Novel analytical tools reveal that local synchronization of cilia coincides with tissue-scale metachronal waves in zebrafish multiciliated epithelia
- Norwegian University of Science and Technology, Norway
- TU Dresden, Germany
Abstract
Motile cilia are hair-like cell extensions that beat periodically to generate fluid flow along various epithelial tissues within the body. In dense multiciliated carpets, cilia were shown to exhibit a remarkable coordination of their beat in the form of traveling metachronal waves, a phenomenon which supposedly enhances fluid transport. Yet, how cilia coordinate their regular beat in multiciliated epithelia to move fluids remains insufficiently understood, particularly due to lack of rigorous quantification. We combine experiments, novel analysis tools, and theory to address this knowledge gap. To investigate collective dynamics of cilia, we studied zebrafish multiciliated epithelia in the nose and the brain. We focused mainly on the zebrafish nose, due to its conserved properties with other ciliated tissues and its superior accessibility for non-invasive imaging. We revealed that cilia are synchronized only locally and that the size of local synchronization domains increases with the viscosity of the surrounding medium. Even though synchronization is local only, we observed global patterns of traveling metachronal waves across the zebrafish multiciliated epithelium. Intriguingly, these global wave direction patterns are conserved across individual fish, but different for left and right nose, unveiling a chiral asymmetry of metachronal coordination. To understand the implications of synchronization for fluid pumping, we used a computational model of a regular array of cilia. We found that local metachronal synchronization prevents steric collisions, cilia colliding with each other, and improves fluid pumping in dense cilia carpets, but hardly affects the direction of fluid flow. In conclusion, we show that local synchronization together with tissue-scale cilia alignment coincide and generate metachronal wave patterns in multiciliated epithelia, which enhance their physiological function of fluid pumping.
Data availability
All codes including the dataset of the representative sample shown across figures is published on Mendeley Data with the following DOI 10.17632/th35c5833g.2. Matlab codes for analysis is available on github https://github.com/Jurisch-Yaksi-lab/Ringers-et-alPython packages are available on github to (i) reconstruct 3D curves from orthogonal 2D projections: https://github.com/icemtel/reconstruct3d_opt , (ii) create triangulated surface meshes and solve hydrodynamic Stokes equation: https://github.com/icemtel/stokes, and (iii) study systems of coupled oscillators https://github.com/icemtel/carpet .
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Locally synchronized ciliary domains and tissue-scale cilia alignment underlie global metachronal wave patternsMendeley Data, DOI: 10.17632/th35c5833g.2.
Article and author information
Author details
Benjamin M Friedrich
Nathalie Jurisch-Yaksi
Funding
The Research Council of Norway (326003)
- Christa Ringers
The research Council of Norway (314189)
- Nathalie Jurisch-Yaksi
DFG (FR3429/1-1 and -2)
- Benjamin M Friedrich
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Raymond E Goldstein, University of Cambridge, United Kingdom
Ethics
Animal experimentation: The animal facilities and maintenance of the zebrafish, Danio rerio, were approved by the NFSA (Norwegian Food Safety Authority). All procedures were performed on zebrafish larvae at 4 dpf in accordance with the directive 2010/63/EU of the European Parliament and the Council of the European Union and the Norwegian Food Safety Authorities.
Version history
- Preprint posted: November 23, 2021 (view preprint)
- Received: February 8, 2022
- Accepted: January 25, 2023
- Accepted Manuscript published: January 26, 2023 (version 1)
- Version of Record published: February 20, 2023 (version 2)
Copyright
© 2023, Ringers et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Novel analytical tools reveal that local synchronization of cilia coincides with tissue-scale metachronal waves in zebrafish multiciliated epithelia
eLife 12:e77701.
https://doi.org/10.7554/eLife.77701
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