[{"abstract":[{"lang":"eng","text":"Motile cells moving in multicellular organisms encounter microenvironments of locally heterogeneous mechanochemical composition. Individual compositional parameters like chemotactic signals, adhesiveness, and pore sizes are well known to be sensed by motile cells, providing individual guidance cues for cellular pathfinding. However, motile cells encounter diverse mechanochemical signals at the same time, raising the question of how cells respond to locally diverse and potentially competing signals on their migration routes. Here, we reveal that motile amoeboid cells require nuclear repositioning, termed nucleokinesis, for adaptive pathfinding in heterogeneous mechanochemical microenvironments. Using mammalian immune cells and the amoebaDictyostelium discoideum, we discover that frequent, rapid and long-distance nucleokinesis is a basic component of amoeboid pathfinding, enabling cells to reorientate quickly between locally competing cues. Amoeboid nucleokinesis comprises a two-step cell polarity switch and is driven by myosin II-forces, sliding the nucleus from a ‘losing’ to the ‘winning’ leading edge to re-adjust the nuclear to the cellular path. Impaired nucleokinesis distorts fast path adaptions and causes cellular arrest in the microenvironment. Our findings establish that nucleokinesis is required for amoeboid cell navigation. Given that motile single-cell amoebae, many immune cells, and some cancer cells utilize an amoeboid migration strategy, these results suggest that amoeboid nucleokinesis underlies cellular navigation during unicellular biology, immunity, and disease."}],"type":"journal_article","file":[{"file_name":"2023_EmboJournal_Kroll.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":4862497,"file_id":"14611","relation":"main_file","date_created":"2023-11-27T08:45:56Z","date_updated":"2023-11-27T08:45:56Z","success":1,"checksum":"6261d0041c7e8d284c39712c40079730"}],"oa_version":"Published Version","_id":"13342","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Adaptive pathfinding by nucleokinesis during amoeboid migration","status":"public","ddc":["570"],"has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","day":"21","scopus_import":"1","date_published":"2023-11-21T00:00:00Z","citation":{"chicago":"Kroll, Janina, Robert Hauschild, Arthur Kuznetcov, Kasia Stefanowski, Monika D. Hermann, Jack Merrin, Lubuna B Shafeek, Annette Müller-Taubenberger, and Jörg Renkawitz. “Adaptive Pathfinding by Nucleokinesis during Amoeboid Migration.” EMBO Journal. Embo Press, 2023. https://doi.org/10.15252/embj.2023114557.","short":"J. Kroll, R. Hauschild, A. Kuznetcov, K. Stefanowski, M.D. Hermann, J. Merrin, L.B. Shafeek, A. Müller-Taubenberger, J. Renkawitz, EMBO Journal (2023).","mla":"Kroll, Janina, et al. “Adaptive Pathfinding by Nucleokinesis during Amoeboid Migration.” EMBO Journal, e114557, Embo Press, 2023, doi:10.15252/embj.2023114557.","ieee":"J. Kroll et al., “Adaptive pathfinding by nucleokinesis during amoeboid migration,” EMBO Journal. Embo Press, 2023.","apa":"Kroll, J., Hauschild, R., Kuznetcov, A., Stefanowski, K., Hermann, M. D., Merrin, J., … Renkawitz, J. (2023). Adaptive pathfinding by nucleokinesis during amoeboid migration. EMBO Journal. Embo Press. https://doi.org/10.15252/embj.2023114557","ista":"Kroll J, Hauschild R, Kuznetcov A, Stefanowski K, Hermann MD, Merrin J, Shafeek LB, Müller-Taubenberger A, Renkawitz J. 2023. Adaptive pathfinding by nucleokinesis during amoeboid migration. EMBO Journal., e114557.","ama":"Kroll J, Hauschild R, Kuznetcov A, et al. Adaptive pathfinding by nucleokinesis during amoeboid migration. EMBO Journal. 2023. doi:10.15252/embj.2023114557"},"publication":"EMBO Journal","article_type":"original","file_date_updated":"2023-11-27T08:45:56Z","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","article_number":"e114557","author":[{"first_name":"Janina","last_name":"Kroll","full_name":"Kroll, Janina"},{"first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert"},{"full_name":"Kuznetcov, Arthur","first_name":"Arthur","last_name":"Kuznetcov"},{"full_name":"Stefanowski, Kasia","first_name":"Kasia","last_name":"Stefanowski"},{"full_name":"Hermann, Monika D.","last_name":"Hermann","first_name":"Monika D."},{"full_name":"Merrin, Jack","first_name":"Jack","last_name":"Merrin","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"last_name":"Shafeek","first_name":"Lubuna B","orcid":"0000-0001-7180-6050","id":"3CD37A82-F248-11E8-B48F-1D18A9856A87","full_name":"Shafeek, Lubuna B"},{"full_name":"Müller-Taubenberger, Annette","last_name":"Müller-Taubenberger","first_name":"Annette"},{"full_name":"Renkawitz, Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","first_name":"Jörg"}],"date_created":"2023-08-01T08:59:06Z","date_updated":"2023-11-27T08:47:45Z","pmid":1,"acknowledgement":"We thank Christoph Mayr and Bingzhi Wang for initial experiments on amoeboid nucleokinesis, Ana-Maria Lennon-Duménil and Aline Yatim for bone marrow from MyoIIA-Flox*CD11c-Cre mice, Michael Sixt and Aglaja Kopf for EMTB-mCherry, EB3-mCherry, Lifeact-GFP, Lfc knockout, and Myh9-GFP expressing HoxB8 cells, Malte Benjamin Braun, Mauricio Ruiz, and Madeleine T. Schmitt for critical reading of the manuscript, and the Core Facility Bioimaging, the Core Facility Flow Cytometry, and the Animal Core Facility of the Biomedical Center (BMC) for excellent support. This study was supported by the Peter Hans Hofschneider Professorship of the foundation “Stiftung Experimentelle Biomedizin” (to JR), the LMU Institutional Strategy LMU-Excellent within the framework of the German Excellence Initiative (to JR), and the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; SFB914 project A12, to JR), and the CZI grant DAF2020-225401 (https://doi.org/10.37921/120055ratwvi) from the Chan Zuckerberg Initiative DAF (to RH; an advised fund of Silicon Valley Community Foundation (funder https://doi.org/10.13039/100014989)). Open Access funding enabled and organized by Projekt DEAL.","year":"2023","publisher":"Embo Press","department":[{"_id":"NanoFab"},{"_id":"Bio"}],"publication_status":"published","publication_identifier":{"eissn":["1460-2075"],"issn":["0261-4189"]},"month":"11","doi":"10.15252/embj.2023114557","language":[{"iso":"eng"}],"tmp":{"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","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"pmid":["37987147"]},"oa":1,"quality_controlled":"1"},{"ddc":["570"],"status":"public","title":"Quantifying the probing and selection of microenvironmental pores by motile immune cells","intvolume":" 2","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11182","oa_version":"Published Version","file":[{"file_size":2142703,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2022_CurrentProtocols_Kroll.pdf","checksum":"72152d005c367777f6cf2f6a477f0d52","success":1,"date_updated":"2022-05-02T08:16:10Z","date_created":"2022-05-02T08:16:10Z","relation":"main_file","file_id":"11347"}],"type":"journal_article","abstract":[{"text":"Immune cells are constantly on the move through multicellular organisms to explore and respond to pathogens and other harmful insults. While moving, immune cells efficiently traverse microenvironments composed of tissue cells and extracellular fibers, which together form complex environments of various porosity, stiffness, topography, and chemical composition. In this protocol we describe experimental procedures to investigate immune cell migration through microenvironments of heterogeneous porosity. In particular, we describe micro-channels, micro-pillars, and collagen networks as cell migration paths with alternative pore size choices. Employing micro-channels or micro-pillars that divide at junctions into alternative paths with initially differentially sized pores allows us to precisely (1) measure the cellular translocation time through these porous path junctions, (2) quantify the cellular preference for individual pore sizes, and (3) image cellular components like the nucleus and the cytoskeleton. This reductionistic experimental setup thus can elucidate how immune cells perform decisions in complex microenvironments of various porosity like the interstitium. The setup further allows investigation of the underlying forces of cellular squeezing and the consequences of cellular deformation on the integrity of the cell and its organelles. As a complementary approach that does not require any micro-engineering expertise, we describe the usage of three-dimensional collagen networks with different pore sizes. Whereas we here focus on dendritic cells as a model for motile immune cells, the described protocols are versatile as they are also applicable for other immune cell types like neutrophils and non-immune cell types such as mesenchymal and cancer cells. In summary, we here describe protocols to identify the mechanisms and principles of cellular probing, decision making, and squeezing during cellular movement through microenvironments of heterogeneous porosity.","lang":"eng"}],"issue":"4","article_type":"original","publication":"Current Protocols","citation":{"chicago":"Kroll, Janina, Mauricio J.A. Ruiz-Fernandez, Malte B. Braun, Jack Merrin, and Jörg Renkawitz. “Quantifying the Probing and Selection of Microenvironmental Pores by Motile Immune Cells.” Current Protocols. Wiley, 2022. https://doi.org/10.1002/cpz1.407.","short":"J. Kroll, M.J.A. Ruiz-Fernandez, M.B. Braun, J. Merrin, J. Renkawitz, Current Protocols 2 (2022).","mla":"Kroll, Janina, et al. “Quantifying the Probing and Selection of Microenvironmental Pores by Motile Immune Cells.” Current Protocols, vol. 2, no. 4, e407, Wiley, 2022, doi:10.1002/cpz1.407.","ieee":"J. Kroll, M. J. A. Ruiz-Fernandez, M. B. Braun, J. Merrin, and J. Renkawitz, “Quantifying the probing and selection of microenvironmental pores by motile immune cells,” Current Protocols, vol. 2, no. 4. Wiley, 2022.","apa":"Kroll, J., Ruiz-Fernandez, M. J. A., Braun, M. B., Merrin, J., & Renkawitz, J. (2022). Quantifying the probing and selection of microenvironmental pores by motile immune cells. Current Protocols. Wiley. https://doi.org/10.1002/cpz1.407","ista":"Kroll J, Ruiz-Fernandez MJA, Braun MB, Merrin J, Renkawitz J. 2022. Quantifying the probing and selection of microenvironmental pores by motile immune cells. Current Protocols. 2(4), e407.","ama":"Kroll J, Ruiz-Fernandez MJA, Braun MB, Merrin J, Renkawitz J. Quantifying the probing and selection of microenvironmental pores by motile immune cells. Current Protocols. 2022;2(4). doi:10.1002/cpz1.407"},"date_published":"2022-04-05T00:00:00Z","scopus_import":"1","day":"05","has_accepted_license":"1","article_processing_charge":"No","publication_status":"published","publisher":"Wiley","department":[{"_id":"NanoFab"}],"year":"2022","acknowledgement":"We thank Kasia Stefanowski for excellent technical assistance, and the Core Facility Bioimaging of the Biomedical Center (BMC) of the Ludwig-Maximilian University for excellent support. We gratefully acknowledge financial support from the Peter Hans Hofschneider Professorship of the Stiftung Experimentelle Biomedizin (to J.R), from the DFG (Collaborative Research Center SFB914, project A12; and Priority Programme SPP2332, project 492014049; both to J.R) and from the LMU Institutional Strategy LMU-Excellent within the framework of the German Excellence Initiative (to J.R).\r\nOpen access funding enabled and organized by Projekt DEAL.","pmid":1,"date_updated":"2022-05-02T08:18:00Z","date_created":"2022-04-17T22:01:46Z","volume":2,"author":[{"last_name":"Kroll","first_name":"Janina","full_name":"Kroll, Janina"},{"first_name":"Mauricio J.A.","last_name":"Ruiz-Fernandez","full_name":"Ruiz-Fernandez, Mauricio J.A."},{"full_name":"Braun, Malte B.","last_name":"Braun","first_name":"Malte B."},{"full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","first_name":"Jack"},{"orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","first_name":"Jörg","full_name":"Renkawitz, Jörg"}],"article_number":"e407","license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2022-05-02T08:16:10Z","quality_controlled":"1","oa":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"},"external_id":{"pmid":["35384410"]},"language":[{"iso":"eng"}],"doi":"10.1002/cpz1.407","month":"04","publication_identifier":{"eissn":["2691-1299"]}},{"issue":"6","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"}],"type":"journal_article","oa_version":"Published Version","file":[{"file_id":"8801","relation":"main_file","date_created":"2020-11-24T13:25:13Z","date_updated":"2020-11-24T13:25:13Z","success":1,"checksum":"cb0b9c77842ae1214caade7b77e4d82d","file_name":"2020_JCellBiol_Kopf.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":7536712}],"_id":"7875","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 219","title":"Microtubules control cellular shape and coherence in amoeboid migrating cells","status":"public","ddc":["570"],"article_processing_charge":"No","has_accepted_license":"1","day":"01","scopus_import":"1","date_published":"2020-06-01T00:00:00Z","citation":{"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.” The Journal of Cell Biology. Rockefeller University Press, 2020. https://doi.org/10.1083/jcb.201907154.","mla":"Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” The Journal of Cell Biology, vol. 219, no. 6, e201907154, Rockefeller University Press, 2020, doi:10.1083/jcb.201907154.","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).","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.","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. The Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.201907154","ieee":"A. Kopf et al., “Microtubules control cellular shape and coherence in amoeboid migrating cells,” The Journal of Cell Biology, vol. 219, no. 6. Rockefeller University Press, 2020.","ama":"Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. 2020;219(6). doi:10.1083/jcb.201907154"},"publication":"The Journal of Cell Biology","article_type":"original","ec_funded":1,"file_date_updated":"2020-11-24T13:25:13Z","article_number":"e201907154","author":[{"first_name":"Aglaja","last_name":"Kopf","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja"},{"orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","first_name":"Jörg","full_name":"Renkawitz, Jörg"},{"first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert"},{"first_name":"Irute","last_name":"Girkontaite","full_name":"Girkontaite, Irute"},{"last_name":"Tedford","first_name":"Kerry","full_name":"Tedford, Kerry"},{"full_name":"Merrin, Jack","first_name":"Jack","last_name":"Merrin","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"last_name":"Thorn-Seshold","first_name":"Oliver","full_name":"Thorn-Seshold, Oliver"},{"last_name":"Trauner","first_name":"Dirk","id":"E8F27F48-3EBA-11E9-92A1-B709E6697425","full_name":"Trauner, Dirk"},{"full_name":"Häcker, Hans","first_name":"Hans","last_name":"Häcker"},{"full_name":"Fischer, Klaus Dieter","last_name":"Fischer","first_name":"Klaus Dieter"},{"orcid":"0000-0001-6165-5738","id":"3EB04B78-F248-11E8-B48F-1D18A9856A87","last_name":"Kiermaier","first_name":"Eva","full_name":"Kiermaier, Eva"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"volume":219,"date_updated":"2023-08-21T06:28:17Z","date_created":"2020-05-24T22:00:56Z","pmid":1,"year":"2020","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.","publisher":"Rockefeller University Press","department":[{"_id":"MiSi"},{"_id":"Bio"},{"_id":"NanoFab"}],"publication_status":"published","publication_identifier":{"eissn":["1540-8140"]},"month":"06","doi":"10.1083/jcb.201907154","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"}],"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,"external_id":{"isi":["000538141100020"],"pmid":["32379884"]},"project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7"},{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","call_identifier":"H2020","name":"Cellular navigation along spatial gradients"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911","call_identifier":"FWF","name":"Mechanical adaptation of lamellipodial actin"},{"name":"Nano-Analytics of Cellular Systems","call_identifier":"FWF","_id":"252C3B08-B435-11E9-9278-68D0E5697425","grant_number":"W 1250-B20"},{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"name":"Molecular and system level view of immune cell migration","grant_number":"ALTF 1396-2014","_id":"25A48D24-B435-11E9-9278-68D0E5697425"}],"isi":1,"quality_controlled":"1"},{"article_processing_charge":"No","day":"25","scopus_import":"1","date_published":"2019-04-25T00:00:00Z","citation":{"chicago":"Renkawitz, Jörg, Aglaja Kopf, Julian A Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature. Springer Nature, 2019. https://doi.org/10.1038/s41586-019-1087-5.","mla":"Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature, vol. 568, Springer Nature, 2019, pp. 546–50, doi:10.1038/s41586-019-1087-5.","short":"J. Renkawitz, A. Kopf, J.A. Stopp, I. de Vries, M.K. Driscoll, J. Merrin, R. Hauschild, E.S. Welf, G. Danuser, R. Fiolka, M.K. Sixt, Nature 568 (2019) 546–550.","ista":"Renkawitz J, Kopf A, Stopp JA, de Vries I, Driscoll MK, Merrin J, Hauschild R, Welf ES, Danuser G, Fiolka R, Sixt MK. 2019. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 568, 546–550.","apa":"Renkawitz, J., Kopf, A., Stopp, J. A., de Vries, I., Driscoll, M. K., Merrin, J., … Sixt, M. K. (2019). Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1087-5","ieee":"J. Renkawitz et al., “Nuclear positioning facilitates amoeboid migration along the path of least resistance,” Nature, vol. 568. Springer Nature, pp. 546–550, 2019.","ama":"Renkawitz J, Kopf A, Stopp JA, et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 2019;568:546-550. doi:10.1038/s41586-019-1087-5"},"publication":"Nature","page":"546-550","article_type":"letter_note","abstract":[{"text":"During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion.","lang":"eng"}],"type":"journal_article","oa_version":"Submitted Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6328","intvolume":" 568","status":"public","title":"Nuclear positioning facilitates amoeboid migration along the path of least resistance","month":"04","doi":"10.1038/s41586-019-1087-5","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"oa":1,"external_id":{"isi":["000465594200050"],"pmid":["30944468"]},"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/","open_access":"1"}],"project":[{"grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)"},{"name":"Cellular navigation along spatial gradients","call_identifier":"H2020","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"grant_number":"W01250-B20","_id":"265FAEBA-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Nano-Analytics of Cellular Systems"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014","name":"Molecular and system level view of immune cell migration"}],"isi":1,"quality_controlled":"1","ec_funded":1,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/","relation":"press_release","description":"News on IST Homepage"}],"record":[{"id":"14697","status":"public","relation":"dissertation_contains"},{"id":"6891","status":"public","relation":"dissertation_contains"}]},"author":[{"orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","first_name":"Jörg","full_name":"Renkawitz, Jörg"},{"full_name":"Kopf, Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656","first_name":"Aglaja","last_name":"Kopf"},{"id":"489E3F00-F248-11E8-B48F-1D18A9856A87","first_name":"Julian A","last_name":"Stopp","full_name":"Stopp, Julian A"},{"first_name":"Ingrid","last_name":"de Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"de Vries, Ingrid"},{"full_name":"Driscoll, Meghan K.","first_name":"Meghan K.","last_name":"Driscoll"},{"first_name":"Jack","last_name":"Merrin","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Welf, Erik S.","last_name":"Welf","first_name":"Erik S."},{"first_name":"Gaudenz","last_name":"Danuser","full_name":"Danuser, Gaudenz"},{"full_name":"Fiolka, Reto","last_name":"Fiolka","first_name":"Reto"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"volume":568,"date_updated":"2024-03-28T23:30:40Z","date_created":"2019-04-17T06:52:28Z","pmid":1,"year":"2019","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"publisher":"Springer Nature","publication_status":"published"},{"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"oa":1,"external_id":{"isi":["000434963700016"]},"isi":1,"quality_controlled":"1","project":[{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"doi":"10.1002/eji.201747358","acknowledged_ssus":[{"_id":"SSU"}],"language":[{"iso":"eng"}],"month":"02","year":"2018","acknowledgement":"This work was supported by grants of the European Research Council (ERC CoG 724373) and the Austrian Science Fund (FWF) to M.S. We thank the scientific support units at IST Austria for excellent technical support.\r\nWe thank the scientific support units at IST Austria for excellent technical support. ","publication_status":"published","department":[{"_id":"MiSi"},{"_id":"Bio"}],"publisher":"Wiley-Blackwell","author":[{"last_name":"Leithner","first_name":"Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"full_name":"Renkawitz, Jörg","last_name":"Renkawitz","first_name":"Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","last_name":"De Vries","first_name":"Ingrid"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Haecker","first_name":"Hans","full_name":"Haecker, Hans"},{"last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"date_created":"2018-12-11T11:46:28Z","date_updated":"2023-09-11T14:01:18Z","volume":48,"file_date_updated":"2020-07-14T12:46:27Z","ec_funded":1,"publist_id":"7386","license":"https://creativecommons.org/licenses/by-nc/4.0/","publication":"European Journal of Immunology","citation":{"short":"A.F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, M.K. Sixt, European Journal of Immunology 48 (2018) 1074–1077.","mla":"Leithner, Alexander F., et al. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” European Journal of Immunology, vol. 48, no. 6, Wiley-Blackwell, 2018, pp. 1074–77, doi:10.1002/eji.201747358.","chicago":"Leithner, Alexander F, Jörg Renkawitz, Ingrid de Vries, Robert Hauschild, Hans Haecker, and Michael K Sixt. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” European Journal of Immunology. Wiley-Blackwell, 2018. https://doi.org/10.1002/eji.201747358.","ama":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. 2018;48(6):1074-1077. doi:10.1002/eji.201747358","ieee":"A. F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, and M. K. Sixt, “Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration,” European Journal of Immunology, vol. 48, no. 6. Wiley-Blackwell, pp. 1074–1077, 2018.","apa":"Leithner, A. F., Renkawitz, J., de Vries, I., Hauschild, R., Haecker, H., & Sixt, M. K. (2018). Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. Wiley-Blackwell. https://doi.org/10.1002/eji.201747358","ista":"Leithner AF, Renkawitz J, de Vries I, Hauschild R, Haecker H, Sixt MK. 2018. Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. European Journal of Immunology. 48(6), 1074–1077."},"page":"1074 - 1077","date_published":"2018-02-13T00:00:00Z","scopus_import":"1","day":"13","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"437","ddc":["570"],"title":"Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration","status":"public","intvolume":" 48","pubrep_id":"1067","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5044","checksum":"9d5b74cd016505aeb9a4c2d33bbedaeb","date_updated":"2020-07-14T12:46:27Z","date_created":"2018-12-12T10:13:56Z","access_level":"open_access","file_name":"IST-2018-1067-v1+2_Leithner_et_al-2018-European_Journal_of_Immunology.pdf","content_type":"application/pdf","file_size":590106,"creator":"system"}],"type":"journal_article","abstract":[{"text":"Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity.","lang":"eng"}],"issue":"6"},{"type":"book_chapter","abstract":[{"text":"Cells migrating in multicellular organisms steadily traverse complex three-dimensional (3D) environments. To decipher the underlying cell biology, current experimental setups either use simplified 2D, tissue-mimetic 3D (e.g., collagen matrices) or in vivo environments. While only in vivo experiments are truly physiological, they do not allow for precise manipulation of environmental parameters. 2D in vitro experiments do allow mechanical and chemical manipulations, but increasing evidence demonstrates substantial differences of migratory mechanisms in 2D and 3D. Here, we describe simple, robust, and versatile “pillar forests” to investigate cell migration in complex but fully controllable 3D environments. Pillar forests are polydimethylsiloxane-based setups, in which two closely adjacent surfaces are interconnected by arrays of micrometer-sized pillars. Changing the pillar shape, size, height and the inter-pillar distance precisely manipulates microenvironmental parameters (e.g., pore sizes, micro-geometry, micro-topology), while being easily combined with chemotactic cues, surface coatings, diverse cell types and advanced imaging techniques. Thus, pillar forests combine the advantages of 2D cell migration assays with the precise definition of 3D environmental parameters.","lang":"eng"}],"_id":"153","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","title":"Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments","intvolume":" 147","oa_version":"None","scopus_import":"1","day":"27","article_processing_charge":"No","publication":"Methods in Cell Biology","citation":{"ista":"Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. 2018.Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: Methods in Cell Biology. vol. 147, 79–91.","ieee":"J. Renkawitz, A. Reversat, A. F. Leithner, J. Merrin, and M. K. Sixt, “Micro-engineered ‘pillar forests’ to study cell migration in complex but controlled 3D environments,” in Methods in Cell Biology, vol. 147, Academic Press, 2018, pp. 79–91.","apa":"Renkawitz, J., Reversat, A., Leithner, A. F., Merrin, J., & Sixt, M. K. (2018). Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In Methods in Cell Biology (Vol. 147, pp. 79–91). Academic Press. https://doi.org/10.1016/bs.mcb.2018.07.004","ama":"Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: Methods in Cell Biology. Vol 147. Academic Press; 2018:79-91. doi:10.1016/bs.mcb.2018.07.004","chicago":"Renkawitz, Jörg, Anne Reversat, Alexander F Leithner, Jack Merrin, and Michael K Sixt. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” In Methods in Cell Biology, 147:79–91. Academic Press, 2018. https://doi.org/10.1016/bs.mcb.2018.07.004.","mla":"Renkawitz, Jörg, et al. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” Methods in Cell Biology, vol. 147, Academic Press, 2018, pp. 79–91, doi:10.1016/bs.mcb.2018.07.004.","short":"J. Renkawitz, A. Reversat, A.F. Leithner, J. Merrin, M.K. Sixt, in:, Methods in Cell Biology, Academic Press, 2018, pp. 79–91."},"page":"79 - 91","date_published":"2018-07-27T00:00:00Z","publist_id":"7768","year":"2018","pmid":1,"publication_status":"published","publisher":"Academic Press","department":[{"_id":"MiSi"},{"_id":"NanoFab"}],"author":[{"first_name":"Jörg","last_name":"Renkawitz","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","full_name":"Renkawitz, Jörg"},{"full_name":"Reversat, Anne","orcid":"0000-0003-0666-8928","id":"35B76592-F248-11E8-B48F-1D18A9856A87","last_name":"Reversat","first_name":"Anne"},{"full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","first_name":"Alexander F"},{"full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","first_name":"Jack"},{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"date_updated":"2023-09-13T08:56:35Z","date_created":"2018-12-11T11:44:54Z","volume":147,"month":"07","publication_identifier":{"issn":["0091679X"]},"external_id":{"isi":["000452412300006"],"pmid":["30165964"]},"isi":1,"quality_controlled":"1","doi":"10.1016/bs.mcb.2018.07.004","language":[{"iso":"eng"}]},{"volume":13,"date_updated":"2023-09-13T09:00:15Z","date_created":"2018-12-11T11:45:34Z","author":[{"full_name":"Frick, Corina","last_name":"Frick","first_name":"Corina"},{"full_name":"Dettinger, Philip","last_name":"Dettinger","first_name":"Philip"},{"id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","first_name":"Jörg","last_name":"Renkawitz","full_name":"Renkawitz, Jörg"},{"last_name":"Jauch","first_name":"Annaïse","full_name":"Jauch, Annaïse"},{"full_name":"Berger, Christoph","first_name":"Christoph","last_name":"Berger"},{"first_name":"Mike","last_name":"Recher","full_name":"Recher, Mike"},{"last_name":"Schroeder","first_name":"Timm","full_name":"Schroeder, Timm"},{"first_name":"Matthias","last_name":"Mehling","full_name":"Mehling, Matthias"}],"publisher":"Public Library of Science","department":[{"_id":"MiSi"}],"publication_status":"published","year":"2018","acknowledgement":"This work was supported by the Swiss National Science Foundation (MD-PhD fellowships, 323530_164221 to C.F.; and 323630_151483 to A.J.; grant PZ00P3_144863 to M.R, grant 31003A_156431 to T.S.; PZ00P3_148000 to C.T.B.; PZ00P3_154733 to M.M.), a Novartis “FreeNovation” grant to M.M. and T.S. and an EMBO long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409) to J.R.. M.R. was supported by the Gebert Rüf Foundation (GRS 058/14). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","publist_id":"7626","file_date_updated":"2020-07-14T12:45:45Z","article_number":"e0198330","language":[{"iso":"eng"}],"doi":"10.1371/journal.pone.0198330","isi":1,"quality_controlled":"1","external_id":{"isi":["000434384900031"]},"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,"month":"06","file":[{"date_updated":"2020-07-14T12:45:45Z","date_created":"2018-12-17T14:10:32Z","checksum":"95fc5dc3938b3ad3b7697d10c83cc143","file_id":"5709","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":7682167,"file_name":"2018_Plos_Frick.pdf","access_level":"open_access"}],"oa_version":"Published Version","intvolume":" 13","title":"Nano-scale microfluidics to study 3D chemotaxis at the single cell level","ddc":["570"],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"276","issue":"6","abstract":[{"lang":"eng","text":"Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controlla-bility of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion-based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL19 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo."}],"type":"journal_article","date_published":"2018-06-07T00:00:00Z","article_type":"original","citation":{"chicago":"Frick, Corina, Philip Dettinger, Jörg Renkawitz, Annaïse Jauch, Christoph Berger, Mike Recher, Timm Schroeder, and Matthias Mehling. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” PLoS One. Public Library of Science, 2018. https://doi.org/10.1371/journal.pone.0198330.","short":"C. Frick, P. Dettinger, J. Renkawitz, A. Jauch, C. Berger, M. Recher, T. Schroeder, M. Mehling, PLoS One 13 (2018).","mla":"Frick, Corina, et al. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” PLoS One, vol. 13, no. 6, e0198330, Public Library of Science, 2018, doi:10.1371/journal.pone.0198330.","ieee":"C. Frick et al., “Nano-scale microfluidics to study 3D chemotaxis at the single cell level,” PLoS One, vol. 13, no. 6. Public Library of Science, 2018.","apa":"Frick, C., Dettinger, P., Renkawitz, J., Jauch, A., Berger, C., Recher, M., … Mehling, M. (2018). Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0198330","ista":"Frick C, Dettinger P, Renkawitz J, Jauch A, Berger C, Recher M, Schroeder T, Mehling M. 2018. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. 13(6), e0198330.","ama":"Frick C, Dettinger P, Renkawitz J, et al. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. 2018;13(6). doi:10.1371/journal.pone.0198330"},"publication":"PLoS One","has_accepted_license":"1","article_processing_charge":"No","day":"07","scopus_import":"1"},{"day":"18","article_processing_charge":"No","scopus_import":"1","date_published":"2018-05-18T00:00:00Z","publication":"Nature Immunology","citation":{"ama":"Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 2018;19(6):606-616. doi:10.1038/s41590-018-0109-z","apa":"Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J., … Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/s41590-018-0109-z","ieee":"M. Hons et al., “Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells,” Nature Immunology, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.","ista":"Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J, Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 19(6), 606–616.","short":"M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz, J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616.","mla":"Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology, vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:10.1038/s41590-018-0109-z.","chicago":"Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology. Nature Publishing Group, 2018. https://doi.org/10.1038/s41590-018-0109-z."},"page":"606 - 616","abstract":[{"text":"Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux.","lang":"eng"}],"issue":"6","type":"journal_article","oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"15","status":"public","title":"Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells","intvolume":" 19","month":"05","doi":"10.1038/s41590-018-0109-z","acknowledged_ssus":[{"_id":"SSU"}],"language":[{"iso":"eng"}],"external_id":{"pmid":["29777221"],"isi":["000433041500026"]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/29777221"}],"oa":1,"isi":1,"quality_controlled":"1","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular navigation along spatial gradients","call_identifier":"H2020"},{"_id":"260AA4E2-B435-11E9-9278-68D0E5697425","grant_number":"747687","call_identifier":"H2020","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"},{"_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014","name":"Molecular and system level view of immune cell migration"},{"grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7"}],"publist_id":"8040","ec_funded":1,"author":[{"full_name":"Hons, Miroslav","last_name":"Hons","first_name":"Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","last_name":"Kopf","first_name":"Aglaja","full_name":"Kopf, Aglaja"},{"first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"id":"397A88EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6120-3723","first_name":"Florian R","last_name":"Gärtner","full_name":"Gärtner, Florian R"},{"last_name":"Abe","first_name":"Jun","full_name":"Abe, Jun"},{"id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","first_name":"Jörg","last_name":"Renkawitz","full_name":"Renkawitz, Jörg"},{"full_name":"Stein, Jens","last_name":"Stein","first_name":"Jens"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6891"}]},"date_created":"2018-12-11T11:44:10Z","date_updated":"2024-03-28T23:30:40Z","volume":19,"year":"2018","acknowledgement":"This work was funded by grants from the European Research Council (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S. and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457 and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014).","pmid":1,"publication_status":"published","department":[{"_id":"MiSi"},{"_id":"Bio"}],"publisher":"Nature Publishing Group"},{"date_published":"2017-05-16T00:00:00Z","page":"1294 - 1303","citation":{"chicago":"Lademann, Claudio, Jörg Renkawitz, Boris Pfander, and Stefan Jentsch. “The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during Homologous Recombination.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2017.04.051.","mla":"Lademann, Claudio, et al. “The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during Homologous Recombination.” Cell Reports, vol. 19, no. 7, Cell Press, 2017, pp. 1294–303, doi:10.1016/j.celrep.2017.04.051.","short":"C. Lademann, J. Renkawitz, B. Pfander, S. Jentsch, Cell Reports 19 (2017) 1294–1303.","ista":"Lademann C, Renkawitz J, Pfander B, Jentsch S. 2017. The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination. Cell Reports. 19(7), 1294–1303.","ieee":"C. Lademann, J. Renkawitz, B. Pfander, and S. Jentsch, “The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination,” Cell Reports, vol. 19, no. 7. Cell Press, pp. 1294–1303, 2017.","apa":"Lademann, C., Renkawitz, J., Pfander, B., & Jentsch, S. (2017). The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2017.04.051","ama":"Lademann C, Renkawitz J, Pfander B, Jentsch S. The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination. Cell Reports. 2017;19(7):1294-1303. doi:10.1016/j.celrep.2017.04.051"},"publication":"Cell Reports","has_accepted_license":"1","day":"16","scopus_import":1,"file":[{"relation":"main_file","file_id":"5171","checksum":"efc7287d9c6354983cb151880e9ad72a","date_updated":"2020-07-14T12:47:40Z","date_created":"2018-12-12T10:15:48Z","access_level":"open_access","file_name":"IST-2017-899-v1+1_1-s2.0-S2211124717305454-main.pdf","content_type":"application/pdf","file_size":3005610,"creator":"system"}],"oa_version":"Published Version","pubrep_id":"899","intvolume":" 19","ddc":["570"],"title":"The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination","status":"public","_id":"677","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"7","abstract":[{"lang":"eng","text":"The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR—DNA end resection and presynaptic filament formation. Importantly, the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR."}],"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.celrep.2017.04.051","quality_controlled":"1","oa":1,"tmp":{"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","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"publication_identifier":{"issn":["22111247"]},"month":"05","volume":19,"date_created":"2018-12-11T11:47:52Z","date_updated":"2021-01-12T08:08:57Z","author":[{"full_name":"Lademann, Claudio","last_name":"Lademann","first_name":"Claudio"},{"full_name":"Renkawitz, Jörg","first_name":"Jörg","last_name":"Renkawitz","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369"},{"full_name":"Pfander, Boris","first_name":"Boris","last_name":"Pfander"},{"full_name":"Jentsch, Stefan","last_name":"Jentsch","first_name":"Stefan"}],"publisher":"Cell Press","department":[{"_id":"MiSi"}],"publication_status":"published","year":"2017","publist_id":"7046","file_date_updated":"2020-07-14T12:47:40Z"},{"date_updated":"2021-01-12T06:48:39Z","date_created":"2018-12-11T11:50:25Z","volume":38,"oa_version":"None","author":[{"full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","first_name":"Jörg","last_name":"Renkawitz"},{"last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"status":"public","publication_status":"published","title":"A Radical Break Restraining Neutrophil Migration","intvolume":" 38","publisher":"Cell Press","department":[{"_id":"MiSi"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1150","year":"2016","abstract":[{"lang":"eng","text":"When neutrophils infiltrate a site of inflammation, they have to stop at the right place to exert their effector function. In this issue of Developmental Cell, Wang et al. (2016) show that neutrophils sense reactive oxygen species via the TRPM2 channel to arrest migration at their target site. © 2016 Elsevier Inc."}],"issue":"5","publist_id":"6208","type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.devcel.2016.08.017","date_published":"2016-09-12T00:00:00Z","quality_controlled":"1","page":"448 - 450","publication":"Developmental Cell","citation":{"ieee":"J. Renkawitz and M. K. Sixt, “A Radical Break Restraining Neutrophil Migration,” Developmental Cell, vol. 38, no. 5. Cell Press, pp. 448–450, 2016.","apa":"Renkawitz, J., & Sixt, M. K. (2016). A Radical Break Restraining Neutrophil Migration. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2016.08.017","ista":"Renkawitz J, Sixt MK. 2016. A Radical Break Restraining Neutrophil Migration. Developmental Cell. 38(5), 448–450.","ama":"Renkawitz J, Sixt MK. A Radical Break Restraining Neutrophil Migration. Developmental Cell. 2016;38(5):448-450. doi:10.1016/j.devcel.2016.08.017","chicago":"Renkawitz, Jörg, and Michael K Sixt. “A Radical Break Restraining Neutrophil Migration.” Developmental Cell. Cell Press, 2016. https://doi.org/10.1016/j.devcel.2016.08.017.","short":"J. Renkawitz, M.K. Sixt, Developmental Cell 38 (2016) 448–450.","mla":"Renkawitz, Jörg, and Michael K. Sixt. “A Radical Break Restraining Neutrophil Migration.” Developmental Cell, vol. 38, no. 5, Cell Press, 2016, pp. 448–50, doi:10.1016/j.devcel.2016.08.017."},"day":"12","month":"09","scopus_import":1},{"month":"12","day":"01","scopus_import":1,"doi":"10.1016/j.cell.2016.11.024","date_published":"2016-12-01T00:00:00Z","language":[{"iso":"eng"}],"publication":"Cell","citation":{"chicago":"Renkawitz, Jörg, and Michael K Sixt. “Formin’ a Nuclear Protection.” Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.024.","mla":"Renkawitz, Jörg, and Michael K. Sixt. “Formin’ a Nuclear Protection.” Cell, vol. 167, no. 6, Cell Press, 2016, pp. 1448–49, doi:10.1016/j.cell.2016.11.024.","short":"J. Renkawitz, M.K. Sixt, Cell 167 (2016) 1448–1449.","ista":"Renkawitz J, Sixt MK. 2016. Formin’ a nuclear protection. Cell. 167(6), 1448–1449.","apa":"Renkawitz, J., & Sixt, M. K. (2016). Formin’ a nuclear protection. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.024","ieee":"J. Renkawitz and M. K. Sixt, “Formin’ a nuclear protection,” Cell, vol. 167, no. 6. Cell Press, pp. 1448–1449, 2016.","ama":"Renkawitz J, Sixt MK. Formin’ a nuclear protection. Cell. 2016;167(6):1448-1449. doi:10.1016/j.cell.2016.11.024"},"quality_controlled":"1","page":"1448 - 1449","abstract":[{"lang":"eng","text":"In this issue of Cell, Skau et al. show that the formin FMN2 organizes a perinuclear actin cytoskeleton that protects the nucleus and its genomic content of migrating cells squeezing through small spaces."}],"issue":"6","publist_id":"6149","type":"journal_article","author":[{"first_name":"Jörg","last_name":"Renkawitz","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","full_name":"Renkawitz, Jörg"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"date_created":"2018-12-11T11:50:41Z","date_updated":"2021-01-12T06:49:03Z","volume":167,"oa_version":"None","_id":"1201","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","year":"2016","title":"Formin’ a nuclear protection","publication_status":"published","status":"public","publisher":"Cell Press","intvolume":" 167","department":[{"_id":"MiSi"}]},{"type":"journal_article","abstract":[{"lang":"eng","text":"Homologous recombination is crucial for genome stability and for genetic exchange. Although our knowledge of the principle steps in recombination and its machinery is well advanced, homology search, the critical step of exploring the genome for homologous sequences to enable recombination, has remained mostly enigmatic. However, recent methodological advances have provided considerable new insights into this fundamental step in recombination that can be integrated into a mechanistic model. These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process. They also aid our understanding of how homology search might lead to unwanted and potentially disease-promoting recombination events."}],"publist_id":"4755","issue":"6","status":"public","publication_status":"published","title":"Mechanisms and principles of homology search during recombination","publisher":"Nature Publishing Group","department":[{"_id":"MiSi"}],"intvolume":" 15","_id":"2215","year":"2014","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","acknowledgement":"J.R. was supported by a Boehringer Ingelheim Fonds PhD stipend.","date_created":"2018-12-11T11:56:22Z","date_updated":"2021-01-12T06:56:03Z","oa_version":"None","volume":15,"author":[{"full_name":"Renkawitz, Jörg","last_name":"Renkawitz","first_name":"Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lademann, Claudio","first_name":"Claudio","last_name":"Lademann"},{"full_name":"Jentsch, Stefan","last_name":"Jentsch","first_name":"Stefan"}],"scopus_import":1,"day":"14","month":"05","quality_controlled":"1","page":"369 - 383","publication":"Nature Reviews Molecular Cell Biology","citation":{"ama":"Renkawitz J, Lademann C, Jentsch S. Mechanisms and principles of homology search during recombination. Nature Reviews Molecular Cell Biology. 2014;15(6):369-383. doi:10.1038/nrm3805","ieee":"J. Renkawitz, C. Lademann, and S. Jentsch, “Mechanisms and principles of homology search during recombination,” Nature Reviews Molecular Cell Biology, vol. 15, no. 6. Nature Publishing Group, pp. 369–383, 2014.","apa":"Renkawitz, J., Lademann, C., & Jentsch, S. (2014). Mechanisms and principles of homology search during recombination. Nature Reviews Molecular Cell Biology. Nature Publishing Group. https://doi.org/10.1038/nrm3805","ista":"Renkawitz J, Lademann C, Jentsch S. 2014. Mechanisms and principles of homology search during recombination. Nature Reviews Molecular Cell Biology. 15(6), 369–383.","short":"J. Renkawitz, C. Lademann, S. Jentsch, Nature Reviews Molecular Cell Biology 15 (2014) 369–383.","mla":"Renkawitz, Jörg, et al. “Mechanisms and Principles of Homology Search during Recombination.” Nature Reviews Molecular Cell Biology, vol. 15, no. 6, Nature Publishing Group, 2014, pp. 369–83, doi:10.1038/nrm3805.","chicago":"Renkawitz, Jörg, Claudio Lademann, and Stefan Jentsch. “Mechanisms and Principles of Homology Search during Recombination.” Nature Reviews Molecular Cell Biology. Nature Publishing Group, 2014. https://doi.org/10.1038/nrm3805."},"language":[{"iso":"eng"}],"doi":"10.1038/nrm3805","date_published":"2014-05-14T00:00:00Z"},{"abstract":[{"text":"For innate and adaptive immune responses it is essential that inflammatory cells use quick and flexible locomotion strategies. Accordingly, most leukocytes can efficiently infiltrate and traverse almost every physiological or artificial environment. Here, we review how leukocytes might achieve this task mechanistically, and summarize recent findings on the principles of cytoskeletal force generation and transduction at the leading edge of leukocytes. We propose a model in which the cells switch between adhesion-receptor-mediated force transmission and locomotion modes that are based on cellular deformations, but independent of adhesion receptors. This plasticity in migration strategies allows leukocytes to adapt to the geometry and molecular composition of their environment.","lang":"eng"}],"publist_id":"2166","issue":"10","extern":1,"type":"journal_article","author":[{"full_name":"Jörg Renkawitz","last_name":"Renkawitz","first_name":"Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Michael Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt"}],"date_created":"2018-12-11T12:06:08Z","date_updated":"2021-01-12T07:53:30Z","volume":11,"_id":"3961","acknowledgement":"We are grateful to Michele Weber for critical comments on the manuscript. Work in the laboratory of M.S. is supported by the German Research Foundation, the Peter Hans Hofschneider Foundation for Experimental Biomedicine and the Max Planck Society. J.R. is supported by a PhD fellowship of the Böhringer Ingelheim Fond. We thank Reinhard Fässler and Stefan Jentsch for their continuous support.","year":"2010","title":"Mechanisms of force generation and force transmission during interstitial leukocyte migration","status":"public","publication_status":"published","publisher":"Wiley-Blackwell","intvolume":" 11","day":"24","month":"09","doi":"10.1038/embor.2010.147","date_published":"2010-09-24T00:00:00Z","publication":"EMBO Reports","citation":{"ista":"Renkawitz J, Sixt MK. 2010. Mechanisms of force generation and force transmission during interstitial leukocyte migration. EMBO Reports. 11(10), 744–750.","apa":"Renkawitz, J., & Sixt, M. K. (2010). Mechanisms of force generation and force transmission during interstitial leukocyte migration. EMBO Reports. Wiley-Blackwell. https://doi.org/10.1038/embor.2010.147","ieee":"J. Renkawitz and M. K. Sixt, “Mechanisms of force generation and force transmission during interstitial leukocyte migration,” EMBO Reports, vol. 11, no. 10. Wiley-Blackwell, pp. 744–750, 2010.","ama":"Renkawitz J, Sixt MK. Mechanisms of force generation and force transmission during interstitial leukocyte migration. EMBO Reports. 2010;11(10):744-750. doi:10.1038/embor.2010.147","chicago":"Renkawitz, Jörg, and Michael K Sixt. “Mechanisms of Force Generation and Force Transmission during Interstitial Leukocyte Migration.” EMBO Reports. Wiley-Blackwell, 2010. https://doi.org/10.1038/embor.2010.147.","mla":"Renkawitz, Jörg, and Michael K. Sixt. “Mechanisms of Force Generation and Force Transmission during Interstitial Leukocyte Migration.” EMBO Reports, vol. 11, no. 10, Wiley-Blackwell, 2010, pp. 744–50, doi:10.1038/embor.2010.147.","short":"J. Renkawitz, M.K. Sixt, EMBO Reports 11 (2010) 744–750."},"quality_controlled":0,"page":"744 - 750"},{"citation":{"ama":"Lämmermann T, Renkawitz J, Wu X, Hirsch K, Brakebusch C, Sixt MK. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper). Blood. 2009;113(23):5703-5710. doi:10.1182/blood-2008-11-191882","ieee":"T. Lämmermann, J. Renkawitz, X. Wu, K. Hirsch, C. Brakebusch, and M. K. Sixt, “Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper),” Blood, vol. 113, no. 23. American Society of Hematology, pp. 5703–5710, 2009.","apa":"Lämmermann, T., Renkawitz, J., Wu, X., Hirsch, K., Brakebusch, C., & Sixt, M. K. (2009). Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper). Blood. American Society of Hematology. https://doi.org/10.1182/blood-2008-11-191882","ista":"Lämmermann T, Renkawitz J, Wu X, Hirsch K, Brakebusch C, Sixt MK. 2009. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper). Blood. 113(23), 5703–5710.","short":"T. Lämmermann, J. Renkawitz, X. Wu, K. Hirsch, C. Brakebusch, M.K. Sixt, Blood 113 (2009) 5703–5710.","mla":"Lämmermann, Tim, et al. “Cdc42-Dependent Leading Edge Coordination Is Essential for Interstitial Dendritic Cell Migration (Plenary Paper).” Blood, vol. 113, no. 23, American Society of Hematology, 2009, pp. 5703–10, doi:10.1182/blood-2008-11-191882.","chicago":"Lämmermann, Tim, Jörg Renkawitz, Xunwei Wu, Karin Hirsch, Cord Brakebusch, and Michael K Sixt. “Cdc42-Dependent Leading Edge Coordination Is Essential for Interstitial Dendritic Cell Migration (Plenary Paper).” Blood. American Society of Hematology, 2009. https://doi.org/10.1182/blood-2008-11-191882."},"publication":"Blood","page":"5703 - 5710","quality_controlled":0,"doi":"10.1182/blood-2008-11-191882","date_published":"2009-06-04T00:00:00Z","day":"04","month":"06","_id":"3947","year":"2009","acknowledgement":"We thank Sylvia Cremer for help with statistics and critical reading of the paper and Reinhard Fässler for continuous support.\n\nThis work was supported by the German Research Foundation (Bonn, Germany), the Peter Hans Hofschneider Foundation for Experimental Biomedicine (Zürich, Switzerland), and the Max Planck Society (Munich, Germany).","publisher":"American Society of Hematology","intvolume":" 113","status":"public","publication_status":"published","title":"Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper)","author":[{"full_name":"Lämmermann, Tim","first_name":"Tim","last_name":"Lämmermann"},{"orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","first_name":"Jörg","full_name":"Jörg Renkawitz"},{"full_name":"Wu, Xunwei","first_name":"Xunwei","last_name":"Wu"},{"full_name":"Hirsch, Karin","last_name":"Hirsch","first_name":"Karin"},{"first_name":"Cord","last_name":"Brakebusch","full_name":"Brakebusch, Cord"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Michael Sixt"}],"volume":113,"date_created":"2018-12-11T12:06:03Z","date_updated":"2021-01-12T07:53:23Z","type":"journal_article","publist_id":"2179","issue":"23","abstract":[{"lang":"eng","text":"Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular proteolysis. Instead, the protrusive flow of the actin cytoskeleton directly drives a basal mode of locomotion that is occasionally supported by actomyosin contractions at the trailing edge to propel the cell's rigid nucleus. We here delete the small GTPase Cdc42 in DCs and find that actin flow and actomyosin contraction are still initiated in response to chemotactic cues. Accordingly, the cells are able to polarize and form protrusions. However, in the absence of Cdc42 the protrusions are temporally and spatially dysregulated, which leads to impaired leading edge coordination. Although this defect still allows the cells to move on 2-dimensional surfaces, their in vivo motility is completely abrogated. We show that this difference is entirely caused by the geometric complexity of the environment, as multiple competing protrusions lead to instantaneous entanglement within 3-dimensional extracellular matrix scaffolds. This demonstrates that the decisive factor for migrating DCs is not specific interaction with the extracellular environment, but adequate coordination of cytoskeletal flow."}],"extern":1},{"author":[{"orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","first_name":"Jörg","full_name":"Renkawitz, Jörg"},{"full_name":"Schumann, Kathrin","id":"F44D762E-4F9D-11E9-B64C-9EB26CEFFB5F","first_name":"Kathrin","last_name":"Schumann"},{"id":"3A3FC708-F248-11E8-B48F-1D18A9856A87","first_name":"Michele","last_name":"Weber","full_name":"Weber, Michele"},{"full_name":"Lämmermann, Tim","first_name":"Tim","last_name":"Lämmermann"},{"full_name":"Pflicke, Holger","last_name":"Pflicke","first_name":"Holger"},{"first_name":"Matthieu","last_name":"Piel","full_name":"Piel, Matthieu"},{"full_name":"Polleux, Julien","last_name":"Polleux","first_name":"Julien"},{"full_name":"Spatz, Joachim","first_name":"Joachim","last_name":"Spatz"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"volume":11,"oa_version":"None","date_updated":"2021-01-12T07:53:27Z","date_created":"2018-12-11T12:06:05Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"3954","acknowledgement":"We thank S. Cremer for statistical analysis, K. Hirsch for technical assistance, D. Critchley for talin1-deficient mice and R. Fässler for integrindeficient mice, discussions and critical reading of the manuscript. This work was supported by the German Research Foundation, the Peter Hans Hofschneider Foundation for Experimental Biomedicine, the Max Planck Society, the Alexander von Humboldt Foundation and the allergology programme of the Landesstiftung Baden-Württemberg.","year":"2009","intvolume":" 11","publisher":"Nature Publishing Group","status":"public","publication_status":"published","title":"Adaptive force transmission in amoeboid cell migration","publist_id":"2173","issue":"12","abstract":[{"text":"The leading front of a cell can either protrude as an actin-free membrane bleb that is inflated by actomyosin-driven contractile forces, or as an actin-rich pseudopodium, a site where polymerizing actin filaments push out the membrane. Pushing filaments can only cause the membrane to protrude if the expanding actin network experiences a retrograde counter-force, which is usually provided by transmembrane receptors of the integrin family. Here we show that chemotactic dendritic cells mechanically adapt to the adhesive properties of their substrate by switching between integrin-mediated and integrin-independent locomotion. We found that on engaging the integrin-actin clutch, actin polymerization was entirely turned into protrusion, whereas on disengagement actin underwent slippage and retrograde flow. Remarkably, accelerated retrograde flow was balanced by an increased actin polymerization rate; therefore, cell shape and protrusion velocity remained constant on alternating substrates. Due to this adaptive response in polymerization dynamics, tracks of adhesive substrate did not dictate the path of the cells. Instead, directional guidance was exclusively provided by a soluble gradient of chemoattractant, which endowed these 'amoeboid' cells with extraordinary flexibility, enabling them to traverse almost every type of tissue.","lang":"eng"}],"extern":"1","type":"journal_article","date_published":"2009-11-15T00:00:00Z","doi":"10.1038/ncb1992","language":[{"iso":"eng"}],"citation":{"mla":"Renkawitz, Jörg, et al. “Adaptive Force Transmission in Amoeboid Cell Migration.” Nature Cell Biology, vol. 11, no. 12, Nature Publishing Group, 2009, pp. 1438–43, doi:10.1038/ncb1992.","short":"J. Renkawitz, K. Schumann, M. Weber, T. Lämmermann, H. Pflicke, M. Piel, J. Polleux, J. Spatz, M.K. Sixt, Nature Cell Biology 11 (2009) 1438–1443.","chicago":"Renkawitz, Jörg, Kathrin Schumann, Michele Weber, Tim Lämmermann, Holger Pflicke, Matthieu Piel, Julien Polleux, Joachim Spatz, and Michael K Sixt. “Adaptive Force Transmission in Amoeboid Cell Migration.” Nature Cell Biology. Nature Publishing Group, 2009. https://doi.org/10.1038/ncb1992.","ama":"Renkawitz J, Schumann K, Weber M, et al. Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. 2009;11(12):1438-1443. doi:10.1038/ncb1992","ista":"Renkawitz J, Schumann K, Weber M, Lämmermann T, Pflicke H, Piel M, Polleux J, Spatz J, Sixt MK. 2009. Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. 11(12), 1438–1443.","apa":"Renkawitz, J., Schumann, K., Weber, M., Lämmermann, T., Pflicke, H., Piel, M., … Sixt, M. K. (2009). Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. Nature Publishing Group. https://doi.org/10.1038/ncb1992","ieee":"J. Renkawitz et al., “Adaptive force transmission in amoeboid cell migration,” Nature Cell Biology, vol. 11, no. 12. Nature Publishing Group, pp. 1438–1443, 2009."},"publication":"Nature Cell Biology","page":"1438 - 1443","day":"15","month":"11"}]