[{"citation":{"chicago":"Boocock, Daniel R. “Mechanochemical Pattern Formation across Biological Scales.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12964.","mla":"Boocock, Daniel R. Mechanochemical Pattern Formation across Biological Scales. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12964.","short":"D.R. Boocock, Mechanochemical Pattern Formation across Biological Scales, Institute of Science and Technology Austria, 2023.","ista":"Boocock DR. 2023. Mechanochemical pattern formation across biological scales. Institute of Science and Technology Austria.","apa":"Boocock, D. R. (2023). Mechanochemical pattern formation across biological scales. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12964","ieee":"D. R. Boocock, “Mechanochemical pattern formation across biological scales,” Institute of Science and Technology Austria, 2023.","ama":"Boocock DR. Mechanochemical pattern formation across biological scales. 2023. doi:10.15479/at:ista:12964"},"page":"146","date_published":"2023-05-17T00:00:00Z","has_accepted_license":"1","article_processing_charge":"No","day":"17","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","_id":"12964","ddc":["530"],"status":"public","title":"Mechanochemical pattern formation across biological scales","file":[{"access_level":"closed","file_name":"thesis_boocock.pdf","embargo_to":"open_access","creator":"dboocock","content_type":"application/pdf","file_size":40414730,"file_id":"12988","embargo":"2024-05-17","relation":"main_file","checksum":"d51240675fc6dc0e3f5dc0c902695d3a","date_created":"2023-05-17T13:39:54Z","date_updated":"2023-05-19T07:04:25Z"},{"creator":"dboocock","file_size":34338567,"content_type":"application/zip","file_name":"thesis_boocock.zip","access_level":"closed","date_updated":"2023-05-17T14:35:13Z","date_created":"2023-05-17T13:39:53Z","checksum":"581a2313ffeb40fe77e8a122a25a7795","file_id":"12989","relation":"source_file"}],"oa_version":"Published Version","type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"text":"Pattern formation is of great importance for its contribution across different biological behaviours. During developmental processes for example, patterns of chemical gradients are\r\nestablished to determine cell fate and complex tissue patterns emerge to define structures such\r\nas limbs and vascular networks. Patterns are also seen in collectively migrating groups, for\r\ninstance traveling waves of density emerging in moving animal flocks as well as collectively migrating cells and tissues. To what extent these biological patterns arise spontaneously through\r\nthe local interaction of individual constituents or are dictated by higher level instructions is\r\nstill an open question however there is evidence for the involvement of both types of process.\r\nWhere patterns arise spontaneously there is a long standing interest in how far the interplay\r\nof mechanics, e.g. force generation and deformation, and chemistry, e.g. gene regulation\r\nand signaling, contributes to the behaviour. This is because many systems are able to both\r\nchemically regulate mechanical force production and chemically sense mechanical deformation,\r\nforming mechano-chemical feedback loops which can potentially become unstable towards\r\nspatio and/or temporal patterning.\r\nWe work with experimental collaborators to investigate the possibility that this type of\r\ninteraction drives pattern formation in biological systems at different scales. We focus first on\r\ntissue-level ERK-density waves observed during the wound healing response across different\r\nsystems where many previous studies have proposed that patterns depend on polarized cell\r\nmigration and arise from a mechanical flocking-like mechanism. By combining theory with\r\nmechanical and optogenetic perturbation experiments on in vitro monolayers we instead find\r\nevidence for mechanochemical pattern formation involving only scalar bilateral feedbacks\r\nbetween ERK signaling and cell contraction. We perform further modeling and experiment\r\nto study how this instability couples with polar cell migration in order to produce a robust\r\nand efficient wound healing response. In a following chapter we implement ERK-density\r\ncoupling and cell migration in a 2D active vertex model to investigate the interaction of\r\nERK-density patterning with different tissue rheologies and find that the spatio-temporal\r\ndynamics are able to both locally and globally fluidize a tissue across the solid-fluid glass\r\ntransition. In a last chapter we move towards lower spatial scales in the context of subcellular\r\npatterning of the cell cytoskeleton where we investigate the transition between phases of\r\nspatially homogeneous temporal oscillations and chaotic spatio-temporal patterning in the\r\ndynamics of myosin and ROCK activities (a motor component of the actomyosin cytoskeleton\r\nand its activator). Experimental evidence supports an intrinsic chemical oscillator which we\r\nencode in a reaction model and couple to a contractile active gel description of the cell cortex.\r\nThe model exhibits phases of chemical oscillations and contractile spatial patterning which\r\nreproduce many features of the dynamics seen in Drosophila oocyte epithelia in vivo. However,\r\nadditional pharmacological perturbations to inhibit myosin contractility leaves the role of\r\ncontractile instability unclear. We discuss alternative hypotheses and investigate the possibility\r\nof reaction-diffusion instability.","lang":"eng"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"project":[{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"doi":"10.15479/at:ista:12964","language":[{"iso":"eng"}],"supervisor":[{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","first_name":"Edouard B"}],"degree_awarded":"PhD","publication_identifier":{"isbn":["978-3-99078-032-9"],"issn":["2663-337X"]},"month":"05","year":"2023","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"EdHa"}],"publication_status":"published","related_material":{"record":[{"id":"8602","relation":"part_of_dissertation","status":"public"}]},"author":[{"id":"453AF628-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1585-2631","first_name":"Daniel R","last_name":"Boocock","full_name":"Boocock, Daniel R"}],"date_created":"2023-05-15T14:52:36Z","date_updated":"2023-08-04T11:02:40Z","ec_funded":1,"file_date_updated":"2023-05-19T07:04:25Z","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/"},{"oa_version":"Published Version","file":[{"creator":"dernst","content_type":"application/pdf","file_size":2559520,"access_level":"open_access","file_name":"2023_PRXLife_Boocock.pdf","success":1,"checksum":"f881d98c89eb9f1aa136d7b781511553","date_created":"2023-09-15T06:30:50Z","date_updated":"2023-09-15T06:30:50Z","file_id":"14335","relation":"main_file"}],"intvolume":" 1","ddc":["570"],"status":"public","title":"Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14277","issue":"1","abstract":[{"lang":"eng","text":"Living tissues are characterized by an intrinsically mechanochemical interplay of active physical forces and complex biochemical signaling pathways. Either feature alone can give rise to complex emergent phenomena, for example, mechanically driven glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion instabilities. An important question is how to quantitatively assess the contribution of these different cues to the large-scale dynamics of biological materials. We address this in Madin-Darby canine kidney (MDCK) monolayers, considering both mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling activity and cellular density as well as a mechanically active tissue rheology via a self-propelled vertex model. We show that the relative strength of active migration forces to mechanochemical couplings controls a transition from a uniform active glass to periodic spatiotemporal waves. We parametrize the model from published experimental data sets on MDCK monolayers and use it to make new predictions on the correlation functions of cellular dynamics and the dynamics of topological defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers are best described by an intermediary parameter region in which both mechanochemical couplings and noisy active propulsion have a strong influence on the dynamics. Finally, we study how tissue rheology and ERK waves produce feedback on one another and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical waves at both the local and global levels."}],"type":"journal_article","date_published":"2023-07-20T00:00:00Z","article_type":"original","citation":{"ama":"Boocock DR, Hirashima T, Hannezo EB. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 2023;1(1). doi:10.1103/prxlife.1.013001","ieee":"D. R. Boocock, T. Hirashima, and E. B. Hannezo, “Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers,” PRX Life, vol. 1, no. 1. American Physical Society, 2023.","apa":"Boocock, D. R., Hirashima, T., & Hannezo, E. B. (2023). Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. American Physical Society. https://doi.org/10.1103/prxlife.1.013001","ista":"Boocock DR, Hirashima T, Hannezo EB. 2023. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 1(1), 013001.","short":"D.R. Boocock, T. Hirashima, E.B. Hannezo, PRX Life 1 (2023).","mla":"Boocock, Daniel R., et al. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” PRX Life, vol. 1, no. 1, 013001, American Physical Society, 2023, doi:10.1103/prxlife.1.013001.","chicago":"Boocock, Daniel R, Tsuyoshi Hirashima, and Edouard B Hannezo. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” PRX Life. American Physical Society, 2023. https://doi.org/10.1103/prxlife.1.013001."},"publication":"PRX Life","has_accepted_license":"1","article_processing_charge":"Yes","day":"20","volume":1,"date_created":"2023-09-06T08:30:59Z","date_updated":"2023-09-15T06:39:17Z","author":[{"id":"453AF628-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1585-2631","first_name":"Daniel R","last_name":"Boocock","full_name":"Boocock, Daniel R"},{"first_name":"Tsuyoshi","last_name":"Hirashima","full_name":"Hirashima, Tsuyoshi"},{"full_name":"Hannezo, Edouard B","last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"EdHa"}],"publisher":"American Physical Society","publication_status":"published","acknowledgement":"We thank all members of the Hannezo group for discussions and suggestions, as well as Sound Wai Phow for technical assistance. This work received funding from the European Research Council under the EU Horizon 2020 research and innovation program Grant Agreement No. 851288 (E.H.), JSPS KAKENHI Grant No. 21H05290, and the Ministry of Education under the Research Centres of Excellence program through the MBI at NUS.","year":"2023","license":"https://creativecommons.org/licenses/by/4.0/","ec_funded":1,"file_date_updated":"2023-09-15T06:30:50Z","article_number":"013001","language":[{"iso":"eng"}],"doi":"10.1103/prxlife.1.013001","project":[{"name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288"}],"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"publication_identifier":{"issn":["2835-8279"]},"month":"07"},{"type":"journal_article","abstract":[{"text":"Collective cell migration offers a rich field of study for non-equilibrium physics and cellular biology, revealing phenomena such as glassy dynamics, pattern formation and active turbulence. However, how mechanical and chemical signalling are integrated at the cellular level to give rise to such collective behaviours remains unclear. We address this by focusing on the highly conserved phenomenon of spatiotemporal waves of density and extracellular signal-regulated kinase (ERK) activation, which appear both in vitro and in vivo during collective cell migration and wound healing. First, we propose a biophysical theory, backed by mechanical and optogenetic perturbation experiments, showing that patterns can be quantitatively explained by a mechanochemical coupling between active cellular tensions and the mechanosensitive ERK pathway. Next, we demonstrate how this biophysical mechanism can robustly induce long-ranged order and migration in a desired orientation, and we determine the theoretically optimal wavelength and period for inducing maximal migration towards free edges, which fits well with experimentally observed dynamics. We thereby provide a bridge between the biophysical origin of spatiotemporal instabilities and the design principles of robust and efficient long-ranged migration.","lang":"eng"}],"intvolume":" 17","status":"public","title":"Theory of mechanochemical patterning and optimal migration in cell monolayers","_id":"8602","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Preprint","scopus_import":"1","article_processing_charge":"No","day":"01","page":"267-274","article_type":"original","citation":{"chicago":"Boocock, Daniel R, Naoya Hino, Natalia Ruzickova, Tsuyoshi Hirashima, and Edouard B Hannezo. “Theory of Mechanochemical Patterning and Optimal Migration in Cell Monolayers.” Nature Physics. Springer Nature, 2021. https://doi.org/10.1038/s41567-020-01037-7.","mla":"Boocock, Daniel R., et al. “Theory of Mechanochemical Patterning and Optimal Migration in Cell Monolayers.” Nature Physics, vol. 17, Springer Nature, 2021, pp. 267–74, doi:10.1038/s41567-020-01037-7.","short":"D.R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, E.B. Hannezo, Nature Physics 17 (2021) 267–274.","ista":"Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. 2021. Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. 17, 267–274.","ieee":"D. R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, and E. B. Hannezo, “Theory of mechanochemical patterning and optimal migration in cell monolayers,” Nature Physics, vol. 17. Springer Nature, pp. 267–274, 2021.","apa":"Boocock, D. R., Hino, N., Ruzickova, N., Hirashima, T., & Hannezo, E. B. (2021). Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-020-01037-7","ama":"Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. 2021;17:267-274. doi:10.1038/s41567-020-01037-7"},"publication":"Nature Physics","date_published":"2021-02-01T00:00:00Z","ec_funded":1,"publisher":"Springer Nature","department":[{"_id":"EdHa"}],"publication_status":"published","year":"2021","acknowledgement":"We would like to thank G. Tkacik and all of the members of the Hannezo and Hirashima groups for useful discussions, X. Trepat for help on traction force microscopy and M. Matsuda for use of the lab facility. E.H. acknowledges grants from the Austrian Science Fund (FWF) (P 31639) and the European Research Council (851288). T.H. acknowledges a grant from JST, PRESTO (JPMJPR1949). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 665385 (to D.B.), from JSPS KAKENHI grant no. 17J02107 (to N.H.) and from the SPIRITS 2018 of Kyoto University (to E.H. and T.H.).","volume":17,"date_created":"2020-10-04T22:01:37Z","date_updated":"2023-08-04T11:02:41Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12964"}],"link":[{"url":"https://ist.ac.at/en/news/wound-healing-waves/","relation":"press_release","description":"News on IST Homepage"}]},"author":[{"full_name":"Boocock, Daniel R","orcid":"0000-0002-1585-2631","id":"453AF628-F248-11E8-B48F-1D18A9856A87","last_name":"Boocock","first_name":"Daniel R"},{"first_name":"Naoya","last_name":"Hino","full_name":"Hino, Naoya"},{"first_name":"Natalia","last_name":"Ruzickova","id":"D2761128-D73D-11E9-A1BF-BA0DE6697425","full_name":"Ruzickova, Natalia"},{"full_name":"Hirashima, Tsuyoshi","first_name":"Tsuyoshi","last_name":"Hirashima"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B"}],"publication_identifier":{"eissn":["17452481"],"issn":["17452473"]},"month":"02","project":[{"grant_number":"P31639","_id":"268294B6-B435-11E9-9278-68D0E5697425","name":"Active mechano-chemical description of the cell cytoskeleton","call_identifier":"FWF"},{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"}],"quality_controlled":"1","isi":1,"main_file_link":[{"url":"https://doi.org/10.1101/2020.05.15.096479","open_access":"1"}],"external_id":{"isi":["000573519500002"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1038/s41567-020-01037-7"}]