Abstract

Motile cilia reside on the surface of the epithelial layer of the lungs and facilitates the clearance of mucus in the airways. Bordering the epithelial layer and surrounding cilia is the periciliary liquid (PCL) that lubricates the epithelial layer. In the present work, we propose a novel approach to study how changes in biomechanics affect the physiological functioning of cilia in healthy subjects and in patients with CF, COPD and primary ciliary dyskinesia (PCD). In particular, we investigate the response of cilia to different local pressure gradient during gaseous exchange. We hypothesize that the airway pressure gradient that occur during inhalation and exhalation may displace mucus and PCL and exert pressure on cilia. Therefore, cilia must be able to withstand the forces created by the airway pressure gradient, otherwise the magnitude of its efficient strokes and its rate of mucociliary clearance would decrease. We develop a computational model of the airways to quantify the effect of airway pressure gradient on cilia dynamics. In the model, cilia are represented as elastic solids, PCL and mucus is represented as fluids with different densities and viscosities. The simulation results show that in diseases such as PCD, where there exist changes in ciliary structure, the airway pressure gradient may affect the effective stroke of cilia and decrease the rate of mucociliary clearance. Simulation results predict that the average stress experienced by cilia varies exponential with the number of cilia shed from CF and COPD airways.

Highlights

  • Mucus clearance in the airways is regulated by carpets of cilia that project out of the epithelial layer

  • Based on the study by Hill et al [29] that showed that external forces imposed on cilia can affect it functioning, we propose that the forces generated from the local pressure gradient may affect cilia dynamics with greater effect occurring at airway branch points

  • We propose a novel approach to study how changes in biomechanical factors affect the physiological functioning of cilia in healthy subjects and in patients with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and primary ciliary dyskinesia

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Summary

Introduction

Mucus clearance in the airways is regulated by carpets of cilia that project out of the epithelial layer. Bordering the epithelial layer and surrounding the cilia is the periciliary liquid (PCL) that lubricates the epithelial layer. The mucus layer is sandwiched between the PCL and the air in the core airways. The PCL and mucus layer are referred to as the airway surface liquid (ASL) [5]. PCL facilitates mucus clearance by providing a favorable environment and lubrication for the beating cilia [6]. Mucus serves as a primary defense mechanism by trapping inhaled infectious and toxic agents

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