---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19373'
abstract:
- lang: eng
text: Reproducible pattern and form generation during embryogenesis is poorly understood.
Intestinal organoid morphogenesis involves a number of mechanochemical regulators
such as cell-type-specific cytoskeletal forces and osmotically driven lumen volume
changes. It is unclear how these forces are coordinated in time and space to ensure
robust morphogenesis. Here we show how mechanosensitive feedback on cytoskeletal
tension gives rise to morphological bistability in a minimal model of organoid
morphogenesis. In the model, lumen volume changes can impact the epithelial shape
via both direct mechanical and indirect mechanosensitive mechanisms. We find that
both bulged and budded crypt states are possible and dependent on the history
of volume changes. We test key modelling assumptions via biophysical and pharmacological
experiments to demonstrate how bistability can explain experimental observations,
such as the importance of the timing of lumen shrinkage and robustness of the
final morphogenetic state to mechanical perturbations. This suggests that bistability
arising from feedback between cellular tensions and fluid pressure could be a
general mechanism that coordinates multicellular shape changes in developing systems.
acknowledgement: We thank all members of the Hannezo and Liberali groups for fruitful
discussions, as well as C. Schwayer, G. Quintas, L. Capolupo, D. Bruckner and D.
Pinheiro for reading the manuscript. We also thank Y. Wu and X. Wu from the Yang
group for performing experiments in the last rounds of revision and the So group
at the National Institute of Biological Sciences, Beijing, for helping with the
light-sheet time-lapse experiments. This work received funding from the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
programme via grant agreement no. 758617 (to P.L.), Swiss National Foundation (SNF)
(no. POOP3_157531 to P.L.), the ERC under the European Union’s Horizon 2020 research
and innovation programme under grant agreement no. 851288 (to E.H.) and the Austrian
Science Fund (FWF) (no. P 31639 to E.H.). This work was supported by the National
Natural Science Foundation of China via grant no.3247060387 (to Q.Y.) and the Strategic
Priority Research Program of the Chinese Academy of Sciences (no. XDB0820000 to
Q.Y.) . Open access funding provided by Institute of Science and Technology (IST
Austria).
article_number: '078104'
article_processing_charge: Yes (via OA deal)
article_type: original
arxiv: 1
author:
- first_name: Shi-lei
full_name: Xue, Shi-lei
id: 31D2C804-F248-11E8-B48F-1D18A9856A87
last_name: Xue
- first_name: Qiutan
full_name: Yang, Qiutan
last_name: Yang
- first_name: Prisca
full_name: Liberali, Prisca
last_name: Liberali
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Xue S, Yang Q, Liberali P, Hannezo EB. Mechanochemical bistability of intestinal
organoids enables robust morphogenesis. Nature Physics. 2025;21. doi:10.1038/s41567-025-02792-1
apa: Xue, S., Yang, Q., Liberali, P., & Hannezo, E. B. (2025). Mechanochemical
bistability of intestinal organoids enables robust morphogenesis. Nature Physics.
Springer Nature. https://doi.org/10.1038/s41567-025-02792-1
chicago: Xue, Shi-lei, Qiutan Yang, Prisca Liberali, and Edouard B Hannezo. “Mechanochemical
Bistability of Intestinal Organoids Enables Robust Morphogenesis.” Nature Physics.
Springer Nature, 2025. https://doi.org/10.1038/s41567-025-02792-1.
ieee: S. Xue, Q. Yang, P. Liberali, and E. B. Hannezo, “Mechanochemical bistability
of intestinal organoids enables robust morphogenesis,” Nature Physics,
vol. 21. Springer Nature, 2025.
ista: Xue S, Yang Q, Liberali P, Hannezo EB. 2025. Mechanochemical bistability of
intestinal organoids enables robust morphogenesis. Nature Physics. 21, 078104.
mla: Xue, Shi-lei, et al. “Mechanochemical Bistability of Intestinal Organoids Enables
Robust Morphogenesis.” Nature Physics, vol. 21, 078104, Springer Nature,
2025, doi:10.1038/s41567-025-02792-1.
short: S. Xue, Q. Yang, P. Liberali, E.B. Hannezo, Nature Physics 21 (2025).
corr_author: '1'
date_created: 2025-03-09T23:01:28Z
date_published: 2025-02-28T00:00:00Z
date_updated: 2025-09-30T10:47:36Z
day: '28'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.1038/s41567-025-02792-1
ec_funded: 1
external_id:
arxiv:
- '2403.19900'
isi:
- '001434072800001'
pmid:
- '40248571'
file:
- access_level: open_access
checksum: fb5e59be145b95f9851d3d7c9dbb85e6
content_type: application/pdf
creator: dernst
date_created: 2025-08-05T12:12:03Z
date_updated: 2025-08-05T12:12:03Z
file_id: '20129'
file_name: 2025_NaturePhysics_Xue.pdf
file_size: 16302436
relation: main_file
success: 1
file_date_updated: 2025-08-05T12:12:03Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 268294B6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31639
name: Active mechano-chemical description of the cell cytoskeleton
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanochemical bistability of intestinal organoids enables robust morphogenesis
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 21
year: '2025'
...