title: A mechanochemical model for auto-regulation of lung airway surface layer volume.
abstract: We develop a proof-of-principle model for auto-regulation of water volume in the lung airway surface layer (ASL) by coupling biochemical kinetics, transient ASL volume, and homeostatic mechanical stresses. The model is based on the hypothesis that ASL volume is sensed through soluble mediators and phasic stresses generated by beating cilia and air drag forces. Model parameters are fit based on the available data on human bronchial epithelial cell cultures. Simulations then demonstrate that homeostatic volume regulation is a natural consequence of the processes described. The model maintains ASL volume within a physiological range that modulates with phasic stress frequency and amplitude. Next, we show that the model successfully reproduces the responses of cell cultures to significant isotonic and hypotonic challenges, and to hypertonic saline, an effective therapy for mucus hydration in cystic fibrosis patients. These results compel an advanced airway hydration model with therapeutic value that will necessitate detailed kinetics of multiple molecular pathways, feedback to ASL viscoelasticity properties, and stress signaling from the ASL to the cilia and epithelial cells.
authors: Department of Mathematics, University of North Carolina, Chapel Hill, NC, USA. gregoryh@unc.edu
authors: Gregory
authors: G
authors: Herschlag
authors: Guilherme J M
authors: GJ
authors: Garcia
authors: Brian
authors: B
authors: Button
authors: Robert
authors: R
authors: Tarran
authors: Brandon
authors: B
authors: Lindley
authors: Benjamin
authors: B
authors: Reinhardt
authors: Timothy C
authors: TC
authors: Elston
authors: M Gregory
authors: MG
authors: Forest
mesh_terms: D001834:Body Water / Q000502:physiology; D002923:Cilia / Q000502:physiology; D004548:Elasticity; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000502:physiology*; D008954:Models, Biological; D009093:Mucus / Q000502:physiology; D020545:Respiratory Mucosa / Q000502:physiology*; D013314:Stress, Mechanical; D014783:Viscosity