{"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"}],"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/"}],"department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"publication_status":"published","date_published":"2019-04-25T00:00:00Z","date_updated":"2024-03-25T23:30:22Z","pmid":1,"article_processing_charge":"No","month":"04","day":"25","type":"journal_article","status":"public","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":[{"status":"public","id":"14697","relation":"dissertation_contains"},{"status":"public","id":"6891","relation":"dissertation_contains"}]},"title":"Nuclear positioning facilitates amoeboid migration along the path of least resistance","quality_controlled":"1","scopus_import":"1","publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_created":"2019-04-17T06:52:28Z","oa_version":"Submitted Version","oa":1,"_id":"6328","language":[{"iso":"eng"}],"citation":{"mla":"Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” <i>Nature</i>, vol. 568, Springer Nature, 2019, pp. 546–50, doi:<a href=\"https://doi.org/10.1038/s41586-019-1087-5\">10.1038/s41586-019-1087-5</a>.","ieee":"J. Renkawitz <i>et al.</i>, “Nuclear positioning facilitates amoeboid migration along the path of least resistance,” <i>Nature</i>, 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. <i>Nature</i>. 2019;568:546-550. doi:<a href=\"https://doi.org/10.1038/s41586-019-1087-5\">10.1038/s41586-019-1087-5</a>","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.","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.” <i>Nature</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41586-019-1087-5\">https://doi.org/10.1038/s41586-019-1087-5</a>.","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. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-019-1087-5\">https://doi.org/10.1038/s41586-019-1087-5</a>","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."},"article_type":"letter_note","ec_funded":1,"external_id":{"pmid":["30944468"],"isi":["000465594200050"]},"author":[{"orcid":"0000-0003-2856-3369","full_name":"Renkawitz, Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","first_name":"Jörg","last_name":"Renkawitz"},{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","full_name":"Kopf, Aglaja","last_name":"Kopf","first_name":"Aglaja","orcid":"0000-0002-2187-6656"},{"first_name":"Julian A","last_name":"Stopp","full_name":"Stopp, Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87"},{"last_name":"de Vries","first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"de Vries, Ingrid"},{"last_name":"Driscoll","first_name":"Meghan K.","full_name":"Driscoll, Meghan K."},{"last_name":"Merrin","first_name":"Jack","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"last_name":"Hauschild","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522"},{"full_name":"Welf, Erik S.","first_name":"Erik S.","last_name":"Welf"},{"first_name":"Gaudenz","last_name":"Danuser","full_name":"Danuser, Gaudenz"},{"last_name":"Fiolka","first_name":"Reto","full_name":"Fiolka, Reto"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"publication":"Nature","doi":"10.1038/s41586-019-1087-5","page":"546-550","project":[{"grant_number":"281556","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","call_identifier":"FP7"},{"grant_number":"724373","name":"Cellular navigation along spatial gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","grant_number":"W01250-B20","_id":"265FAEBA-B435-11E9-9278-68D0E5697425","name":"Nano-Analytics of Cellular Systems"},{"call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","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"}],"isi":1,"acknowledged_ssus":[{"_id":"SSU"}],"year":"2019","volume":568,"intvolume":"       568"}