[{"pmid":1,"oa_version":"Published Version","abstract":[{"text":"Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events.","lang":"eng"}],"month":"12","intvolume":" 55","scopus_import":"1","file":[{"date_created":"2023-01-23T10:18:48Z","file_name":"2022_Immunity_Petzold.pdf","creator":"dernst","date_updated":"2023-01-23T10:18:48Z","file_size":5299475,"file_id":"12341","checksum":"073267a9c0ad9f85a650053bc7b23777","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1074-7613"]},"publication_status":"published","issue":"12","volume":55,"ec_funded":1,"_id":"12119","status":"public","keyword":["Infectious Diseases","Immunology","Immunology and Allergy"],"article_type":"original","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"ddc":["570"],"date_updated":"2023-08-03T14:21:51Z","department":[{"_id":"MiSi"}],"file_date_updated":"2023-01-23T10:18:48Z","acknowledgement":"We thank Coung Kieu and Dominik van den Heuvel for excellent technical assistance. This work was supported by the German Research Foundation (PE2704/2-1, PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR 332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12 to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G. was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’ by the German Federal\r\nMinistry of Education and Research to the German Center for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care through the research project DigiMed Bayern.","quality_controlled":"1","publisher":"Elsevier","oa":1,"day":"13","publication":"Immunity","has_accepted_license":"1","isi":1,"year":"2022","date_published":"2022-12-13T00:00:00Z","doi":"10.1016/j.immuni.2022.10.001","date_created":"2023-01-12T11:56:54Z","page":"2285-2299.e7","project":[{"grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin, Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity. Elsevier, 2022. https://doi.org/10.1016/j.immuni.2022.10.001.","ista":"Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 55(12), 2285–2299.e7.","mla":"Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity, vol. 55, no. 12, Elsevier, 2022, p. 2285–2299.e7, doi:10.1016/j.immuni.2022.10.001.","short":"T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L. Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S. Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach, E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian, F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity 55 (2022) 2285–2299.e7.","ieee":"T. Petzold et al., “Neutrophil ‘plucking’ on megakaryocytes drives platelet production and boosts cardiovascular disease,” Immunity, vol. 55, no. 12. Elsevier, p. 2285–2299.e7, 2022.","apa":"Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M., … Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2022.10.001","ama":"Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 2022;55(12):2285-2299.e7. doi:10.1016/j.immuni.2022.10.001"},"title":"Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease","author":[{"full_name":"Petzold, Tobias","last_name":"Petzold","first_name":"Tobias"},{"full_name":"Zhang, Zhe","last_name":"Zhang","first_name":"Zhe"},{"first_name":"Iván","last_name":"Ballesteros","full_name":"Ballesteros, Iván"},{"first_name":"Inas","full_name":"Saleh, Inas","last_name":"Saleh"},{"full_name":"Polzin, Amin","last_name":"Polzin","first_name":"Amin"},{"last_name":"Thienel","full_name":"Thienel, Manuela","first_name":"Manuela"},{"first_name":"Lulu","last_name":"Liu","full_name":"Liu, Lulu"},{"first_name":"Qurrat","last_name":"Ul Ain","full_name":"Ul Ain, Qurrat"},{"last_name":"Ehreiser","full_name":"Ehreiser, Vincent","first_name":"Vincent"},{"full_name":"Weber, Christian","last_name":"Weber","first_name":"Christian"},{"last_name":"Kilani","full_name":"Kilani, Badr","first_name":"Badr"},{"first_name":"Pontus","last_name":"Mertsch","full_name":"Mertsch, Pontus"},{"full_name":"Götschke, Jeremias","last_name":"Götschke","first_name":"Jeremias"},{"full_name":"Cremer, Sophie","last_name":"Cremer","first_name":"Sophie"},{"full_name":"Fu, Wenwen","last_name":"Fu","first_name":"Wenwen"},{"last_name":"Lorenz","full_name":"Lorenz, Michael","first_name":"Michael"},{"full_name":"Ishikawa-Ankerhold, Hellen","last_name":"Ishikawa-Ankerhold","first_name":"Hellen"},{"first_name":"Elisabeth","full_name":"Raatz, Elisabeth","last_name":"Raatz"},{"last_name":"El-Nemr","full_name":"El-Nemr, Shaza","first_name":"Shaza"},{"last_name":"Görlach","full_name":"Görlach, Agnes","first_name":"Agnes"},{"full_name":"Marhuenda, Esther","last_name":"Marhuenda","first_name":"Esther"},{"last_name":"Stark","full_name":"Stark, Konstantin","first_name":"Konstantin"},{"full_name":"Pircher, Joachim","last_name":"Pircher","first_name":"Joachim"},{"last_name":"Stegner","full_name":"Stegner, David","first_name":"David"},{"first_name":"Christian","full_name":"Gieger, Christian","last_name":"Gieger"},{"first_name":"Marc","last_name":"Schmidt-Supprian","full_name":"Schmidt-Supprian, Marc"},{"first_name":"Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","last_name":"Gärtner","orcid":"0000-0001-6120-3723","full_name":"Gärtner, Florian R"},{"first_name":"Isaac","last_name":"Almendros","full_name":"Almendros, Isaac"},{"first_name":"Malte","full_name":"Kelm, Malte","last_name":"Kelm"},{"first_name":"Christian","last_name":"Schulz","full_name":"Schulz, Christian"},{"first_name":"Andrés","full_name":"Hidalgo, Andrés","last_name":"Hidalgo"},{"last_name":"Massberg","full_name":"Massberg, Steffen","first_name":"Steffen"}],"external_id":{"pmid":["36272416"],"isi":["000922019600003"]},"article_processing_charge":"No"},{"issue":"12","volume":22,"publication_identifier":{"issn":["1474-1733"],"eissn":["1474-1741"]},"publication_status":"published","language":[{"iso":"eng"}],"scopus_import":"1","month":"12","intvolume":" 22","abstract":[{"lang":"eng","text":"Social distancing is an effective way to prevent the spread of disease in societies, whereas infection elimination is a key element of organismal immunity. Here, we discuss how the study of social insects such as ants — which form a superorganism of unconditionally cooperative individuals and thus represent a level of organization that is intermediate between a classical society of individuals and an organism of cells — can help to determine common principles of disease defence across levels of organization."}],"oa_version":"None","pmid":1,"department":[{"_id":"SyCr"},{"_id":"MiSi"}],"date_updated":"2023-08-04T08:53:32Z","article_type":"letter_note","type":"journal_article","status":"public","keyword":["Energy Engineering and Power Technology","Fuel Technology"],"_id":"12133","page":"713-714","doi":"10.1038/s41577-022-00797-y","date_published":"2022-12-01T00:00:00Z","date_created":"2023-01-12T12:03:14Z","isi":1,"year":"2022","day":"01","publication":"Nature Reviews Immunology","publisher":"Springer Nature","quality_controlled":"1","author":[{"first_name":"Sylvia","id":"2F64EC8C-F248-11E8-B48F-1D18A9856A87","full_name":"Cremer, Sylvia","orcid":"0000-0002-2193-3868","last_name":"Cremer"},{"orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"external_id":{"isi":["000871836300001"],"pmid":["36284178"]},"article_processing_charge":"No","title":"Principles of disease defence in organisms, superorganisms and societies","citation":{"ista":"Cremer S, Sixt MK. 2022. Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. 22(12), 713–714.","chicago":"Cremer, Sylvia, and Michael K Sixt. “Principles of Disease Defence in Organisms, Superorganisms and Societies.” Nature Reviews Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41577-022-00797-y.","short":"S. Cremer, M.K. Sixt, Nature Reviews Immunology 22 (2022) 713–714.","ieee":"S. Cremer and M. K. Sixt, “Principles of disease defence in organisms, superorganisms and societies,” Nature Reviews Immunology, vol. 22, no. 12. Springer Nature, pp. 713–714, 2022.","apa":"Cremer, S., & Sixt, M. K. (2022). Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. Springer Nature. https://doi.org/10.1038/s41577-022-00797-y","ama":"Cremer S, Sixt MK. Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. 2022;22(12):713-714. doi:10.1038/s41577-022-00797-y","mla":"Cremer, Sylvia, and Michael K. Sixt. “Principles of Disease Defence in Organisms, Superorganisms and Societies.” Nature Reviews Immunology, vol. 22, no. 12, Springer Nature, 2022, pp. 713–14, doi:10.1038/s41577-022-00797-y."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"title":"Plan your trip before you leave: The neutrophils’ search-and-run journey","external_id":{"pmid":["35856919"],"isi":["000874717200001"]},"article_processing_charge":"No","author":[{"first_name":"Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","full_name":"Stopp, Julian A","last_name":"Stopp"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"short":"J.A. Stopp, M.K. Sixt, Journal of Cell Biology 221 (2022).","ieee":"J. A. Stopp and M. K. Sixt, “Plan your trip before you leave: The neutrophils’ search-and-run journey,” Journal of Cell Biology, vol. 221, no. 8. Rockefeller University Press, 2022.","ama":"Stopp JA, Sixt MK. Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. 2022;221(8). doi:10.1083/jcb.202206127","apa":"Stopp, J. A., & Sixt, M. K. (2022). Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202206127","mla":"Stopp, Julian A., and Michael K. Sixt. “Plan Your Trip before You Leave: The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology, vol. 221, no. 8, e202206127, Rockefeller University Press, 2022, doi:10.1083/jcb.202206127.","ista":"Stopp JA, Sixt MK. 2022. Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. 221(8), e202206127.","chicago":"Stopp, Julian A, and Michael K Sixt. “Plan Your Trip before You Leave: The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology. Rockefeller University Press, 2022. https://doi.org/10.1083/jcb.202206127."},"article_number":"e202206127","date_created":"2023-01-16T10:01:08Z","date_published":"2022-07-20T00:00:00Z","doi":"10.1083/jcb.202206127","publication":"Journal of Cell Biology","day":"20","year":"2022","isi":1,"has_accepted_license":"1","oa":1,"publisher":"Rockefeller University Press","quality_controlled":"1","department":[{"_id":"MiSi"}],"file_date_updated":"2023-01-30T10:39:34Z","ddc":["570"],"date_updated":"2023-12-21T14:30:01Z","keyword":["Cell Biology"],"status":"public","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"article_type":"original","type":"journal_article","_id":"12272","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","related_material":{"record":[{"status":"public","id":"14697","relation":"dissertation_contains"}]},"volume":221,"issue":"8","language":[{"iso":"eng"}],"file":[{"file_name":"2022_JourCellBiology_Stopp.pdf","date_created":"2023-01-30T10:39:34Z","file_size":969969,"date_updated":"2023-01-30T10:39:34Z","creator":"dernst","success":1,"checksum":"6b1620743669679b48b9389bb40f5a11","file_id":"12451","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"publication_status":"published","publication_identifier":{"eissn":["1540-8140"],"issn":["0021-9525"]},"intvolume":" 221","month":"07","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"text":"Reading, interpreting and crawling along gradients of chemotactic cues is one of the most complex questions in cell biology. In this issue, Georgantzoglou et al. (2022. J. Cell. Biol.https://doi.org/10.1083/jcb.202103207) use in vivo models to map the temporal sequence of how neutrophils respond to an acutely arising gradient of chemoattractant.","lang":"eng"}]},{"project":[{"grant_number":"747687","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ieee":"F. Gaertner et al., “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” Developmental Cell, vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022.","short":"F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9.","apa":"Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. Cell Press ; Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024","ama":"Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024","mla":"Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell, vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024.","ista":"Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9.","chicago":"Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024."},"title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","author":[{"full_name":"Gaertner, Florian","last_name":"Gaertner","first_name":"Florian"},{"first_name":"Patricia","full_name":"Reis-Rodrigues, Patricia","last_name":"Reis-Rodrigues"},{"last_name":"De Vries","full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid"},{"id":"4167FE56-F248-11E8-B48F-1D18A9856A87","first_name":"Miroslav","full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","last_name":"Hons"},{"first_name":"Juan","full_name":"Aguilera, Juan","last_name":"Aguilera"},{"last_name":"Riedl","orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Leithner","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X","last_name":"Tasciyan"},{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","first_name":"Aglaja","last_name":"Kopf","orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja"},{"last_name":"Merrin","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack"},{"orcid":"0000-0002-9438-4783","full_name":"Zheden, Vanessa","last_name":"Zheden","first_name":"Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","last_name":"Hauschild"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"external_id":{"pmid":["34919802"],"isi":["000768933800005"]},"article_processing_charge":"No","acknowledgement":"We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687.","quality_controlled":"1","publisher":"Cell Press ; Elsevier","oa":1,"day":"10","publication":"Developmental Cell","isi":1,"year":"2022","date_published":"2022-01-10T00:00:00Z","doi":"10.1016/j.devcel.2021.11.024","date_created":"2022-01-30T23:01:33Z","page":"47-62.e9","_id":"10703","status":"public","article_type":"original","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"ddc":["570"],"date_updated":"2024-03-27T23:30:23Z","department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}],"oa_version":"Published Version","pmid":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"abstract":[{"text":"When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.","lang":"eng"}],"month":"01","intvolume":" 57","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"publication_status":"published","related_material":{"record":[{"relation":"dissertation_contains","id":"12726","status":"public"},{"id":"14530","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"12401"}]},"issue":"1","volume":57,"ec_funded":1},{"related_material":{"record":[{"status":"public","id":"679","relation":"part_of_dissertation"},{"id":"10703","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"9429"},{"relation":"part_of_dissertation","status":"public","id":"7885"}]},"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","file":[{"file_name":"PhD-Thesis_Saren Tasciyan_formatted_aftercrash_fixed_600dpi_95pc_final_PDFA3b.pdf","date_created":"2023-01-26T11:58:14Z","creator":"cchlebak","file_size":42059787,"date_updated":"2023-12-21T23:30:03Z","embargo":"2023-12-20","checksum":"cc4a2b4a7e3c4ee8ef7f2dbf909b12bd","file_id":"12402","relation":"main_file","access_level":"open_access","content_type":"application/pdf"},{"relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/x-zip-compressed","file_id":"12403","checksum":"f1b4ca98b8ab0cb043b1830971e9bd9c","creator":"cchlebak","file_size":261256696,"date_updated":"2023-12-21T23:30:03Z","file_name":"Source Files - Saren Tasciyan - PhD Thesis.zip","date_created":"2023-01-26T12:00:10Z"}],"language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"month":"12","abstract":[{"text":"Detachment of the cancer cells from the bulk of the tumor is the first step of metastasis, which\r\nis the primary cause of cancer related deaths. It is unclear, which factors contribute to this step.\r\nRecent studies indicate a crucial role of the tumor microenvironment in malignant\r\ntransformation and metastasis. Studying cancer cell invasion and detachments quantitatively in\r\nthe context of its physiological microenvironment is technically challenging. Especially, precise\r\ncontrol of microenvironmental properties in vivo is currently not possible. Here, I studied the\r\nrole of microenvironment geometry in the invasion and detachment of cancer cells from the\r\nbulk with a simplistic and reductionist approach. In this approach, I engineered microfluidic\r\ndevices to mimic a pseudo 3D extracellular matrix environment, where I was able to\r\nquantitatively tune the geometrical configuration of the microenvironment and follow tumor\r\ncells with fluorescence live imaging. To aid quantitative analysis I developed a widely applicable\r\nsoftware application to automatically analyze and visualize particle tracking data.\r\nQuantitative analysis of tumor cell invasion in isotropic and anisotropic microenvironments\r\nshowed that heterogeneity in the microenvironment promotes faster invasion and more\r\nfrequent detachment of cells. These observations correlated with overall higher speed of cells at\r\nthe edge of the bulk of the cells. In heterogeneous microenvironments cells preferentially\r\npassed through larger pores, thus invading areas of least resistance and generating finger-like\r\ninvasive structures. The detachments occurred mostly at the tips of these structures.\r\nTo investigate the potential mechanism, we established a two dimensional model to simulate\r\nactive Brownian particles representing the cell nuclei dynamics. These simulations backed our in\r\nvitro observations without the need of precise fitting the simulation parameters. Our model\r\nsuggests the importance of the pore heterogeneity in the direction perpendicular to the\r\norientation of bias field (lateral heterogeneity), which causes the interface roughening.","lang":"eng"}],"oa_version":"Published Version","file_date_updated":"2023-12-21T23:30:03Z","department":[{"_id":"GradSch"},{"_id":"MiSi"}],"supervisor":[{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-12-21T23:30:04Z","ddc":["610"],"type":"dissertation","status":"public","_id":"12401","page":"105","date_published":"2022-12-22T00:00:00Z","doi":"10.15479/at:ista:12401","date_created":"2023-01-26T11:55:16Z","has_accepted_license":"1","year":"2022","day":"22","publisher":"Institute of Science and Technology Austria","oa":1,"author":[{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","last_name":"Tasciyan","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X"}],"article_processing_charge":"No","title":"Role of microenvironment heterogeneity in cancer cell invasion","citation":{"mla":"Tasciyan, Saren. Role of Microenvironment Heterogeneity in Cancer Cell Invasion. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12401.","ieee":"S. Tasciyan, “Role of microenvironment heterogeneity in cancer cell invasion,” Institute of Science and Technology Austria, 2022.","short":"S. Tasciyan, Role of Microenvironment Heterogeneity in Cancer Cell Invasion, Institute of Science and Technology Austria, 2022.","ama":"Tasciyan S. Role of microenvironment heterogeneity in cancer cell invasion. 2022. doi:10.15479/at:ista:12401","apa":"Tasciyan, S. (2022). Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12401","chicago":"Tasciyan, Saren. “Role of Microenvironment Heterogeneity in Cancer Cell Invasion.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12401.","ista":"Tasciyan S. 2022. Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9"}]