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Active mucus–cilia hydrodynamic coupling drives self-organization of human bronchial epithelium
Nature Physics ( IF 17.6 ) Pub Date : 2020-08-10 , DOI: 10.1038/s41567-020-0980-z
Etienne Loiseau , Simon Gsell , Aude Nommick , Charline Jomard , Delphine Gras , Pascal Chanez , Umberto D’Ortona , Laurent Kodjabachian , Julien Favier , Annie Viallat

The respiratory tract is protected by mucus, a complex fluid transported along the epithelial surface by the coordinated beating of millions of microscopic cilia, hence the name of mucociliary clearance. Its impairment is associated with all severe chronic respiratory diseases. Yet, the relationship between ciliary density and the spatial scale of mucus transport, as well as the mechanisms that drive ciliary-beat orientations are much debated. Here, we show on polarized human bronchial epithelia that mucus swirls and circular orientational order of the underlying ciliary beats emerge and grow during ciliogenesis, until a macroscopic mucus transport is achieved for physiological ciliary densities. By establishing that the macroscopic ciliary-beat order is lost and recovered by removing and adding mucus, respectively, we demonstrate that cilia–mucus hydrodynamic interactions govern the collective dynamics of ciliary-beat directions. We propose a two-dimensional model that predicts a phase diagram of mucus transport in accordance with the experiments. This paves the way to a predictive in silico modelling of bronchial mucus transport in health and disease.



中文翻译:

主动粘液-纤毛流体动力耦合驱动人支气管上皮细胞的自组织

呼吸道受到粘液的保护,粘液是通过数百万个纤毛的纤毛协同跳动沿上皮表面运输的复杂流体,因此称为粘膜纤毛清除。其损害与所有严重的慢性呼吸系统疾病有关。然而,纤毛密度与粘液运输的空间尺度之间的关系,以及驱动纤毛节律取向的机制,仍存在很多争议。在这里,我们在极化的人支气管上皮细胞上显示,在纤毛形成过程中,粘液涡旋和基础纤毛节拍的圆形取向顺序出现并生长,直到达到生理纤毛密度的宏观粘液运输。通过确定通过移除和添加粘液分别丢失并恢复了宏观的纤毛拍顺序,我们证明纤毛-粘液的水动力相互作用控制着纤毛节拍方向的集体动力学。我们提出了一个二维模型,根据实验预测了粘液运输的相图。这为健康和疾病中支气管粘液运输的计算机模拟预测铺平了道路。

更新日期:2020-08-10
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