{"corr_author":"1","OA_type":"hybrid","_id":"19373","type":"journal_article","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."}],"article_number":"078104","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41567-025-02792-1"}],"date_updated":"2025-03-10T07:27:30Z","date_created":"2025-03-09T23:01:28Z","publication_identifier":{"eissn":["1745-2481"],"issn":["1745-2473"]},"day":"28","title":"Mechanochemical bistability of intestinal organoids enables robust morphogenesis","status":"public","oa":1,"project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","grant_number":"851288","name":"Design Principles of Branching Morphogenesis"},{"grant_number":"P31639","name":"Active mechano-chemical description of the cell cytoskeleton","call_identifier":"FWF","_id":"268294B6-B435-11E9-9278-68D0E5697425"}],"language":[{"iso":"eng"}],"external_id":{"arxiv":["2403.19900"]},"department":[{"_id":"EdHa"}],"OA_place":"publisher","ec_funded":1,"month":"02","arxiv":1,"author":[{"id":"31D2C804-F248-11E8-B48F-1D18A9856A87","full_name":"Xue, Shi-lei","first_name":"Shi-lei","last_name":"Xue"},{"full_name":"Yang, Qiutan","first_name":"Qiutan","last_name":"Yang"},{"first_name":"Prisca","last_name":"Liberali","full_name":"Liberali, Prisca"},{"last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","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).","year":"2025","oa_version":"Published Version","doi":"10.1038/s41567-025-02792-1","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","publication_status":"epub_ahead","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","publication":"Nature Physics","citation":{"ieee":"S. Xue, Q. Yang, P. Liberali, and E. B. Hannezo, “Mechanochemical bistability of intestinal organoids enables robust morphogenesis,” <i>Nature Physics</i>. Springer Nature, 2025.","short":"S. Xue, Q. Yang, P. Liberali, E.B. Hannezo, Nature Physics (2025).","chicago":"Xue, Shi-lei, Qiutan Yang, Prisca Liberali, and Edouard B Hannezo. “Mechanochemical Bistability of Intestinal Organoids Enables Robust Morphogenesis.” <i>Nature Physics</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41567-025-02792-1\">https://doi.org/10.1038/s41567-025-02792-1</a>.","mla":"Xue, Shi-lei, et al. “Mechanochemical Bistability of Intestinal Organoids Enables Robust Morphogenesis.” <i>Nature Physics</i>, 078104, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41567-025-02792-1\">10.1038/s41567-025-02792-1</a>.","ama":"Xue S, Yang Q, Liberali P, Hannezo EB. Mechanochemical bistability of intestinal organoids enables robust morphogenesis. <i>Nature Physics</i>. 2025. doi:<a href=\"https://doi.org/10.1038/s41567-025-02792-1\">10.1038/s41567-025-02792-1</a>","apa":"Xue, S., Yang, Q., Liberali, P., &#38; Hannezo, E. B. (2025). Mechanochemical bistability of intestinal organoids enables robust morphogenesis. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-025-02792-1\">https://doi.org/10.1038/s41567-025-02792-1</a>","ista":"Xue S, Yang Q, Liberali P, Hannezo EB. 2025. Mechanochemical bistability of intestinal organoids enables robust morphogenesis. Nature Physics., 078104."},"date_published":"2025-02-28T00:00:00Z"}