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

Vasquez, Paula A.; Yuan, Junhua; Palmer, Erik Tracey; Hill, David B.; Forest, M. Gregory

doi:10.1371/journal.pcbi.1004872

Cited by 32 publications

(40 citation statements)

References 51 publications

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“…Multiscale analyses of ciliated tissues not only reveal new tissue-level phenomena, but also enable a quantification of their functional roles in different tissue environments. Such analyses require the integration of empirical and computational approaches for studying cilia function, like those developed in this study, as well as for investigating the particular fluid environment, including air and mucus (47).…”

Section: Discussionmentioning

confidence: 99%

Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome

Nawroth

Guo

Koch

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

107

103

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We show that mucociliary membranes of animal epithelia can create fluid-mechanical microenvironments for the active recruitment of the specific microbiome of the host. In terrestrial vertebrates, these tissues are typically colonized by complex consortia and are inaccessible to observation. Such tissues can be directly examined in aquatic animals, providing valuable opportunities for the analysis of mucociliary activity in relation to bacteria recruitment. Using the squid-vibrio model system, we provide a characterization of the initial engagement of microbial symbionts along ciliated tissues. Specifically, we developed an empirical and theoretical framework to conduct a census of ciliated cell types, create structural maps, and resolve the spatiotemporal flow dynamics. Our multiscale analyses revealed two distinct, highly organized populations of cilia on the host tissues. An array of long cilia (∼25 µm) with metachronal beat creates a flow that focuses bacteria-sized particles, at the exclusion of larger particles, into sheltered zones; there, a field of randomly beating short cilia (∼10 µm) mixes the local fluid environment, which contains host biochemical signals known to prime symbionts for colonization. This cilia-mediated process represents a previously unrecognized mechanism for symbiont recruitment. Each mucociliary surface that recruits a microbiome such as the case described here is likely to have system-specific features. However, all mucociliary surfaces are subject to the same physical and biological constraints that are imposed by the fluid environment and the evolutionary conserved structure of cilia. As such, our study promises to provide insight into universal mechanisms that drive the recruitment of symbiotic partners.cilia | microfluidics | host-bacterial symbiosis | biological fluid mechanics, biofiltration M any eukaryotic cells feature motile cilia, microtubulebased surface actuators that sense and propel the extracellular fluidic environment (1-3). Whereas cilia and cilia-like structures that sort and capture bacteria or particles are common and well-characterized features of aquatic organisms (4-7), in terrestrial animals such as mammals, the internal location of ciliated surfaces has made them difficult to study. A central challenge in internal ciliated mucus membranes, such as those lining the fallopian tube, the Eustachian tube, and the respiratory system (8), is to reconcile the effective clearance of toxic molecules and undesirable microbes with selective engagement of beneficial symbionts. For example, on airway epithelia, the coordinated beat of motile cilia creates a horizontal flow across their tips (9-12), which clears mucus, microorganisms, and debris (Fig. 1A). Disruption of this mucociliary clearance can lead to chronic infection of the airways (13). However, this simple model is incomplete; ciliated airway epithelia not only serve a clearance function, but also provide a habitat and a gateway for coevolved symbionts that play an essential role in the development of the host...

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Section: Discussionmentioning

confidence: 99%

Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome

Nawroth

Guo

Koch

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

107

103

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“…It is usually modeled as a Newtonian fluid. In modeling the ASL, some studies focus on the PCL layer, the mucus layer or both [35][36][37][38]. Different modeling strategies have been devised by researchers working to capture the complex dynamics of mucociliary clearance.…”

Section: Introductionmentioning

confidence: 99%

“…Different modeling strategies have been devised by researchers working to capture the complex dynamics of mucociliary clearance. These models differ mainly in their description of the mucus behavior, some describe the mucus as a Newtonian fluid [35,36,[39][40][41] while others describe it as a non-Newtonian fluid [37,38,[42][43][44][45]. These different models have their perks but they also have limitations, great strides have been made toward modeling mucociliary clearance and it remains an active area of research.…”

Section: Introductionmentioning

confidence: 99%

“…Their model simulated the formation of metachronal waves in rows of pulmonary cilia. Vasquez et al [38] constructed a five-mode Giesekus non-linear viscoelastic constitutive law from micro-and macro-rheology experimental data on cell culture mucus. Their model was able to simulate the shape of air-mucus interface in human bronchial epithelial (HBE) culture.…”

Section: Introductionmentioning

confidence: 99%

“…Most of the existing models have focused on describing mucociliary clearance by prescribing a function to capture the motion of cilia [36,38,46]. Emphasis is usually placed on factors inherent in the mucus and/or cilia including the effect of mucus viscosity, height of cilia, height of mucus and PCL layer, cilia beat frequency and the airway pressure gradient and other biomechanical parameters is usually not considered [40].…”

Section: Introductionmentioning

confidence: 99%

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Airway Pressure Gradient May Decrease the Beating Amplitude of Cilia

George

Pidaparti

2019

Front. Phys.

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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 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 propulsive stroke of cilia and decrease the rate of mucociliary clearance. Simulation results predict that the average stress experienced by cilia varies exponentially with the number of cilia shed from CF and COPD airways.

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