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Peer-reviewedCC BYNature Cell Biology

Tissue rigidity phase transition shapes morphogen gradients

  • Camilla Autorino1,2
  • Diana Khoromskaia3,4,5,6
  • Louise Harari2
  • Elisa Floris7
  • H. Anne F. Booth6
  • Cristina Pallares-Cartes2
  • Vesta Petrasiunaite1,2
  • Michael W. Dorrity2
  • Bernat Corominas‐Murtra8
  • Zena Hadjivasiliou9,10,11
  • Nicoletta I. Petridou12
12 affiliations
  1. 1Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany
  2. 2Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  3. 3Department of Physics and Astronomy, University College London, London, UK
  4. 4Institute for Theoretical Physics, University of Münster, Münster, Germany
  5. 5London Centre for Nanotechnology, University College London, London, UK
  6. 6Mathematical and Physical Biology Laboratory, The Francis Crick Institute, London, UK
  7. 7Department of Biology, University of Graz, Graz, Austria
  8. 8Department of Biology, University of Graz, Graz, Austria. [email protected]
  9. 9Department of Physics and Astronomy, University College London, London, UK. [email protected]
  10. 10London Centre for Nanotechnology, University College London, London, UK. [email protected]
  11. 11Mathematical and Physical Biology Laboratory, The Francis Crick Institute, London, UK. [email protected]
  12. 12Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. [email protected]
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Abstract

During development, local mechanochemical cues within the cell microenvironment are translated into signalling pathways that drive cell fate decisions. Yet, as cells differentiate collectively, how global tissue-level properties shape these instructive cues remains unclear. Here we show that a tissue-scale rigidity transition guides patterning by tuning the length scales and timescales of morphogen signalling. By combining rigidity percolation theory, reaction-diffusion modelling, quantitative imaging and optogenetics in zebrafish, we uncover dynamical global tissue rigidity patterns that actively shape the Nodal morphogen gradient by locally changing its concentration and accelerating its signalling activity. In this self-generated mechanism, Nodal, besides instructing meso-endoderm fate specification, increases cell-cell adhesion strength via regulating planar cell polarity genes. Once the adhesion strength reaches a critical point, it triggers a rigidity transition which, in turn, induces the collapse of tissue porosity. The abrupt tissue reorganization negatively feeds back on Nodal signalling, impacting both its length scales, by restricting Nodal diffusivity, and its timescales, by speeding up the expression of its antagonist Lefty, thereby ensuring timely signal termination and robust patterning. Overall, we uncover a multiscale regulatory mechanism by which positional information and tissue material properties dynamically tune one another.

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Cite

BibTeXRIS
BibTeX
@article{autorino2026tissue,
  title = {{Tissue rigidity phase transition shapes morphogen gradients}},
  author = {Camilla Autorino and Diana Khoromskaia and Louise Harari and Elisa Floris and H. Anne F. Booth and Cristina Pallares-Cartes and Vesta Petrasiunaite and Michael W. Dorrity and Bernat Corominas‐Murtra and Zena Hadjivasiliou and Nicoletta I. Petridou},
  journal = {Nature Cell Biology},
  year = {2026},
  month = may,
  doi = {10.1038/s41556-026-01954-4},
  url = {https://doi.org/10.1038/s41556-026-01954-4},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Tissue rigidity phase transition shapes morphogen gradients
AU  - Camilla Autorino
AU  - Diana Khoromskaia
AU  - Louise Harari
AU  - Elisa Floris
AU  - H. Anne F. Booth
AU  - Cristina Pallares-Cartes
AU  - Vesta Petrasiunaite
AU  - Michael W. Dorrity
AU  - Bernat Corominas‐Murtra
AU  - Zena Hadjivasiliou
AU  - Nicoletta I. Petridou
PY  - 2026
DA  - 2026/05/14
JO  - Nature Cell Biology
DO  - 10.1038/s41556-026-01954-4
UR  - https://doi.org/10.1038/s41556-026-01954-4
AB  - During development, local mechanochemical cues within the cell microenvironment are translated into signalling pathways that drive cell fate decisions. Yet, as cells differentiate collectively, how global tissue-level properties shape these instructive cues remains unclear. Here we show that a tissue-scale rigidity transition guides patterning by tuning the length scales and timescales of morphogen signalling. By combining rigidity percolation theory, reaction-diffusion modelling, quantitative imaging and optogenetics in zebrafish, we uncover dynamical global tissue rigidity patterns that actively shape the Nodal morphogen gradient by locally changing its concentration and accelerating its signalling activity. In this self-generated mechanism, Nodal, besides instructing meso-endoderm fate specification, increases cell-cell adhesion strength via regulating planar cell polarity genes. Once the adhesion strength reaches a critical point, it triggers a rigidity transition which, in turn, induces the collapse of tissue porosity. The abrupt tissue reorganization negatively feeds back on Nodal signalling, impacting both its length scales, by restricting Nodal diffusivity, and its timescales, by speeding up the expression of its antagonist Lefty, thereby ensuring timely signal termination and robust patterning. Overall, we uncover a multiscale regulatory mechanism by which positional information and tissue material properties dynamically tune one another.
SN  - 1465-7392
SN  - 1476-4679
ER  -