituted mucin behaves as a weak viscoelastic fluid rather than as a viscoelastic gel. For small- to moderately sized tracers with a diameter of lessthan 2 μm, we find that effective diffusion coefficients follow the classical Stokes–Einstein relationship. Tracer diffusivity in dust-laden mucin is surprisingly larger than in bare mucin. Probability distributions of mean squared displacements suggest that heterogeneity, transient trapping, and electrostatic interactions impact dispersion and overall transport, especially for larger tracers. Our results motivate further exploration of physiochemical and rheological mechanisms mediating particle transport in mucin solutions and gels.
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Comparison of Physicochemical Properties of Native Mucus and Reconstituted Mucin Gels
Simulating native mucus with model systems such as gels made from reconstituted mucin or commercially available polymers presents experimental advantages including greater sample availability and reduced inter- and intradonor heterogeneity. Understanding whether these gels reproduce the complex physical and biochemical properties of native mucus at multiple length scales is critical to building relevant experimental models, but few systematic comparisons have been reported. Here, we compared bulk mechanical properties, microstructure, and biochemical responses of mucus from different niches, reconstituted mucin gels (with similar pH and polymer concentrations as native tissues), and commonly used commercially available polymers. To evaluate gel properties across these length scales, we used small-amplitude oscillatory shear, single-particle tracking, and microaffinity chromatography with small analytes. With the exception of human saliva, the mechanical response of mucin gels was qualitatively similar to that of native mucus. The transport behavior of charged peptides through native mucus gels was qualitatively reproduced in gels composed of corresponding isolated mucins. Compared to native mucus, we observed substantial differences in the physicochemical properties of gels reconstituted from commercially available mucins and the substitute carboxymethylcellulose, which is currently used in artificial tear and saliva treatments. Our study highlights the importance of selecting a mucus model system guided by the length scale relevant to the scientific investigation or disease application.
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- Award ID(s):
- 2125118
- PAR ID:
- 10540948
- Publisher / Repository:
- Biomacromolecules
- Date Published:
- Journal Name:
- Biomacromolecules
- Volume:
- 24
- Issue:
- 2
- ISSN:
- 1525-7797
- Page Range / eLocation ID:
- 628 to 639
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.biomac.2c01016
