Continuum-kinetic-microscopic model of lung clearance due to core-annular fluid entrainment

Abstract

The human lung is protected against aspirated infectious and toxic agents by a thin liquid layer lining the interior of the airways. This airway surface liquid is a bilayer composed of a viscoelastic mucus layer supported by a fluid film known as the periciliary liquid. The viscoelastic behavior of the mucus layer is principally due to long-chain polymers known as mucins. The airway surface liquid is cleared from the lung by ciliary transport, surface tension gradients, and airflow shear forces. This work presents a multiscale model of the effect of airflow shear forces, as exerted by tidal breathing and cough, upon clearance. The composition of the mucus layer is complex and variable in time. To avoid the restrictions imposed by adopting a viscoelastic flow model of limited validity, a multiscale computational model is introduced in which the continuum-level properties of the airway surface liquid are determined by microscopic simulation of long-chain polymers. A bridge between microscopic and continuum levels is constructed through a kinetic-level probability density function describing polymer chain configurations. The overall multiscale framework is especially suited to biological problems due to the flexibility afforded in specifying microscopic constituents, and examining the effects of various constituents upon overall mucus transport at the continuum scale.

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

“…These numerical models employ either Newtonian fluid assumptions or canonical non-Newtonian constitutive equations to model the mucus layer. Within this class of studies, we note in particular two multiscale models developed by Mitran [ 17 , 23 ]. In one model [ 17 ], internal motor forces within each cilium adapt to local flow conditions guided by a minimization of work hypothesis, leading to cilia synchronization and metachronal wave formation.…”

“…Another study by Mitran [ 23 ] builds a computational platform based on concepts from polymer gel theory, including a distribution of microscopic interactions that up-regulate the rheological properties of mucus. This platform and microscopic dynamics have not been validated with experimental data so the predictions are meant to establish proof-of-principle of the numerical tools.…”

“…We do not address this problem in the current paper. Instead, we draw from previous work [ 21 , 23 ] and treat the PCL as a moving solid boundary, averaging out the scales of the coordinated cilia to study the mean mucus transport features due to a homogeneous dynamic cilia carpet. This idealization affords an axisymmetric reduction to two space dimensions ( Fig 1D ).…”

Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment

“…The upper gel layer, also known as the mucus layer, consists of water, mucins, lactoferrin, and various peptides, and the lower sol or periciliary liquid layer mainly consists of water ( Figure 1 ). The two layers act like a defense barrier known as the “cilia-mucus blanket” [ 18 ]. There is a surfactant layer between the mucus gel and periciliary sol layer, which acts as a lubricant and also facilitates the transfer of energy from beating cilia to mucus [ 19 ].…”

A Macroscopic Model for Simulating the Mucociliary Clearance in a Bronchial Bifurcation: The Role of Surface Tension

“…Recently, Mitran presented an extremely sophisticated submicroscopic finite-element model [21], where the cilia were modeled as deforming solid structures interacting with the surrounding fluid. The same author also presented a work on modeling mucins at a molecular level in order to derive the macroscopic rheological properties of mucus in the respiratory tree [22].…”