Ref HAL: hal-04279663_v1
Ref Arxiv: 2310.16770
Ref. & Cit.: NASA ADS
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Résumé:

Large groups of active cilia collectively beat in a fluid medium as metachronal waves, essential for some microorganisms motility and for flow generation in mucociliary clearance. Several models can predict the emergence of metachronal waves, but what controls the properties of metachronal waves is still unclear. Here, we investigate numerically a simple model for cilia in the presence of noise on regular lattices in one- and two-dimensions. We characterize the wave using spatial correlation and the frequency of collective beating. Our results clearly show that the viscosity of the fluid medium does not affect the wavelength; the activity of the cilia does. These numerical results are supported by a dimensional analysis, which is expected to be robust against the model for active force generation, unless surrounding fluid influences the cilia activity. Interestingly, enhancement of cilia activity increases the wavelength and decreases the beating frequency, keeping the wave velocity almost unchanged. These results might have significance in understanding paramecium locomotion and mucociliary clearance diseases.

Commentaires: 6 pages, 5 figures

Ref HAL: hal-03818676_v1
DOI: 10.1098/rsfs.2022.0028
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Mucus is a viscoelastic aqueous fluid that participates in the protective barrier of many mammals' epithelia. In the airways, together with cilia beating, mucus rheological properties are crucial for lung mucociliary function, and, when impaired, potentially participate in the onset and progression of chronic obstructive pulmonary disease (COPD). Samples of human mucus collected in vivo are inherently contaminated and are thus poorly characterized. Human bronchial epithelium (HBE) cultures, differentiated from primary cells at an air–liquid interface, are highly reliable models to assess non-contaminated mucus. In this paper, the viscoelastic properties of HBE mucus derived from healthy subjects, patients with COPD and from smokers are measured. Hallmarks of shear-thinning and elasticity are obtained at the macroscale, whereas at the microscale mucus appears as a heterogeneous medium showing an almost Newtonian behaviour in some extended regions and an elastic behaviour close to boundaries. In addition, we developed an original method to probe mucus adhesion at the microscopic scale using optical tweezers. The measured adhesion forces and the comparison with mucus-simulants rheology as well as mucus imaging collectively support a structure composed of a network of elastic adhesive filaments with a large mesh size, embedded in a very soft gel.

Ref HAL: hal-03751524_v1
PMID 35954266
DOI: 10.3390/cells11152422
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Background: Chronic Obstructive Pulmonary Disease (COPD), a major cause of mortality and disability, is a complex disease with heterogeneous and ill-understood biological mechanisms. Human induced pluripotent stem cells (hiPSCs) are a promising tool to model human disease, including the impact of genetic susceptibility. Methods: We developed a simple and reliable method for reprogramming peripheral blood mononuclear cells into hiPSCs and to differentiate them into air–liquid interface bronchial epithelium within 45 days. Importantly, this method does not involve any cell sorting step. We reprogrammed blood cells from one healthy control and three patients with very severe COPD. Results: The mean cell purity at the definitive endoderm and ventral anterior foregut endoderm (vAFE) stages was >80%, assessed by quantifying C-X-C Motif Chemokine Receptor 4/SRY-Box Transcription Factor 17 (CXCR4/SOX17) and NK2 Homeobox 1 (NKX2.1) expression, respectively. vAFE cells from all four hiPSC lines differentiated into bronchial epithelium in air–liquid interface conditions, with large zones covered by beating ciliated, basal, goblets, club cells and neuroendocrine cells, as found in vivo. The hiPSC-derived airway epithelium (iALI) from patients with very severe COPD and from the healthy control were undistinguishable. Conclusions: iALI bronchial epithelium is ready for better understanding lung disease pathogenesis and accelerating drug discovery.

Ref HAL: hal-02384626_v1
PMID 31774332
DOI: 10.1165/rcmb.2019-0263LE
WoS: 000499728500020
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Ref HAL: hal-02091961_v1
PMID 30943377
DOI: 10.1165/rcmb.2018-0228OC
WoS: WOS:000488779000015
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7 Citations

Ref HAL: hal-02061766_v1
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The mucociliary function of the bronchial epithelium ensures the continuous clearance of the respiratory system. This function relies on two main elements: mucus properties and cilia beating coordination. We work on high speed optical microscopy videos of Human bronchial epithelium from ALI (Air-liquid interface) cultures. We present here a technique based on the tracking of each cilium and on the spatiotemporal analysis of the obtained trajectories. To relate each cilium to its corresponding cell, a clustering method is used. The spatiotemporal coordination can than be quantified both, inside and in-between ciliated cells. In addition the physical parameters can be mapped to observe the heterogeneity of the cilia activity and compare different pathologies.

Ref HAL: hal-02025486_v1
DOI: 10.3389/fphy.2019.00019
WoS: WOS:000459130800002
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1 Citation
Résumé:

We describe an original method to measure mucus microrheology on human bronchial epithelium culture using optical tweezers. We probed rheology on the whole thickness of mucus above the epithelium and showed that mucus gradually varies in rheological response, from an elastic behavior close to the epithelium to a viscous one far away. Microrheology was also performed on mucus collected on the culture, on ex vivo mucus collected by bronchoscopy, and on another epithelium model. Differences are discussed and are related to mucus heterogeneity, adhesiveness and collection method.