Comparison of Physicochemical Properties of Native Mucus and Reconstituted Mucin Gels

Abstract

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.

Mucosa‐Mimetic Materials for the Study of Intestinal Homeostasis and Disease

“…Enzymatic degradation can also be prevented by adding protease inhibitors to the sodium chloride buffer used to solubilize the retrieved mucus. [ 53 ]…”

“…Recently hydrogel properties of native mucus and the reconstituted mucin gels were compared. [ 53a ] Different relevant hydrogel features such as structural, mechanical and biochemical properties were assessed by preparing hydrogels from natively purified, commercial and synthetic mucin and compared with native mucus. [ 53a ] Broadly, reconstituted MUC2 hydrogels exhibited similar material properties (rheology, biochemical properties, transport) compared to native intestinal mucus.…”

Clostridioides difficile-mucus interactions encompass shifts in gene expression, metabolism, and biofilm formation

“…Previous work showed that oligosaccharide composition within mucus is altered during CDI, and that C. difficile reduces expression of human MUC2 while preferentially interacting with MUC1 12 . C. difficile also benefits from the cleavage of mucins by specific members of the microbiota 20 There are substantial challenges in obtaining mucus that accurately recapitulates native human mucus in its composition and viscoelasticity 22 , properties likely vital to C. difficile-mucus interactions. Human mucus varies from that of animal models, and the processing of commercial mucins removes important components from native mucus and disrupts its structure 23 .…”

Natural and Engineered Isoforms of the Inflammasome Adaptor ASC Form Noncovalent, pH-Responsive Hydrogels

“…Protein- and peptide-based hydrogels are desirable biomaterials for biomedical applications because of their inherent biodegradability, the potential to incorporate a vast variety of functions, and their capability to respond to stimuli. − Biomedical applications of biological hydrogels include emulating artificial extracellular matrices as scaffolds for tissue engineering, drug delivery by controlled release, biomaterials for wound repair and surgery procedures, biosensors, and imaging. − In addition, reconstituted protein-based hydrogels are used to study the function and properties of biological hydrogels such as mucus . Thus, intensive research and bioengineering efforts are currently being directed to design and produce new protein-based hydrogels with tunable mechanical properties and specific functionalities.…”

“…6−8 In addition, reconstituted protein-based hydrogels are used to study the function and properties of biological hydrogels such as mucus. 9 Thus, intensive research and bioengineering efforts are currently being directed to design and produce new protein-based hydrogels with tunable mechanical properties and specific functionalities.…”