(415e) Viscoelasticity of Airway Mucus By Live-Cell Rheometry

Mucus plugs occlude airways to obstruct airflow in cystic fibrosis (CF). These plugs form due to mucus stiffening as a result of dysfunction of the CF transmembrane conductance regulator (CFTR) protein, and studies in human airway epithelial cells (HAECs) show that CF cells autonomously generate this pathologic mucus. To determine how HAECs autonomously generate pathologic mucus and how CF treatments modulate mucus behavior, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted by HAECs under varying conditions. We found that normal HAEC mucus exhibited viscoelastic liquid behavior and mucus secreted by CF HAECs exhibited viscoelastic solid-like behavior. In addition, mucus secreted by CF HAECs treated with the CFTR modulator ETI or the mucolytic dPGS-SH exhibits viscoelastic liquid-like behavior, indicating a recovery of normal rheology. Furthermore, mucus secreted by IL-1β– or IL-13–stimulated HAECs exhibits viscoelastic solid-like behavior. Together, our results show that CF HAECs generated pathologically stiffer mucus compared to normal HAECs which can be restored to healthy-like behavior with ETI or dPGS-SH, and that IL-1β– or IL-13–treated HAECs autonomously generated pathologic mucus.