Physics Colloquium - Moving Mucus from the Outside In

Nature employs entangled polymeric networks for a variety of biological functions. These networks form non-linear, heterogeneous, viscoelastic fluids with rheological properties that are length and force-scale dependent. The complexities of the biophysical properties of these systems require skillful measurements that mimic the underlying biological processes one is seeking to understand. My work is focused on the protective airway surface layer (ASL) that lines the epithelium of the respiratory tract. The two components of the ASL, the pericliary layer (PCL) and mucus layer must act in concert to facilitate effective pathogen removal via mucocilary clearance (MCC). In cystic fibrosis (CF), improper chloride secretion by the cystic fibrosis transmembrane conductance regulator results in sodium hyper-absorption by the airway epithelium that draws water from out of the ASL, resulting in mucus with increased concentration and viscoelastic properties. This pathologically concentrated mucus arrests MCC, collapses the PCL, and promotes increased inflammation and infections that are responsible for the majority of morbidity and mortality in CF patients. My research employs diffusive microbead and nanoscopic rheology, as well as driven macroscopic rheology and micro-magnetic force measurements to understand the biophysical properties of mucus and the forces cilia can impart to the mucus layer to facilitate clearance from the lung. These measurements are paired with biochemical characterizations of the concentration, molecular weight, and interactions of the mucin glycoproteins with the > 1,000 other chemical constituents of the mucus layer to effectively trap and clear inhaled pathogens. This basic science approach to understanding the ASL serves as the foundation for translational studies into airway disease pathogenesis, bacterial biofilm growth and eradication, as well as the efficacy of other therapeutic interventions.