[{"publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"day":"01","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2025","license":"https://creativecommons.org/licenses/by/4.0/","corr_author":"1","file":[{"file_size":13514646,"content_type":"application/pdf","file_name":"2025_NatureImmunology_ReisRodrigues.pdf","creator":"dernst","file_id":"20096","checksum":"0c725123dca7797c682609bff2c4c5ac","success":1,"relation":"main_file","date_updated":"2025-07-31T08:00:33Z","date_created":"2025-07-31T08:00:33Z","access_level":"open_access"}],"OA_place":"publisher","abstract":[{"text":"Efficient immune responses rely on the capacity of leukocytes to traverse diverse and complex tissues. To meet such changing environmental conditions, leukocytes usually adopt an ameboid configuration, using their forward-positioned nucleus as a probe to identify and follow the path of least resistance among pre-existing pores. We show that, in dense environments where even the largest pores preclude free passage, leukocytes position their nucleus behind the centrosome and organelles. The local compression imposed on the cell body by its surroundings triggers assembly of a central F-actin pool, located between cell front and nucleus. Central actin pushes outward to transiently dilate a path for organelles and nucleus. Pools of central and front actin are tightly coupled and experimental depletion of the central pool enhances actin accumulation and protrusion formation at the cell front. Although this shifted balance speeds up cells in permissive environments, migration in restrictive environments is impaired, as the unleashed leading edge dissociates from the trapped cell body. Our findings establish an actin regulatory loop that balances path dilation with advancement of the leading edge to maintain cellular coherence.","lang":"eng"}],"publisher":"Springer Nature","page":"1258–1266","language":[{"iso":"eng"}],"acknowledgement":"This research was supported by the Scientific Service Units of ISTA through resources provided by the Imaging and Optics, Preclinical and Lab Support Facilities. In particular, we thank M. A. Symth and F. G. G. Leite, from the Virus Service Team, who helped generating the lentiviral particles used in this study. We thank all the members of the Sixt group for valuable discussions and feedback, in particular, I. Mayer, for helping with T cell isolation and Z. (P.) Li for providing the Actin–GFP DC line. We are also thankful to J. Mandl and C. Shen for their feedback during the writing of this manuscript. This work was supported by a European Research Council grant ERC-SyG 101071793 to M.S. M.J.A. was supported by an HFSP Postdoctoral Fellowship LTF 177 2021 and A.J.G. by a Lise Meitner Fellowship of the FWF (Austrian Science Fund). Y.F. was supported by the AMED-CREST (JP19gm1310005), the Medical Research Center Initiative for High Depth Omics and CURE:JPMXP1323015486 for MIB, Kyushu University. Open access funding provided by Institute of Science and Technology (IST Austria).","publication_status":"published","pmid":1,"citation":{"mla":"Dos Reis Rodrigues, Patricia, et al. “Migrating Immune Cells Globally Coordinate Protrusive Forces.” <i>Nature Immunology</i>, vol. 26, Springer Nature, 2025, pp. 1258–1266, doi:<a href=\"https://doi.org/10.1038/s41590-025-02211-w\">10.1038/s41590-025-02211-w</a>.","ama":"Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, et al. Migrating immune cells globally coordinate protrusive forces. <i>Nature Immunology</i>. 2025;26:1258–1266. doi:<a href=\"https://doi.org/10.1038/s41590-025-02211-w\">10.1038/s41590-025-02211-w</a>","short":"P. Dos Reis Rodrigues, M. Avellaneda Sarrió, N. Canigova, F.R. Gärtner, K. Vaahtomeri, M. Riedl, I. de Vries, J. Merrin, R. Hauschild, Y. Fukui, A. Juanes Garcia, M.K. Sixt, Nature Immunology 26 (2025) 1258–1266.","chicago":"Dos Reis Rodrigues, Patricia, Mario Avellaneda Sarrió, Nikola Canigova, Florian R Gärtner, Kari Vaahtomeri, Michael Riedl, Ingrid de Vries, et al. “Migrating Immune Cells Globally Coordinate Protrusive Forces.” <i>Nature Immunology</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41590-025-02211-w\">https://doi.org/10.1038/s41590-025-02211-w</a>.","ieee":"P. Dos Reis Rodrigues <i>et al.</i>, “Migrating immune cells globally coordinate protrusive forces,” <i>Nature Immunology</i>, vol. 26. Springer Nature, pp. 1258–1266, 2025.","ista":"Dos Reis Rodrigues P, Avellaneda Sarrió M, Canigova N, Gärtner FR, Vaahtomeri K, Riedl M, de Vries I, Merrin J, Hauschild R, Fukui Y, Juanes Garcia A, Sixt MK. 2025. Migrating immune cells globally coordinate protrusive forces. Nature Immunology. 26, 1258–1266.","apa":"Dos Reis Rodrigues, P., Avellaneda Sarrió, M., Canigova, N., Gärtner, F. R., Vaahtomeri, K., Riedl, M., … Sixt, M. K. (2025). Migrating immune cells globally coordinate protrusive forces. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-025-02211-w\">https://doi.org/10.1038/s41590-025-02211-w</a>"},"project":[{"grant_number":"101071793","name":"Pushing from within: Control of cell shape, integrity and motility by cytoskeletal pushing forces","_id":"bd91e723-d553-11ed-ba76-fe7eeb2185fd"},{"grant_number":"944-2020","name":"Bioelectric patrolling: the role of the local membrane potential in immune cell migration","_id":"c092d618-5a5b-11eb-8a69-f92e1e843fc8"}],"date_created":"2025-07-27T22:01:26Z","type":"journal_article","oa_version":"Published Version","oa":1,"intvolume":"        26","fulldoi":"https://doi.org/10.1038/s41590-025-02211-w","month":"08","publication":"Nature Immunology","status":"public","doi":"10.1038/s41590-025-02211-w","quality_controlled":"1","PlanS_conform":"1","date_published":"2025-08-01T00:00:00Z","article_type":"letter_note","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"OA_type":"hybrid","volume":26,"scopus_import":"1","_id":"20082","ddc":["570"],"author":[{"first_name":"Patricia","last_name":"Dos Reis Rodrigues","orcid":"0000-0003-1681-508X","full_name":"Dos Reis Rodrigues, Patricia","id":"26E95904-5160-11E9-9C0B-C5B0DC97E90F"},{"orcid":"0000-0001-6406-524X","full_name":"Avellaneda Sarrió, Mario","id":"DC4BA84C-56E6-11EA-AD5D-348C3DDC885E","first_name":"Mario","last_name":"Avellaneda Sarrió"},{"last_name":"Canigova","first_name":"Nikola","id":"3795523E-F248-11E8-B48F-1D18A9856A87","full_name":"Canigova, Nikola","orcid":"0000-0002-8518-5926"},{"first_name":"Florian R","last_name":"Gärtner","full_name":"Gärtner, Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Vaahtomeri","first_name":"Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","full_name":"Vaahtomeri, Kari","orcid":"0000-0001-7829-3518"},{"full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","first_name":"Michael","last_name":"Riedl"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid","last_name":"De Vries"},{"first_name":"Jack","last_name":"Merrin","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Robert","last_name":"Hauschild","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Fukui, Yoshinori","first_name":"Yoshinori","last_name":"Fukui"},{"id":"40F05888-F248-11E8-B48F-1D18A9856A87","full_name":"Juanes Garcia, Alba","orcid":"0000-0002-1009-9652","last_name":"Juanes Garcia","first_name":"Alba"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt"}],"isi":1,"has_accepted_license":"1","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"title":"Migrating immune cells globally coordinate protrusive forces","article_processing_charge":"Yes (via OA deal)","date_updated":"2026-04-28T13:26:50Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","related_material":{"record":[{"status":"public","id":"20149","relation":"dissertation_contains"}],"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/bench-pressing-cells/"}]},"external_id":{"pmid":["40664976"],"isi":["001529134300001"]},"file_date_updated":"2025-07-31T08:00:33Z"},{"author":[{"first_name":"Sergio","last_name":"Lembo","orcid":"0000-0002-2253-8771","full_name":"Lembo, Sergio","id":"d993a7b2-292f-11ed-aaac-fb045a912e31"},{"first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"scopus_import":"1","_id":"17191","volume":25,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","external_id":{"isi":["001251509300001"],"pmid":["38907047"]},"date_updated":"2025-09-08T08:06:56Z","title":"Nuclear squeezing wakes up dendritic cells","article_processing_charge":"No","doi":"10.1038/s41590-024-01881-2","status":"public","quality_controlled":"1","month":"06","publication":"Nature Immunology","date_published":"2024-06-21T00:00:00Z","article_type":"letter_note","department":[{"_id":"MiSi"}],"citation":{"mla":"Lembo, Sergio, and Michael K. Sixt. “Nuclear Squeezing Wakes up Dendritic Cells.” <i>Nature Immunology</i>, vol. 25, Springer Nature, 2024, pp. 1131–1132, doi:<a href=\"https://doi.org/10.1038/s41590-024-01881-2\">10.1038/s41590-024-01881-2</a>.","ama":"Lembo S, Sixt MK. Nuclear squeezing wakes up dendritic cells. <i>Nature Immunology</i>. 2024;25:1131–1132. doi:<a href=\"https://doi.org/10.1038/s41590-024-01881-2\">10.1038/s41590-024-01881-2</a>","short":"S. Lembo, M.K. Sixt, Nature Immunology 25 (2024) 1131–1132.","chicago":"Lembo, Sergio, and Michael K Sixt. “Nuclear Squeezing Wakes up Dendritic Cells.” <i>Nature Immunology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41590-024-01881-2\">https://doi.org/10.1038/s41590-024-01881-2</a>.","ieee":"S. Lembo and M. K. Sixt, “Nuclear squeezing wakes up dendritic cells,” <i>Nature Immunology</i>, vol. 25. Springer Nature, pp. 1131–1132, 2024.","apa":"Lembo, S., &#38; Sixt, M. K. (2024). Nuclear squeezing wakes up dendritic cells. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-024-01881-2\">https://doi.org/10.1038/s41590-024-01881-2</a>","ista":"Lembo S, Sixt MK. 2024. Nuclear squeezing wakes up dendritic cells. Nature Immunology. 25, 1131–1132."},"publication_status":"published","pmid":1,"oa_version":"None","type":"journal_article","fulldoi":"https://doi.org/10.1038/s41590-024-01881-2","intvolume":"        25","date_created":"2024-06-30T22:01:05Z","year":"2024","corr_author":"1","day":"21","publication_identifier":{"eissn":["1529-2916"],"issn":["1529-2908"]},"language":[{"iso":"eng"}],"page":"1131–1132 ","publisher":"Springer Nature","abstract":[{"lang":"eng","text":"Dendritic cells migrate to and from lymph nodes in response to chemokine gradients.Data now show that steady-state migration of these cells can be triggered by a mechanosensitive pathway."}]},{"publication":"Nature Immunology","month":"07","quality_controlled":"1","status":"public","doi":"10.1038/s41590-022-01257-4","ec_funded":1,"department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"date_published":"2022-07-11T00:00:00Z","article_type":"original","volume":23,"_id":"9794","scopus_import":"1","isi":1,"author":[{"last_name":"Assen","first_name":"Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P"},{"last_name":"Abe","first_name":"Jun","full_name":"Abe, Jun"},{"first_name":"Miroslav","last_name":"Hons","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","last_name":"Hauschild"},{"first_name":"Shayan","last_name":"Shamipour","full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"id":"D93824F4-D9BA-11E9-BB12-F207E6697425","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","last_name":"Costanzo","first_name":"Tommaso"},{"last_name":"Krens","first_name":"Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996"},{"first_name":"Markus","last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Ludewig, Burkhard","first_name":"Burkhard","last_name":"Ludewig"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"},{"first_name":"Wolfgang","last_name":"Weninger","full_name":"Weninger, Wolfgang"},{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","last_name":"Hannezo"},{"full_name":"Luther, Sanjiv A.","first_name":"Sanjiv A.","last_name":"Luther"},{"last_name":"Stein","first_name":"Jens V.","full_name":"Stein, Jens V."},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K"}],"ddc":["570"],"article_processing_charge":"No","title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","date_updated":"2025-06-11T13:52:43Z","has_accepted_license":"1","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"external_id":{"pmid":["35817845"],"isi":["000822975900002"]},"file_date_updated":"2022-07-25T07:11:32Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"file":[{"date_created":"2022-07-25T07:11:32Z","relation":"main_file","date_updated":"2022-07-25T07:11:32Z","access_level":"open_access","creator":"dernst","file_id":"11642","checksum":"628e7b49809f22c75b428842efe70c68","success":1,"file_size":11475325,"file_name":"2022_NatureImmunology_Assen.pdf","content_type":"application/pdf"}],"day":"11","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"year":"2022","corr_author":"1","abstract":[{"lang":"eng","text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion."}],"publisher":"Springer Nature","page":"1246-1255","language":[{"iso":"eng"}],"pmid":1,"publication_status":"published","citation":{"short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>.","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>.","ieee":"F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature, pp. 1246–1255, 2022.","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>","ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255."},"acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients","call_identifier":"H2020"}],"date_created":"2021-08-06T09:09:11Z","oa":1,"intvolume":"        23","fulldoi":"https://doi.org/10.1038/s41590-022-01257-4","type":"journal_article","oa_version":"Published Version"}]