Mucus clearance is the primary defense mechanism that protects airways from inhaled infectious and toxic agents. In the classical gel-on-liquid mucus clearance model, a mucus gel is propelled on top of a “watery” periciliary layer surrounding the cilia. However, this model fails to explain the formation of a distinct mucus layer in health or why mucus clearance fails in disease. We propose and verified a gel-on-brush model in which the periciliary layer is occupied by membrane-spanning mucins and mucopolysaccharides densely tethered to the airway surface. This brush prevents mucus penetration into the periciliary space and causes mucus to form a distinct layer. The relative osmotic moduli of the mucus and periciliary brush layers explain both the stability of mucus clearance in health and its failure in airway disease. We demonstrated a strong correlation between the extent of the chronic bronchitis disease and the state of hydration of the airway surface layer – mucus concentration and the corresponding osmotic pressure.

We are using these ideas to develop biomarkers and treatment strategies for patients with different airway diseases.

Selected Publications