Special SEMS seminar: Viscoelasticity of Airway Mucus
Professor Gerard Fuller, Fletcher Jones Professor in the School of Engineering (Stanford)
Date: Thursday 6 April 2023 15:00 - 16:00
Location: Queens Building: QB-210
Gerald Fuller is the Fletcher Jones Professor of Chemical Engineering at Stanford University. He joined Stanford in 1980 following his graduate work at Caltech where he acquired his MS and PhD degrees. His undergraduate education was obtained at the University of Calgary, Canada. Professor Fuller's interests lie in studies of rheology and interfacial fluid mechanics. His work has been recognised by receipt of the Bingham Medal of The Society of Rheology, membership in the National Academy of Engineering, election to the American Academy of Arts and Science, and honorary doctorates from the Universities of Crete, Greece, and Leuven, Belgium. He presently serves as the General Secretary to the International Committee on Rheology.
Mucus that lines the lungs acts as the primary defence against inhaled foreign particles and infectious agents by trapping the invaders and preventing them from penetrating the cell layer. Effective mucus clearance, and thus removal of the trapped invaders, is vital for healthy airway function. Asthma is a chronic inflammatory disorder that results in mucus hypersecretion. Over time, this chronic lung inflammation and mucus accumulation can lead to mucus plug formation in the airway, a primary cause of death in patients with asthma. Inflammatory cytokine IL-13, a major mediator of asthma, induces mucin MUC5AC secretion. While increased concentration of MUC5AC has been shown to inhibit mucociliary clearance, the mechanism of mucus transport impairment remains unclear. 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 situvia magnetic microrheology. Human airway epithelial cells (HAECs) are grown in 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 layer. We apply and remove a magnetic force and track microwire displacement to determine the compliance and viscosity of healthy and IL-13 stimulated 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 rheological measurements. 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.