Quantifying mechanical forces during vertebrate morphogenesis

Quantifying mechanical forces during vertebrate morphogenesis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Quantifying mechanical forces during vertebrate morphogenesis Eirini Maniou, Silvia Todros, Anna Urciuolo, Dale Moulding, Michael Magnusson, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1095730/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jul, 2024 Read the published version in Nature Materials → Version 1 posted You are reading this latest preprint version Abstract Morphogenesis, the establishment of rudimentary organ structures, requires embryonic cells to generate forces and perform mechanical work to shape their tissues. Incorrect functioning of these force fields can lead to congenital malformations including neural tube defects. The understanding of these dynamic processes requires quantification and profiling of three-dimensional mechanics during evolving vertebrate morphogenesis, which is not tractable with current technology. We fabricated elastic spring-like force sensors with micron-level resolution directly into specific three-dimensional domains of the closing neural tubes of growing chicken embryos through intravital three-dimensional bioprinting. Integration of calibrated sensor readouts with computational mechanical modelling allows direct quantification of forces and work performed by embryonic tissues. The two halves of the closing neural tube at the embryonic midline reach over a hundred nano-Newton compression during neural fold apposition. Unexpectedly, diminishing pro-closure force by pharmacologically inhibiting Rho-associated kinase reveals active anti-closure forces which must depend on alternative mechanisms or tissue properties, and which progressively widen the neural tube. Pro-morphogenetic forces must therefore overcome anti-morphogenetic forces to achieve neural tube closure. Force-sensor embryo biomechanics neural tube intravital bioprinting Full Text Additional Declarations Yes there is potential Competing Interest. Elvassore Nicola is a co-funder of Onyel Biotech. Supplementary Files Supplementarymaterialv13.pdf Cite Share Download PDF Status: Published Journal Publication published 05 Jul, 2024 Read the published version in Nature Materials → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1095730","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":84073036,"identity":"3df39f77-3501-4aa8-b7b3-8c69f90a8246","order_by":0,"name":"Eirini Maniou","email":"","orcid":"","institution":"Developmental Biology and Cancer, UCL GOS Institute of Child Health, London UK","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Eirini","middleName":"","lastName":"Maniou","suffix":""},{"id":84073037,"identity":"5b2a44eb-69ef-43ea-aeee-dcb689691697","order_by":1,"name":"Silvia Todros","email":"","orcid":"","institution":"Department of Industrial Engineering, University of Padova, Padova, Italy","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Silvia","middleName":"","lastName":"Todros","suffix":""},{"id":84073038,"identity":"45a75ffa-852c-4035-a9d8-4d00fbf72c8c","order_by":2,"name":"Anna Urciuolo","email":"","orcid":"https://orcid.org/0000-0001-7571-9747","institution":"Department of Industrial Engineering, University of Padova, Padova, Italy; Fondazione Istituto di Ricerca Pediatrica, Città della Speranza, Padova, Italy","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Urciuolo","suffix":""},{"id":84073039,"identity":"85938dfe-e0e5-46f7-adea-ae7061479ee2","order_by":3,"name":"Dale Moulding","email":"","orcid":"https://orcid.org/0000-0002-1431-7047","institution":"Developmental Biology and Cancer, UCL GOS Institute of Child Health, London UK","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dale","middleName":"","lastName":"Moulding","suffix":""},{"id":84073042,"identity":"c36a8f49-c909-4238-8f68-783011731ede","order_by":4,"name":"Michael Magnusson","email":"","orcid":"https://orcid.org/0000-0003-3054-9806","institution":"Developmental Biology and Cancer, UCL GOS Institute of Child Health, London UK","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Magnusson","suffix":""},{"id":84073040,"identity":"d081ca0f-284a-4229-929d-9ac23804c90b","order_by":5,"name":"Monica Giomo","email":"","orcid":"https://orcid.org/0000-0002-7690-1054","institution":"Department of Industrial Engineering, University of Padova, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Monica","middleName":"","lastName":"Giomo","suffix":""},{"id":84073041,"identity":"2f4b0b70-8b22-47aa-8e02-53ac8f4317ac","order_by":6,"name":"Piero G. 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Incorrect functioning of these force fields can lead to congenital malformations including neural tube defects. The understanding of these dynamic processes requires quantification and profiling of three-dimensional mechanics during evolving vertebrate morphogenesis, which is not tractable with current technology. We fabricated elastic spring-like force sensors with micron-level resolution directly into specific three-dimensional domains of the closing neural tubes of growing chicken embryos through intravital three-dimensional bioprinting. Integration of calibrated sensor readouts with computational mechanical modelling allows direct quantification of forces and work performed by embryonic tissues. The two halves of the closing neural tube at the embryonic midline reach over a hundred nano-Newton compression during neural fold apposition. 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Pro-morphogenetic forces must therefore overcome anti-morphogenetic forces to achieve neural tube closure.","manuscriptTitle":"Quantifying mechanical forces during vertebrate morphogenesis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-02-17 21:59:31","doi":"10.21203/rs.3.rs-1095730/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-materials","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"nmat","sideBox":"Learn more about [Nature Materials](http://www.nature.com/nmat/)","snPcode":"","submissionUrl":"","title":"Nature Materials","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c3d16c50-8297-4d2c-ad72-901283e2847a","owner":[],"postedDate":"February 17th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[{"value":"featured","date":"2022-02-18 20:25:35"}],"updatedAt":"2024-07-06T07:06:42+00:00","versionOfRecord":{"articleIdentity":"rs-1095730","link":"https://doi.org/10.1038/s41563-024-01942-9","journal":{"identity":"nature-materials","isVorOnly":false,"title":"Nature Materials"},"publishedOn":"2024-07-05 04:00:00","publishedOnDateReadable":"July 5th, 2024"},"versionCreatedAt":"2022-02-17 21:59:31","video":"","vorDoi":"10.1038/s41563-024-01942-9","vorDoiUrl":"https://doi.org/10.1038/s41563-024-01942-9","workflowStages":[]},"version":"v1","identity":"rs-1095730","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1095730","identity":"rs-1095730","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}