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

• 成果类型: Article
• 署名作者: Causa, Erika; Das, Debasish; Feriani, Luigi; Kotar, Jurij; Cicuta, Pietro
• 署名单位: University of Cambridge; University of Strathclyde
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13552
• DOI: 10.1073/pnas.2419032122
• 发表日期: 2025-07-15
• 关键词: flow-tagging velocimetry; mucociliary clearance; driven transport; mucus clearance; motile cilia; physiology; frequency; particle; liquid; cells

摘要

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.