A microfluidic in vitro system for the quantitative study of the stomach mucus barrier function

Li, Leon; Lieleg, Oliver; Jang, Sae; Ribbeck, Katharina; Han, Jongyoon

doi:10.1039/c2lc40161d

Cited by 39 publications

(42 citation statements)

References 42 publications

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“…H. pylori-infected rhesus monkeys and children (aged 3 to 18 years) secreting mucins with weaker H. pylori binding capacity develop infections with higher H. pylori density and more severe gastritis (13,20). Patients with primary Sjogren's syndrome are known to produce fewer mucins and are also reported to present a more severe H. pylori-associated pathology (21). These results indicate the ability of secreted mucins to bind to and transport away H. pylori as a mechanism for protecting the gastric epithelium.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Infection Impairs the Mucin Production Rate and Turnover in the Murine Gastric Mucosa

et al. 2013

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To protect the surface of the stomach, the epithelial cells secrete a mucus layer, which is mainly comprised of the MUC5AC mucin. Further protection is provided by a thick glycocalyx on the apical surface of the epithelial cell, with the cell surface mucin MUC1 as a major component. Here, we investigate the production rate and turnover of newly synthesized mucin in mice and analyze the effects of early colonization and chronic infection with H. pylori. Metabolic incorporation of an azido GalNAc analog (GalNAz) was used as a nonradioactive method to perform pulse experiments in the whole animal. First, the subcellular movement of newly synthesized mucin and mucin turnover was determined in uninfected mice. Based on the time line for mucin transport and dissemination, 2, 6, and 12 h after GalNAz injection was selected to collect the stomachs from mice infected with H. pylori strain SS1 during early colonization (7 days) and chronic infection (90 days). The results demonstrated that the speed from the start of glycosylation to the final destination is faster for the membrane-bound mucin to reach the glycocalyx (2 h) than for the secretory mucins to become secreted into the mucus layer (5 h). Furthermore, infection with H. pylori reduces the rate of mucin turnover and decreases the levels of Muc1. Since H. pylori colonizes this mucus niche, the decreased turnover rate indicates that H. pylori creates a more stable and favorable environment for itself by impairing the defense mechanism for clearing the mucosal surface of pathogens by mucus flow.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Infection Impairs the Mucin Production Rate and Turnover in the Murine Gastric Mucosa

et al. 2013

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“…105 Here, we discuss representative examples that illustrate the importance of various intermolecular forces, as well as several cases showing how modulating gel binding could deliver novel approaches to fighting infections.…”

Section: Interactive Filtersmentioning

confidence: 99%

The particle in the spider's web: transport through biological hydrogels

2017

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Biological hydrogels such as mucus, extracellular matrix, biofilms, and the nuclear pore have diverse functions and compositions, but all act as selectively permeable barriers to the diffusion of particles. Each barrier has a crosslinked polymeric mesh that blocks penetration of large particles such as pathogens, nanotherapeutics, or macromolecules. These polymeric meshes also employ interactive filtering, in which affinity between solutes and the gel matrix controls permeability. Interactive filtering affects the transport of particles of all sizes including peptides, antibiotics, and nanoparticles and in many cases this filtering can be described in terms of the effects of charge and hydrophobicity. The concepts described in this review can guide strategies to exploit or overcome gel barriers, particularly for applications in diagnostics, pharmacology, biomaterials, and drug delivery.

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“…In vitro microfluidic mucus model systems: a) (i) Schematic of gastric mucus on the stomach wall in strongly acidic (pH 1–3) gastric juice (A) and design of microfluidic mucus model system with continuous mucin secretion and a proton concentration gradient (B). Reprinted with permission . Copyright 2012, Royal Society of Chemistry.…”

Section: Advanced Mucoadhesion/penetration Testing Platformsmentioning

confidence: 99%

A Polymer Chemistry Point of View on Mucoadhesion and Mucopenetration

Schattling

Taipaleenmäki

Zhang

et al. 2017

Macromolecular Bioscience

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Although oral is the preferred route of administration of pharmaceutical formulations, the long-standing challenge for medically active compounds to efficiently cross the mucus layer barrier limits its wider applicability. Efforts in nanomedicine to overcome this hurdle consider mucoadhesive and mucopenetrating drug carriers by selectively designing (macromolecular) building blocks. This review highlights and critically discusses recent strategies developed in this context including poly(ethylene glycol)-based modifications, cationic and thiolated polymers, as well as particles with high charge density, zeta-potential shifting ability, or mucolytic properties. The latest advances in ex vivo test platforms are also reviewed.

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A microfluidic in vitro system for the quantitative study of the stomach mucus barrier function

Cited by 39 publications

References 42 publications

Helicobacter pylori Infection Impairs the Mucin Production Rate and Turnover in the Murine Gastric Mucosa

Helicobacter pylori Infection Impairs the Mucin Production Rate and Turnover in the Murine Gastric Mucosa

The particle in the spider's web: transport through biological hydrogels

A Polymer Chemistry Point of View on Mucoadhesion and Mucopenetration

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