Modeling and Simulation of Mucus Flow in Human Bronchial Epithelial Cell Cultures - Part I: Idealized Axisymmetric Swirling Flow.

Paula A Vasquez,Erik Palmer,Yuan Jin,David Hill,M Gregory Forest,David Smith

doi:10.1371/journal.pcbi.1004872

Abstract

A multi-mode nonlinear constitutive model for mucus is constructed directly from micro- and macro-rheology experimental data on cell culture mucus, and a numerical algorithm is developed for the culture geometry and idealized cilia driving conditions. This study investigates the roles that mucus rheology, wall effects, and HBE culture geometry play in the development of flow profiles and the shape of the air-mucus interface. Simulations show that viscoelasticity captures normal stress generation in shear leading to a peak in the air-mucus interface at the middle of the culture and a depression at the walls. Linear and nonlinear viscoelastic regimes can be observed in cultures by varying the hurricane radius and mean rotational velocity. The advection-diffusion of a drug concentration dropped at the surface of the mucus flow is simulated as a function of Peclet number.

Highlights

The propulsion of mucus in human airways to the trachea by the collective, coordinated action of cilia, known as mucociliary clearance (MCC), remains an outstanding modeling and computational challenge
A MCC model that allows for quantitative predictions of airway surface liquid (ASL) transport as a function of mucus rheological properties is valuable for detecting compromised MCC and assessing mucolytic-based treatments
The ASL is mainly composed of two concentric, annular layers: the periciliary liquid (PCL) layer bordering the epithelium that surrounds the cilia, forming an active medium with apparent polymer brush-like properties [1]; and, a mucus layer between the PCL and air in the core of airways

Summary

Introduction

The propulsion of mucus in human airways to the trachea by the collective, coordinated action of cilia, known as mucociliary clearance (MCC), remains an outstanding modeling and computational challenge. The ASL is mainly composed of two concentric, annular layers: the periciliary liquid (PCL) layer bordering the epithelium that surrounds the cilia, forming an active medium with apparent polymer brush-like properties [1]; and, a mucus layer between the PCL and air in the core of airways. There is no validated constitutive model capable of recapitulating mucus rheology under diverse, physiological stress and deformation conditions. This gap has hindered studies into the causal relationship between mucus rheology and mucociliary clearance. Important advances have been made in understanding the different physiological, biochemical, and mechanical processes at play in MCC

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