**5.1 Mucus rheological properties**

Mucus rheology plays a critical role in maintaining respiratory health. Mucins are large, highly glycosylated proteins. The polyanionic nature of mucin stems primarily from sialic acid, sulfate, and carboxyl groups present in these linked oligosaccharides. Beside physical entanglement, cationic calcium ions can act as crosslinkers that condense the mucin matrices inside mucin granules before exocytosis. Upon release, phase transition mainly driven by the Donnan effect triggers the massive decondensation of mucin networks. Hydrogen bonding, hydrophilic and hydrophobic interactions have also been proposed to contribute to the gel properties of mucin The gel characteristics and rheological properties of mucin are critical for the maintainance the integrity of epithelia by trapping bacteria and viruses and for mucociliary clearance (Bansil & Stanley, 1995; Verdugo, 1990).

Mucus is mainly composed of large and heavily glycosylated glycoproteins called mucins. The gel-forming mucins rapidly hydrate after exocytosis and, due to their tangle network properties, anneal with other mucins to form a protective barrier at the airway-surface liquid layer. The mucin gel layer lines the epithelial surface of various organs such as the vaginal tract, eyes, gastric wall and pulmonary lumen. Mucus in the airway of lungs serves as an innate immune defense against inhaled particulates, bacteria and viruses. Maintenance of the airway protection mechanism stems from the delicate balance between normal mucus production, transport and clearance. The mucin polymer network of mucus has a characteristic tangled topology. Since the rheological properties of mucus are governed mainly by the tangle density of mucin polymers, which decreases with the square of the volume of the mucin matrix, the mucin network hydration (degree of swelling) is the most critical factor in determining the rheological properties of mucus. The diffusivity of mucin matrices, which is closely related to mucin viscosity, can be calculated from polymer swelling kinetics. Based on the polymer network theory, polymer diffusivity is inversely proportional to its viscosity (Lodge, 1999). Thus, lower rate of mucin diffusivity is associated with higher viscosity, less dispersed and less transportable mucins that appear to characterize the clinical symptoms of thick mucus accumulation and obstruction commonly found in asthma, COPD and CF 44. (Rogers, 2007).

The clinical manifestation of major respiratory diseases (Rogers & Barnes, 2006; Quinton, 2008) are related to thick mucus.

The relationship between mucin dehydration and defective mucus clearance has been well established (Mall et al., 2004). As a result, the poorly hydrated, highly viscous and less transportable mucus appears to accumulate within airway passages (Randell et al., 2006). Obstruction of airway lumen with viscous mucus is usually accompanied by chronic bacterial infection, inflammation and impaired mucociliary transport.
