Composition and Structure of Mucus

The primary constituents of mucus are glycoproteins and water (~ 95%). Mucus glycoproteins (sialomucins, fucomucins, and sulfomucins) are composed of four to five mucin subunits, each with molecular weight of ~500kDa [138,141]. Subunits are composed of a highly glycosylated protein backbone with nonglycosylated protein ends [141,142]. Subunits are attached at their nonglycosylated regions by disulphide bonds and are cross-linked with other glycoproteins by protein-carbohydrate lectin bonds and carbohydrate-carbohydrate noncovalent bonds [120,141,142]. Several other constituents interact with mucus glycoproteins to form a dense network, including phospholipids, cellular and serum macromolecules, neutrophil-derived DNA and F-actin, alginate, electrolytes, microorganisms, and sloughed cells [142]. Concentrations of various constituents are dependent on the anatomical location as well as the physiological and pathophysiological condition of the mucus donor

[142]. Each of these factors contributes to the unique microstructure of mucus, which should be understood prior to the development of gene vectors capable of passing efficiently through the mucosal barrier. Hydrophobic interactions between mucin polymers cause mucus to form a fine network. In cervical mucus, this network consists of a fine mesh with interfiber spacings of approximately 100 nm within a macroporous mesh of interfiber spacings approximately 500 nm

[143]. A similar network structure has been observed in CF sputum [144] (Fig. 2).

Figure 2 Scanning electron microscopic image of CF sputum, showing the pores in the biopolymer network. Bar = 0.5 mm. (Reprinted from Ref. 144. Courtesy of the American Journal of Respiratory Critical Care Medicine.)
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