Mucins and Their Role in Shaping the Functions of Mucus Barriers

Abstract

We review what is currently understood about how the structure of the primary solid component of mucus, the glycoprotein mucin, gives rise to the mechanical and biochemical properties of mucus that are required for it to perform its diverse physiological roles. Macroscale processes such as lubrication require mucus of a certain stiffness and spinnability, which are set by structural features of the mucin network, including the identity and density of cross-links and the degree of glycosylation. At the microscale, these same features affect the mechanical environment experienced by small particles and play a crucial role in establishing an interaction-based filter. Finally, mucin glycans are critical for regulating microbial interactions, serving as receptor binding sites for adhesion, as nutrient sources, and as environmental signals. We conclude by discussing how these structural principles can be used in the design of synthetic mucin-mimetic materials and provide suggestions for directions of future work in this field.

Intestinal Mucosal Barrier Function Restoration in Mice by Maize Diet Containing Enriched Flavan-4-Ols

“…These conclusions were also confirmed by the observation of restored intestinal mucus barrier function and the enhanced intestinal permeability we observed under F+ treatment. The glycoprotein-rich mucus layer enables the mechanical response of the large intestine to external force and serves as the first line of defense against invading bacteria by preventing direct contact from the bacteria to the host epithelium [31]. Compromised mucus barrier function is associated with a wide range of chronic diseases as it allows for the translocation of pathogenic components into the bowel wall and leads to immune system activation.…”

Supercharged Proteins and Polypeptides

“…SCFs to a large extent consist of mucins that are composed of a central polypeptide backbone from which negatively charged oligosaccharides protrude to adopt a bottlebrush structure. The negatively charged sugar moieties are responsible for recruiting water molecules that introduce a lubricous layer when mucins adsorb on biosurfaces . Biolubrication can be impaired through several diseases.…”

Mucopenetrating Zwitterionic Micelles

“…The effective delivery of the payload in oral drug formulations is hindered by several biological barriers, including withstanding the acidic conditions of the stomach and reaching the intestinal epithelium, which is protected by a constant secretion of mucus . Mucus is capable of trapping various types of pathogens via entanglement, hydrophobic interactions, electrostatic interactions and multiple low‐affinity interactions, such as hydrogen bonds . Mucopenetrating carriers employ different strategies to circumvent these interactions .…”