[{"status":"public","scopus_import":"1","ec_funded":1,"file_date_updated":"2022-08-16T08:57:37Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"isi":1,"date_updated":"2025-04-15T07:17:32Z","publication":"eLife","year":"2022","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"        11","article_number":"e78995","date_published":"2022-07-26T00:00:00Z","type":"journal_article","quality_controlled":"1","abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"_id":"11843","language":[{"iso":"eng"}],"external_id":{"pmid":["35881547"],"isi":["000838410200001"]},"has_accepted_license":"1","day":"26","citation":{"chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>."},"publisher":"eLife Sciences Publications","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","article_processing_charge":"Yes","pmid":1,"related_material":{"record":[{"relation":"earlier_version","status":"public","id":"10316"}]},"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","doi":"10.7554/eLife.78995","oa":1,"article_type":"original","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients"},{"grant_number":"P29911","call_identifier":"FWF","_id":"26018E70-B435-11E9-9278-68D0E5697425","name":"Mechanical adaptation of lamellipodial actin"}],"department":[{"_id":"MiSi"},{"_id":"CaGu"}],"month":"07","volume":11,"author":[{"orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin","last_name":"Tomasek","full_name":"Tomasek, Kathrin"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F"},{"full_name":"Glatzová, Ivana","last_name":"Glatzová","first_name":"Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"first_name":"Michael S.","full_name":"Lukesch, Michael S.","last_name":"Lukesch"},{"last_name":"Guet","full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"publication_identifier":{"eissn":["2050-084X"]},"oa_version":"Published Version","date_created":"2022-08-14T22:01:46Z","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","publication_status":"published","file":[{"success":1,"content_type":"application/pdf","file_size":2057577,"date_created":"2022-08-16T08:57:37Z","access_level":"open_access","relation":"main_file","date_updated":"2022-08-16T08:57:37Z","creator":"cchlebak","file_id":"11861","checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","file_name":"2022_eLife_Tomasek.pdf"}]},{"oa_version":"Preprint","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1"}],"date_published":"2021-10-18T00:00:00Z","date_created":"2021-11-19T12:24:16Z","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","year":"2021","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, <a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>."},"day":"18","type":"preprint","publication_status":"draft","_id":"10316","abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"id":"11843","status":"public","relation":"later_version"},{"relation":"dissertation_contains","id":"10307","status":"public"}]},"ec_funded":1,"publisher":"Cold Spring Harbor Laboratory","status":"public","corr_author":"1","article_processing_charge":"No","project":[{"name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373"},{"name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911","call_identifier":"FWF","_id":"26018E70-B435-11E9-9278-68D0E5697425"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"month":"10","department":[{"_id":"CaGu"},{"_id":"MiSi"}],"publication":"bioRxiv","date_updated":"2026-04-27T22:30:39Z","author":[{"full_name":"Tomasek, Kathrin","last_name":"Tomasek","first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X"},{"first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","last_name":"Leithner","full_name":"Leithner, Alexander F"},{"full_name":"Glatzová, Ivana","last_name":"Glatzová","first_name":"Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"first_name":"Michael S.","full_name":"Lukesch, Michael S.","last_name":"Lukesch"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C","last_name":"Guet"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","last_name":"Sixt"}],"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","oa":1,"doi":"10.1101/2021.10.18.464770"},{"month":"06","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"project":[{"name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556","call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425"},{"name":"Cellular Navigation Along Spatial Gradients","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"},{"name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911","call_identifier":"FWF","_id":"26018E70-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"252C3B08-B435-11E9-9278-68D0E5697425","grant_number":"W1250-B20","name":"Nano-Analytics of Cellular Systems"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"name":"Molecular and system level view of immune cell migration","_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014"}],"article_type":"original","volume":219,"author":[{"full_name":"Kopf, Aglaja","last_name":"Kopf","first_name":"Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656"},{"last_name":"Renkawitz","full_name":"Renkawitz, Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","first_name":"Jörg"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert"},{"first_name":"Irute","last_name":"Girkontaite","full_name":"Girkontaite, Irute"},{"full_name":"Tedford, Kerry","last_name":"Tedford","first_name":"Kerry"},{"last_name":"Merrin","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Thorn-Seshold, Oliver","last_name":"Thorn-Seshold","first_name":"Oliver"},{"first_name":"Dirk","id":"E8F27F48-3EBA-11E9-92A1-B709E6697425","last_name":"Trauner","full_name":"Trauner, Dirk"},{"last_name":"Häcker","full_name":"Häcker, Hans","first_name":"Hans"},{"last_name":"Fischer","full_name":"Fischer, Klaus Dieter","first_name":"Klaus Dieter"},{"full_name":"Kiermaier, Eva","last_name":"Kiermaier","first_name":"Eva","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6165-5738"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","full_name":"Sixt, Michael K"}],"oa":1,"doi":"10.1083/jcb.201907154","acknowledgement":"The authors thank the Scientific Service Units (Life Sciences, Bioimaging, Preclinical) of the Institute of Science and Technology Austria for excellent support. This work was funded by the European Research Council (ERC StG 281556 and CoG 724373), two grants from the Austrian\r\nScience Fund (FWF; P29911 and DK Nanocell W1250-B20 to M. Sixt) and by the German Research Foundation (DFG SFB1032 project B09) to O. Thorn-Seshold and D. Trauner. J. Renkawitz was supported by ISTFELLOW funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under the Research Executive Agency grant agreement (291734) and a European Molecular Biology Organization long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409), E. Kiermaier by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2151—390873048, and H. Hacker by the American Lebanese Syrian Associated ¨Charities. K.-D. Fischer was supported by the Analysis, Imaging and Modelling of Neuronal and Inflammatory Processes graduate school funded by the Ministry of Economics, Science, and Digitisation of the State Saxony-Anhalt and by the European Funds for Social and Regional Development.","pmid":1,"publisher":"Rockefeller University Press","article_processing_charge":"No","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"file":[{"relation":"main_file","date_updated":"2020-11-24T13:25:13Z","creator":"dernst","file_id":"8801","checksum":"cb0b9c77842ae1214caade7b77e4d82d","file_name":"2020_JCellBiol_Kopf.pdf","success":1,"content_type":"application/pdf","file_size":7536712,"date_created":"2020-11-24T13:25:13Z","access_level":"open_access"}],"publication_status":"published","oa_version":"Published Version","date_created":"2020-05-24T22:00:56Z","title":"Microtubules control cellular shape and coherence in amoeboid migrating cells","publication_identifier":{"eissn":["1540-8140"]},"isi":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"}],"publication":"The Journal of Cell Biology","date_updated":"2025-04-14T13:10:03Z","file_date_updated":"2020-11-24T13:25:13Z","scopus_import":"1","issue":"6","ec_funded":1,"status":"public","day":"01","citation":{"mla":"Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” <i>The Journal of Cell Biology</i>, vol. 219, no. 6, e201907154, Rockefeller University Press, 2020, doi:<a href=\"https://doi.org/10.1083/jcb.201907154\">10.1083/jcb.201907154</a>.","short":"A. Kopf, J. Renkawitz, R. Hauschild, I. Girkontaite, K. Tedford, J. Merrin, O. Thorn-Seshold, D. Trauner, H. Häcker, K.D. Fischer, E. Kiermaier, M.K. Sixt, The Journal of Cell Biology 219 (2020).","ieee":"A. Kopf <i>et al.</i>, “Microtubules control cellular shape and coherence in amoeboid migrating cells,” <i>The Journal of Cell Biology</i>, vol. 219, no. 6. Rockefeller University Press, 2020.","apa":"Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin, J., … Sixt, M. K. (2020). Microtubules control cellular shape and coherence in amoeboid migrating cells. <i>The Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.201907154\">https://doi.org/10.1083/jcb.201907154</a>","ama":"Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape and coherence in amoeboid migrating cells. <i>The Journal of Cell Biology</i>. 2020;219(6). doi:<a href=\"https://doi.org/10.1083/jcb.201907154\">10.1083/jcb.201907154</a>","ista":"Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt MK. 2020. Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. 219(6), e201907154.","chicago":"Kopf, Aglaja, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry Tedford, Jack Merrin, Oliver Thorn-Seshold, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” <i>The Journal of Cell Biology</i>. Rockefeller University Press, 2020. <a href=\"https://doi.org/10.1083/jcb.201907154\">https://doi.org/10.1083/jcb.201907154</a>."},"has_accepted_license":"1","quality_controlled":"1","type":"journal_article","external_id":{"isi":["000538141100020"],"pmid":["32379884"]},"_id":"7875","abstract":[{"text":"Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.","lang":"eng"}],"language":[{"iso":"eng"}],"date_published":"2020-06-01T00:00:00Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"year":"2020","article_number":"e201907154","intvolume":"       219"},{"doi":"10.1038/s41586-020-2283-z","oa":1,"acknowledgement":"We thank A. Leithner and J. Renkawitz for discussion and critical reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic setups; the Bioimaging Facility of IST Austria for excellent support, as well as the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan, L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme. This work was supported by the European Research Council (ERC StG 281556 and CoG 724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476). F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687.","author":[{"orcid":"0000-0003-0666-8928","id":"35B76592-F248-11E8-B48F-1D18A9856A87","first_name":"Anne","last_name":"Reversat","full_name":"Reversat, Anne"},{"orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","first_name":"Florian R","full_name":"Gärtner, Florian R","last_name":"Gärtner"},{"full_name":"Merrin, Jack","last_name":"Merrin","orcid":"0000-0001-5145-4609","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Stopp","full_name":"Stopp, Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","first_name":"Julian A"},{"last_name":"Tasciyan","full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","orcid":"0000-0003-1671-393X"},{"orcid":"0000-0002-2862-8372","first_name":"Juan L","id":"2A67C376-F248-11E8-B48F-1D18A9856A87","last_name":"Aguilera Servin","full_name":"Aguilera Servin, Juan L"},{"full_name":"De Vries, Ingrid","last_name":"De Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hons, Miroslav","last_name":"Hons","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","first_name":"Miroslav","orcid":"0000-0002-6625-3348"},{"first_name":"Matthieu","last_name":"Piel","full_name":"Piel, Matthieu"},{"first_name":"Andrew","last_name":"Callan-Jones","full_name":"Callan-Jones, Andrew"},{"last_name":"Voituriez","full_name":"Voituriez, Raphael","first_name":"Raphael"},{"last_name":"Sixt","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"}],"volume":582,"department":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"MiSi"}],"month":"06","article_type":"original","project":[{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"},{"grant_number":"724373","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular Navigation Along Spatial Gradients"},{"name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"}],"article_processing_charge":"No","publisher":"Springer Nature","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/"}],"record":[{"relation":"dissertation_contains","id":"14697","status":"public"},{"relation":"dissertation_contains","status":"public","id":"12401"}]},"pmid":1,"publication_status":"published","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"title":"Cellular locomotion using environmental topography","date_created":"2020-05-24T22:01:01Z","OA_type":"green","oa_version":"Preprint","publication":"Nature","date_updated":"2026-04-27T22:30:54Z","isi":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"status":"public","page":"582–585","ec_funded":1,"scopus_import":"1","external_id":{"isi":["000532688300008"],"pmid":["32581372"]},"_id":"7885","abstract":[{"lang":"eng","text":"Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour."}],"language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","day":"25","citation":{"chicago":"Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan, Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental Topography.” <i>Nature</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41586-020-2283-z\">https://doi.org/10.1038/s41586-020-2283-z</a>.","ama":"Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental topography. <i>Nature</i>. 2020;582:582–585. doi:<a href=\"https://doi.org/10.1038/s41586-020-2283-z\">10.1038/s41586-020-2283-z</a>","ista":"Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL, de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK. 2020. Cellular locomotion using environmental topography. Nature. 582, 582–585.","apa":"Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-020-2283-z\">https://doi.org/10.1038/s41586-020-2283-z</a>","mla":"Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.” <i>Nature</i>, vol. 582, Springer Nature, 2020, pp. 582–585, doi:<a href=\"https://doi.org/10.1038/s41586-020-2283-z\">10.1038/s41586-020-2283-z</a>.","short":"A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez, M.K. Sixt, Nature 582 (2020) 582–585.","ieee":"A. Reversat <i>et al.</i>, “Cellular locomotion using environmental topography,” <i>Nature</i>, vol. 582. Springer Nature, pp. 582–585, 2020."},"intvolume":"       582","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2020","OA_place":"repository","date_published":"2020-06-25T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1101/793919","open_access":"1"}]}]