Faculty Collaboration Database

A mechanochemical model for auto-regulation of lung airway surface layer volume. J Theor Biol 2013 May 21;325:42-51

Date

02/19/2013

Pubmed ID

23415939

Pubmed Central ID

PMC3631568

DOI

10.1016/j.jtbi.2013.01.023

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.

Author List

Herschlag G, Garcia GJ, Button B, Tarran R, Lindley B, Reinhardt B, Elston TC, Forest MG

Author

Guilherme Garcia PhD Assistant Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Body Water
Cilia
Elasticity
Homeostasis
Humans
Lung
Models, Biological
Mucus
Respiratory Mucosa
Stress, Mechanical
Viscosity