(311h) In-Situ Magnetic Microrheology of Airway Mucus

Mucus that lines the lungs acts as the primary defense against inhaled foreign particles and infectious agents by trapping these invaders and preventing them from penetrating the cell layer below. Effective mucus clearance, and thus removal of the trapped invaders, is vital for healthy airway function. Cystic Fibrosis (CF) is a genetic disease that is characterized by hindered ion transport in airway epithelial cells. As a result, the mucus secreted by these cells becomes dehydrated, forming thick stratified layers. This change in mucus material properties can severely impair mucus clearance, leading to airway obstruction, chronic infection, and inflammatory lung damage. It is well established that CF mucus exhibits viscosities orders of magnitude greater than those of healthy mucus. However, thus far it has not been feasible to measure mucus properties on live cells as it is produced by the epithelial cell layer, neglecting the relationship between the physiological environment and mucus rheology. A new instrument, the “Magnetic Live Cell Rheometer”, recently developed by the Fuller group has been adapted to examine mucus rheology in situ via magnetic microrheology. Human airway epithelial cells (HAECs) are grown in 2D air-liquid interface (ALI) cultures, mimicking the airway surface environment. During rheological experiments, we maintain cells at ALI and use micron scale magnetic wires (microwires) to probe the properties of the mucus as a function of distance from the cell layer. We apply and remove a magnetic force and track microwire displacement to determine the compliance and viscosity of healthy and diseased mucus on the respective HAEC cultures. We then test existing mucoactive drugs designed to reduce the elasticity and viscosity of the mucus layer to establish correlation with clinical response and assess the impact of genetic variants. With this method, we demonstrate the ability to study mucus rheology in a physiologically relevant environment, examine phenotypic differences in mucus rheology, and rapidly test drugs on mucociliary mechanics.