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纤毛动力学对人呼吸道上皮细胞周纤毛层的穿透形成了动态屏障。

Cilia dynamics create a dynamic barrier to penetration of the periciliary layer in human airway epithelia.

作者信息

Causa Erika, Das Debasish, Feriani Luigi, Kotar Jurij, Cicuta Pietro

机构信息

Department of Physics, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, United Kingdom.

Department of Mathematics and Statistics, University of Strathclyde, Glasgow G1 1XH, United Kingdom.

出版信息

Proc Natl Acad Sci U S A. 2025 Jul 15;122(28):e2419032122. doi: 10.1073/pnas.2419032122. Epub 2025 Jul 11.

Abstract

The ciliated epithelium of the human respiratory tract is covered by the airway surface liquid, a protective fluid consisting of two layers: the periciliary layer (PCL), where motile cilia reside and generate fluid flow, and an overlying mucus layer. The complex structure and stratified nature of the PCL complicate both the prediction and quantification of fluid flow at the scale of individual or small groups of cilia, making it difficult to connect microscopic flows to macroscopic clearance. To tackle this challenge, we developed a methodology that involves "uncaging" a fluorescent compound to trace the flow field within the PCL. Fluorescence is activated at micrometric spots within the cilia layer, and displacement vectors and diffusion are recorded using high-speed video. Our experiments reveal a complex fluid transport pattern, with displacement velocity along the epithelial surface varying due to a nonuniform vertical flow field. Additionally, we observed that cilia expel fluid at their tips, a mechanism likely aimed at preventing pathogen access to the epithelium. Simulations, where cilia are modeled as arrays of rigid rods with length asymmetry, support these findings and offer insights into the dynamics of fluid transport in the respiratory tract and the critical role of cilia coordination.

摘要

人类呼吸道的纤毛上皮被气道表面液体覆盖,这是一种由两层组成的保护液:纤毛周围层(PCL),活动纤毛位于此处并产生流体流动,以及覆盖其上的黏液层。PCL的复杂结构和分层性质使得在单个或小群纤毛尺度上预测和量化流体流动变得复杂,难以将微观流动与宏观清除联系起来。为应对这一挑战,我们开发了一种方法,该方法涉及“解开”一种荧光化合物以追踪PCL内的流场。荧光在纤毛层内的微米级斑点处被激活,并使用高速视频记录位移矢量和扩散情况。我们的实验揭示了一种复杂的流体传输模式,由于垂直流场不均匀,沿上皮表面的位移速度会发生变化。此外,我们观察到纤毛在其尖端排出液体,这一机制可能旨在防止病原体接触上皮。将纤毛建模为具有长度不对称性的刚性杆阵列的模拟支持了这些发现,并为呼吸道中流体传输的动力学以及纤毛协调的关键作用提供了见解。

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