The Properties of the Mucus Barrier, a Unique Gel–How Can Nanoparticles Cross It?

Pearson, Jeffrey P.; Chater, Peter I.; Wilcox, Matthew

doi:10.4155/tde-2015-0002

Cited by 58 publications

(64 citation statements)

References 103 publications

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“…22 In particular the only gel-forming protein of intestinal mucus is MUC2, whose concentration is about 60 mg mL À1 in physiological conditions. 41 It displays a linear structure with a variable number of tandem repeats (VNTR). They consist of sequential replicates of amino acid sequences unique to each mucin and enriched in serine, threonine, and proline amino acid residues (Fig.…”

Section: The Relevance Of the Complexity Of Intestinal Mucusmentioning

confidence: 99%

“…4), MUC2 undergoes a sweeping increase of the molecular weight (up to 5 MDa) thanks to intense O-glycosylation rate (between 50-90%). 22,35,41 The presence of these branched structures is a key priority for an in vitro model of intestinal mucus, as it regulates microbial adhesion and hostile activities, and provides the oligosaccharideenriched environment for microbiota metabolism. [44][45][46] Intestinal mucus also contains lipids, cellular debris, DNA and other proteins.…”

Section: The Relevance Of the Complexity Of Intestinal Mucusmentioning

confidence: 99%

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Towards bioinspiredin vitromodels of intestinal mucus

et al. 2019

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Section: The Relevance Of the Complexity Of Intestinal Mucusmentioning

confidence: 99%

Section: The Relevance Of the Complexity Of Intestinal Mucusmentioning

confidence: 99%

Towards bioinspiredin vitromodels of intestinal mucus

et al. 2019

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“… 4 However despite its clear importance and widespread presence in higher organisms, the mechanisms of mucus production and its functionality are still largely unknown, except in the case of the human MUC2 gene product. 5 A more comprehensive understanding of the chemical and physical properties of mucus might suggest novel antimicrobial strategies for clinical application.…”

Section: Introductionmentioning

confidence: 99%

“…While functionally conserved, mucin glycoproteins are structurally complex 43 and separated into secreted soluble, secreted gel-forming and membrane-bound / transmembrane mucins. 5 , 45 Multiple transmembrane mucins have now been identified. 7 , 53 , 54 They are thought to be involved in cellular signalling 26 and on the airway surface, for example, they are used to create a size exclusion barrier.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary conservation of the antimicrobial function of mucus: a first defence against infection

Bakshani

Morales-García

Althaus

et al. 2018

npj Biofilms Microbiomes

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110

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Mucus layers often provide a unique and multi-functional hydrogel interface between the epithelial cells of organisms and their external environment. Mucus has exceptional properties including elasticity, changeable rheology and an ability to self-repair by re-annealing, and is therefore an ideal medium for trapping and immobilising pathogens and serving as a barrier to microbial infection. The ability to produce a functional surface mucosa was an important evolutionary step, which evolved first in the Cnidaria, which includes corals, and the Ctenophora. This allowed the exclusion of non-commensal microbes and the subsequent development of the mucus-lined digestive cavity seen in higher metazoans. The fundamental architecture of the constituent glycoprotein mucins is also evolutionarily conserved. Although an understanding of the biochemical interactions between bacteria and the mucus layer are important to the goal of developing new antimicrobial strategies, they remain relatively poorly understood. This review summarises the physicochemical properties and evolutionary importance of mucus, which make it so successful in the prevention of bacterial infection. In addition, the strategies developed by bacteria to counteract the mucus layer are also explored.

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“…Luminal acid is therefore neutralised before it reaches the mucosal cells [ 3 ]. Whilst permeable to low molecular weight solutes [ 32 ], the gel is impermeable to larger molecules such as pepsin, microbes [ 33 ] and certain viruses such as human papilloma virus and Merkel cell polyomavirus which are prevented from reaching the underlying epithelial cells [ 34 ]. Pepsin however acts on the luminal surface of the gel and hydrolyses polymeric mucins, liberating degraded mucin subunits into the gastric lumen and causing a complete change in the properties of the gel from an ‘elastic’ (semi-solid) state to ‘viscous’ (liquid) state [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Mucus and Mucins: do they have a role in the inhibition of the human immunodeficiency virus?

Mall

Habte

Mthembu

et al. 2017

Virol J

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BackgroundMucins are large O-linked glycosylated proteins which give mucus their gel-forming properties. There are indications that mucus and mucins in saliva, breast milk and in the cervical plug inhibit the human immunodeficiency virus (HIV-1) in an in vitro assay.Main body of abstractCrude mucus gels form continuous layers on the epithelial surfaces of the major internal tracts of the body and protect these epithelial surfaces against aggressive luminal factors such as hydrochloric acid and pepsin proteolysis in the stomach lumen, the movement of hard faecal pellets in the colon at high pressure, the effects of shear against the vaginal epithelium during intercourse and the presence of foreign substances in the respiratory airways. Tumour-associated epitopes on mucins make them suitable as immune-targets on malignant epithelial cells, rendering mucins important as diagnostic and prognostic markers for various diseases, even influencing the design of mucin-based vaccines.Sub-Saharan Africa has the highest prevalence of HIV-AIDS in the world. The main points of viral transmission are via the vaginal epithelium during sexual intercourse and mother-to-child transmission during breast-feeding. There have been many studies showing that several body fluids have components that prevent the transmission of HIV-1 from infected to non-infected persons through various forms of contact.Crude saliva and its purified mucins, MUC5B and MUC7, and the purified mucins from breast milk, MUC1 and MUC4 and pregnancy plug cervical mucus (MUC2, MUC5AC, MUC5B and MUC6), inhibit HIV-1 in an in vitro assay. There are conflicting reports of whether crude breast-milk inhibits HIV-1 in an in vitro assay. However studies with a humanised BLT mouse show that breast-milk does inhibit HIV and that breast-feeding is still advisable even amongst HIV-positive women in under-resourced areas, preferably in conjunction with anti-retroviral treatment.ConclusionThese findings raise questions of how such a naturally occurring biological substance such as mucus, with remarkable protective properties of epithelial surfaces against aggressive luminal factors in delicate locations, could be used as a tool in the fight against HIV-AIDS, which has reached epidemic proportions in sub-Saharan Africa.

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The Properties of the Mucus Barrier, a Unique Gel–How Can Nanoparticles Cross It?

Cited by 58 publications

References 103 publications

Towards bioinspiredin vitromodels of intestinal mucus

Towards bioinspiredin vitromodels of intestinal mucus

Evolutionary conservation of the antimicrobial function of mucus: a first defence against infection

Mucus and Mucins: do they have a role in the inhibition of the human immunodeficiency virus?

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