A Dynamic Model of Cystic Fibrosis Airway Epithelium Electrophysiology

Abstract

Modeling the ion and liquid transport dynamics of the Cystic Fibrosis (CF) airway epithelium has the potential to provide valuable insight into the nature of biophysical processes not accessible experimentally We have developed a model that describes key elements of the airway epithelium’s electrophysiology as measured by short-circuit current (Isc) traces obtained under Ussing Chamber (UC) conditions. The model structure uses well established mathematical relations describing the transport of liquid and ions across the epithelium. The model was informed with data measured from primary human bronchial epithelial (HBE) cell cultures harvested from CF and non-CF donors. Fitted trajectories recapitulate experimental data with an average relative error of 3.28%, demonstrating the model’s ability to capture Isc dynamics. Multi-parameter distributions showed significant differences between the predicted ion permeabilities for each population, in accordance with literature trends. This suggests that model-informed parametric descriptions of patient groups could help supplement current experimental protocols, and help identify key dynamic differences relevant to the pathophysiology of CF.