(118b) Designer Mucus: Poolable and Tunable Airway Mucus for Biochemical, Biophysical, and Transport Studies

Mucus is the first barrier of defense in the human airway system. It is a biopolymeric gel composed of the gel-forming mucins MUC5B and MUC5AC as well as thousands of other biomacromolecules and tightly regulated ionic and water compositions. As a viscoelastic hydrogel its rheology is finely tuned to facilitate clearance from the airways via the mucociliary escalator. Biochemically, mucus is highly adherent to inhaled particles and pathogens, which are subsequently bound to and cleared with the mucus from the lungs. Pathology – particularly hyperconcentration – of mucus occurs in diseases like chronic bronchitis, asthma, and cystic fibrosis, affecting millions of people worldwide. Viral, bacterial, and particulate evasion of the airway mucus barrier affect millions more.

In our work we exploit the fine tuning of the physiological composition of airway of mucus to generate tunable pools of “stock” mucus from heterogeneous mucus samples obtained from living human airways following intubation as part of routine surgery. We demonstrate that compared to “isotonic” samples (i.e. samples obtained with normal ionic composition) that we have previously characterized, samples that were either dehydrated (i.e. hypertonic, due to air exposure) or diluted (i.e. hypotonic, possibly due to salivary contamination) can be either adjusted or combined into pools having physiological composition. These pooled stocks demonstrate bulk and microrheological properties similar to isotonic ETT mucus and mucus from other, non-airway, sources. The composition of the mucus stock can be altered to increased solids concentration and additional free DNA and other components found in mucus during acute or chronic airway disease to recapitulate the biochemistry and biophysics of sputum (e.g. from patients with cystic fibrosis). Furthermore, these stocks can be used to study particle transport through native, physiologically healthy mucus on the size scale of hazardous particles (e.g. asbestos), bacteria, and virions (approximately 10, 1, and 0.1 µm, respectively). Our results demonstrate the utility of native mucus “engineered” to reflect the physiology of the airway mucus barrier in health and disease.