Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease.

The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway mucin 5AC (MUC5AC) and MUC5B concentrations during spontaneous and experimentally induced chronic obstructive pulmonary disease (COPD) exacerbations.

Forgotten but not gone: Particulate matter as contaminations of mucosal systems.

A decade ago, environmental issues, such as air pollution and the contamination of the oceans with microplastic, were prominently communicated in the media. However, these days, political topics, as well as the ongoing COVID-19 pandemic, have clearly taken over. In spite of this shift in focus regarding media representation, researchers have made progress in evaluating the possible health risks associated with particulate contaminations present in water and air.

Purified mucins in drug delivery research.

One of the main challenges in the field of drug delivery remains the development of strategies to efficiently transport pharmaceuticals across mucus barriers, which regulate the passage and retention of molecules and particles in all luminal spaces of the body. A thorough understanding of the molecular mechanisms, which govern such selective permeability, is key for achieving efficient translocation of drugs and drug carriers. For this purpose, model systems based on purified mucins can contribute valuable information.

Structural Alterations of Mucins Are Associated with Losses in Functionality.

Commercial mucin glycoproteins are routinely used as a model to investigate the broad range of important functions mucins fulfill in our bodies, including lubrication, protection against hostile germs, and the accommodation of a healthy microbiome. Moreover, purified mucins are increasingly selected as building blocks for multifunctional materials, i.e.

Repulsive Backbone-Backbone Interactions Modulate Access to Specific and Unspecific Binding Sites on Surface-Bound Mucins.

Mucin glycoproteins are the matrix-forming key components of mucus, the innate protective barrier protecting us from pathogenic attack. However, this barrier is constantly challenged by mucin-degrading enzymes, which tend to target anionic glycan chains such as sulfate groups and sialic acid residues. Here, we demonstrate that the efficiency of both unspecific and specific binding of small molecules to mucins is reduced when sulfate groups are enzymatically removed from mucins; this is unexpected because neither of the specific mucin-binding partners tested here targets these sulfate motifs on the mucin glycoprotein.

Several Sterilization Strategies Maintain the Functionality of Mucin Glycoproteins.

Mucin glycoproteins, the macromolecular components of mucus, combine a broad range of biomedically important properties. Among those is the ability of mucin solutions to act as excellent lubricants. However, to be able to use purified, endogenous mucin glycoproteins as components of a biomedical product, the mucins need to be sterile; this, in turn, makes it necessary to subject the mucins to quite harsh physical treatments, such as heat exposure, autoclaving, UV-, or γ-irradiation, which might compromise the functionality of the glycoproteins.

Charged glycan residues critically contribute to the adsorption and lubricity of mucins.

In the human body, mucin glycoproteins efficiently reduce friction between tissues and thereby protect the mucosa from mechanical damage. Mucin lubricity is closely related to their molecular structure: it has been demonstrated previously that the hydrophobic termini of mucins critically contribute to their lubricity. If and how intrinsic sources of negative charge in mucins, e.

α-Synuclein Penetrates Mucin Hydrogels Despite Its Mucoadhesive Properties.

Recent research indicates that the progression of Parkinson's disease can start from neurons of the enteric nervous system, which are in close contact with the gastrointestinal epithelium: α-synuclein molecules can be transferred from these epithelial cells in a prion-like fashion to enteric neurons. Thin mucus layers constitute a defense line against the exposure of noninfected cells to potentially harmful α-synuclein species. We show that-despite its mucoadhesive properties-α-synuclein can translocate across mucin hydrogels, and this process is accompanied by structural rearrangements of the mucin molecules within the gel.

Transient binding promotes molecule penetration into mucin hydrogels by enhancing molecular partitioning.

Here, we present a microfluidics chip platform which allows for studying the charge-dependent transport of molecules across the interface of acidic mucin gels. With this setup, we demonstrate a selective accumulation of molecules at the liquid/gel interface of mucin hydrogels that occurs as a function of the molecule charge: this phenomenon is strongly pronounced for cationic molecules, weakly pronounced for anionic molecules and absent for neutral molecules. We suggest that molecular transport into and across the gel depends on two main factors, i.