title: Lamellar structures of MUC2-rich mucin: a potential role in governing the barrier and lubricating functions of intestinal mucus.
abstract: Mucus is a ubiquitous feature of mammalian wet epithelial surfaces, where it lubricates and forms a selective barrier that excludes a range of particulates, including pathogens, while hosting a diverse commensal microflora. The major polymeric component of mucus is mucin, a large glycoprotein formed by several MUC gene products, with MUC2 expression dominating intestinal mucus. A satisfactory answer to the question of how these molecules build a dynamic structure capable of playing such a complex role has yet to be found, as recent reports of distinct layers of chemically identical mucin in the colon and anomalously rapid transport of nanoparticles through mucus have emphasized. Here we use atomic force microscopy (AFM) to image a MUC2-rich mucus fraction isolated from pig jejunum. In the freshly isolated mucin fraction, we find direct evidence for trigonally linked structures, and their assembly into lamellar networks with a distribution of pore sizes from 20 to 200 nm. The networks are two-dimensional, with little interaction between lamellae. The existence of persistent cross-links between individual mucin polypeptides is consistent with a non-self-interacting lamellar model for intestinal mucus structure, rather than a physically entangled polymer network. We only observe collapsed entangled structures in purified mucin that has been stored in nonphysiological conditions.
authors.affiliation: School of Pharmacy, University of East Anglia , Norwich Research Park, Norwich, UK. a.round@uea.ac.uk
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Round
authors.forename: Neil M
authors.initials: NM
authors.lastname: Rigby
authors.forename: Angela
authors.initials: A
authors.lastname: Garcia de la Torre
authors.forename: Adam
authors.initials: A
authors.lastname: Macierzanka
authors.forename: E N Clare
authors.initials: EN
authors.lastname: Mills
authors.forename: Alan R
authors.initials: AR
authors.lastname: Mackie
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000378:metabolism*; D007583:Jejunum / Q000737:chemistry; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D015394:Molecular Structure; D055262:Mucin-2 / Q000737:chemistry* / Q000302:isolation & purification; D013552:Swine
chemical_list: D055262:Mucin-2