Abstract
Directional flows of cells have been observed during development in a variety of systems ranging from Drosophila to zebrafish. These flows shape living matter in phenomena involving cell mechanics and regulation of the acto-myosin cytoskeleton and are important for morphogenesis. However, the onset of the observed coherent motion is still poorly understood. Here we identify the inherent coherence length to show that coherence is associated with spontaneous alignments of cell polarity. We use cellular rings of controlled dimensions and live tracking of cellular shapes and motions under various experimental conditions, finding that a tug-of-war between cell polarities within the ring dictates the onset of coherence. In addition, we identify an internally driven constraint set by cellular acto-myosin cables at the inner and outer ring boundaries. As these structures have a high RhoA protein activity, they confine the cells and are essential to ensure coherence. The finding that acto-myosin cables are required to trigger coherence is supported by numerical simulations based on a Vicsek-type model that includes free active boundaries. We quantitatively reproduce coherence onsets. We propose that spontaneous coherent motion results from basic competitions between cell orientations and active cables at boundaries.
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Data availability
All data can be provided upon request to riveline@unistra.fr and laurent.navoret@math.unistra.fr.
Code availability
Python codes can be provided upon request to laurent.navoret@math.unistra.fr.
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Acknowledgements
We thank J. Van Unen and M. Inamdar for discussion and feedback. We also thank A. Honigmann (Biotechnology Center, Technical University Dresden) for kindly sharing the ZO1-GFP MDCK cell line, the Imaging Platform of IGBMC, and the Riveline Laboratory for help and discussions. S.L.V. is supported by the University of Strasbourg and by la Fondation pour la Recherche Médicale. D.R., M.S. and L.N. acknowledge support from Idex Unistra and from the Cell Physics Master at the University of Strasbourg. O.P. and D.R. thank funding from SNSF Sinergia grant CRSII5_183550. This work was also supported by a Research Grant from HFSP (Ref. No: RGP0050/2018) and by a French state fund through the Agence Nationale de la Recherche under the frame programme Investissements d’avenir labelled ANR-10-IDEX-0002-02.
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D.R. conceived and supervised the project. S.L.V. performed experiments and analysed the data with D.R. M.S. and L.N. conceived the theoretical framework and ran numerical simulations in close interactions with D.R. and S.L.V. O.P. provided the FRET biosensor and molecular tools to generate cell lines. D.R. and S.L.V wrote the article with feedback from all co-authors. M.S. and L.N. wrote the mathematical modelling section in the Supplementary Information.
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Nature Physics thanks Guillermo Gomez and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Supplementary Information
Supplementary Figs. 1–18, Table 1 and Discussion.
Supplementary Video 1
1,000 µm MDCK ring in phase contrast. Time in hh:mm.
Supplementary Video 2
300 µm MDCK ring in phase contrast. Time in hh:mm.
Supplementary Video 3
180 µm MDCK ring in phase contrast. Time in hh:mm.
Supplementary Video 4
80 µm MDCK ring in phase contrast. Time in hh:mm.
Supplementary Video 5
MDCK ZO1-GFP 80 µm ring in phase contrast. Time in hh:mm.
Supplementary Video 6
Laser ablation on acto-myosin cable (green—GFP). Ring diameter = 80 µm. Time in mm:ss.
Supplementary Video 7
Lifeact transfected cell within the ring ‘building’ the acto-myosin cable (80 µm). Time in hh:mm. Scale bar, 50 µm.
Supplementary Video 8
Caldesmon transfected cell (green—GFP) migrating outwards the 80 µm ring. Time in hh:mm.
Supplementary Video 9
RhoA FRET biosensor spatiotemporal distribution. Ring diameter = 80 µm. Time in hh:mm.
Supplementary Video 10
80 µm simulation.
Supplementary Video 11
180 µm simulation.
Supplementary Video 12
300 µm simulation.
Supplementary Video 13
1,000 µm simulation.
Supplementary Video 14
Caldesmon simulation. The transfected cell corresponds to the blue particle in the simulation. Ring diameter = 80 µm.
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Lo Vecchio, S., Pertz, O., Szopos, M. et al. Spontaneous rotations in epithelia as an interplay between cell polarity and boundaries. Nat. Phys. 20, 322–331 (2024). https://doi.org/10.1038/s41567-023-02295-x
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DOI: https://doi.org/10.1038/s41567-023-02295-x
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