[{"oa_version":"Submitted Version","language":[{"iso":"eng"}],"date_updated":"2026-06-05T22:32:58Z","publication_status":"published","scopus_import":"1","external_id":{"isi":["000465594200050"],"pmid":["30944468"]},"acknowledged_ssus":[{"_id":"SSU"}],"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"}],"title":"Nuclear positioning facilitates amoeboid migration along the path of least resistance","doi":"10.1038/s41586-019-1087-5","publication":"Nature","page":"546-550","date_created":"2019-04-17T06:52:28Z","isi":1,"month":"04","intvolume":"       568","oa":1,"day":"25","year":"2019","date_published":"2019-04-25T00:00:00Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"MiSi"},{"_id":"NanoFab"},{"_id":"Bio"}],"author":[{"full_name":"Renkawitz, Jörg","last_name":"Renkawitz","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","first_name":"Jörg","orcid":"0000-0003-2856-3369"},{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","first_name":"Aglaja","orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja","last_name":"Kopf"},{"last_name":"Stopp","full_name":"Stopp, Julian A","first_name":"Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"de Vries, Ingrid","last_name":"de Vries"},{"first_name":"Meghan K.","full_name":"Driscoll, Meghan K.","last_name":"Driscoll"},{"last_name":"Merrin","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert"},{"first_name":"Erik S.","last_name":"Welf","full_name":"Welf, Erik S."},{"last_name":"Danuser","full_name":"Danuser, Gaudenz","first_name":"Gaudenz"},{"full_name":"Fiolka, Reto","last_name":"Fiolka","first_name":"Reto"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"}],"_id":"6328","article_processing_charge":"No","publisher":"Springer Nature","volume":568,"ec_funded":1,"status":"public","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"14697"},{"relation":"dissertation_contains","status":"public","id":"6891"}],"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/","relation":"press_release"}]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/"}],"article_type":"letter_note","citation":{"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.","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.","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.","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>.","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>."},"pmid":1,"type":"journal_article","project":[{"_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","call_identifier":"FP7","grant_number":"281556"},{"grant_number":"724373","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular Navigation Along Spatial Gradients"},{"grant_number":"W01250-B20","_id":"265FAEBA-B435-11E9-9278-68D0E5697425","name":"Nano-Analytics of Cellular Systems","call_identifier":"FWF"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"name":"Molecular and system level view of immune cell migration","_id":"25A48D24-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1396-2014"}],"quality_controlled":"1"},{"doi":"10.1016/j.cell.2019.08.047","title":"The neural crest pitches in to remove apoptotic debris","external_id":{"isi":["000486618500011"],"pmid":["31539498"]},"scopus_import":"1","publication_status":"published","date_updated":"2026-06-05T22:32:57Z","oa_version":"None","language":[{"iso":"eng"}],"intvolume":"       179","isi":1,"month":"09","page":"51-53","publication":"Cell","date_created":"2019-09-15T22:00:46Z","status":"public","volume":179,"publisher":"Elsevier","author":[{"full_name":"Kopf, Aglaja","last_name":"Kopf","first_name":"Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K"}],"_id":"6877","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"}],"year":"2019","day":"19","date_published":"2019-09-19T00:00:00Z","type":"journal_article","quality_controlled":"1","pmid":1,"citation":{"mla":"Kopf, Aglaja, and Michael K. Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” <i>Cell</i>, vol. 179, no. 1, Elsevier, 2019, pp. 51–53, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">10.1016/j.cell.2019.08.047</a>.","ama":"Kopf A, Sixt MK. The neural crest pitches in to remove apoptotic debris. <i>Cell</i>. 2019;179(1):51-53. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">10.1016/j.cell.2019.08.047</a>","ista":"Kopf A, Sixt MK. 2019. The neural crest pitches in to remove apoptotic debris. Cell. 179(1), 51–53.","chicago":"Kopf, Aglaja, and Michael K Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” <i>Cell</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">https://doi.org/10.1016/j.cell.2019.08.047</a>.","short":"A. Kopf, M.K. Sixt, Cell 179 (2019) 51–53.","ieee":"A. Kopf and M. K. Sixt, “The neural crest pitches in to remove apoptotic debris,” <i>Cell</i>, vol. 179, no. 1. Elsevier, pp. 51–53, 2019.","apa":"Kopf, A., &#38; Sixt, M. K. (2019). The neural crest pitches in to remove apoptotic debris. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">https://doi.org/10.1016/j.cell.2019.08.047</a>"},"article_type":"original","issue":"1","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6891"}]},"publication_identifier":{"eissn":["1097-4172"],"issn":["0092-8674"]}},{"department":[{"_id":"MiSi"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","year":"2019","day":"09","date_published":"2019-10-09T00:00:00Z","publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"article_processing_charge":"No","_id":"6947","author":[{"last_name":"Assen","full_name":"Assen, Frank P","orcid":"0000-0003-3470-6119","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","first_name":"Frank P"}],"file":[{"access_level":"closed","date_updated":"2020-11-07T23:30:03Z","date_created":"2019-11-06T12:30:02Z","file_size":214172667,"checksum":"53a739752a500f84d0f8ec953cbbd0b6","file_name":"PhDthesis_FrankAssen_revised2.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"fassen","file_id":"6990","embargo_to":"open_access","relation":"source_file"},{"relation":"main_file","embargo":"2020-11-06","file_id":"6991","creator":"fassen","content_type":"application/pdf","file_name":"PhDthesis_FrankAssen_revised2.pdf","checksum":"8c156b65d9347bb599623a4b09f15d15","date_created":"2019-11-06T12:30:57Z","file_size":83637532,"date_updated":"2020-11-07T23:30:03Z","access_level":"open_access"}],"status":"public","file_date_updated":"2020-11-07T23:30:03Z","publication_identifier":{"issn":["2663-337X"]},"has_accepted_license":"1","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"402"},{"id":"664","status":"public","relation":"part_of_dissertation"}]},"citation":{"ieee":"F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking,” Institute of Science and Technology Austria, 2019.","apa":"Assen, F. P. (2019). <i>Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>","chicago":"Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6947\">https://doi.org/10.15479/AT:ISTA:6947</a>.","short":"F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and Technology Austria, 2019.","ista":"Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria.","ama":"Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>","mla":"Assen, Frank P. <i>Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6947\">10.15479/AT:ISTA:6947</a>."},"type":"dissertation","oa_version":"Published Version","language":[{"iso":"eng"}],"date_updated":"2026-04-08T14:01:50Z","publication_status":"published","degree_awarded":"PhD","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"abstract":[{"text":"Lymph nodes  are es s ential organs  of the immune  s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular  cells (FRCs) are  the  main  stromal  cells and  form  a sponge-like extracellular matrix network,   called  conduits ,  which  they   thems elves   enwrap   and  contract.  Lymph,  containing  s oluble  antigens ,  arrive in  lymph  nodes  via afferent lymphatic  vessels that  connect  to  the  s ubcaps ular  s inus   and  conduit  network.  According  to  the  current  paradigm,  the  conduit  network   dis tributes   afferent  lymph  through   lymph  nodes   and  thus   provides   acces s   for  immune  cells to lymph-borne  antigens. An  elas tic  caps ule  s urrounds   the  organ  and  confines   the immune  cells and  FRC  network.   Lymph   nodes   are  completely  packed  with  lymphocytes   and  lymphocyte  numbers  directly  dictates  the size  of  the  organ.  Although  lymphocytes   cons tantly  enter  and  leave  the  lymph  node,  its   s ize  remains   remarkedly   s table  under  homeostatic conditions. It is only partly known  how the cellularity and s ize of the lymph node is regulated and  how  the  lymph  node  is able to swell in inflammation.  The role of the FRC network   in  lymph  node   s welling  and  trans fer  of  fluids   are  inves tigated in  this   thes is.  Furthermore,   we  s tudied  what  trafficking  routes   are  us ed  by  cancer  cells   in  lymph  nodes   to  form  distal metastases.We examined the role of a mechanical feedback in regulation of lymph  node swelling. Using parallel plate compression  and UV-las er  cutting  experiments   we  dis s ected  the  mechanical  force dynamics  of the whole lymph  node, and individually for FRCs  and the  caps ule. Physical forces   generated  by  packed  lymphocytes   directly  affect  the  tens ion  on  the  FRC  network  and  capsule,  which  increases  its  resistance  to   swelling.  This  implies  a  feedback  mechanism  between   tis s ue   pres s ure   and   ability   of   lymphocytes    to   enter   the   organ.   Following   inflammation,  the  lymph  node  swells ∼10 fold in two weeks . Yet, what  is  the role  for tens ion on  the  FRC  network   and  caps ule,  and  how  are  lymphocytes   able  to  enter  in  conditions  that resist swelling remain open ques tions . We s how that tens ion on the FRC network is  important to  limit  the  swelling  rate  of  the  organ  so  that  the  FRC  network  can  grow  in  a  coordinated  fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates  and a dis organized FRC network  in the inflamed lymph  node. Growth  of the FRC network  in  turn  is   expected  to  releas e  tens ion  on  thes e  s tructures   and  lowers   the  res is tance  to  swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of  swelling coincides   with  a  thickening  of  the  caps ule,  which  forms   a  thick  res is tant  band  around  the organ and lowers  tens ion on the FRC network  to form a new force equilibrium.The  FRC  and  conduit   network   are  further   believed  to  be  a  privileged  s ite  of  s oluble  information  within  the  lymph  node,  although  many  details   remain  uns olved.  We  s how  by  3D  ultra-recons truction   that  FRCs   and  antigen  pres enting  cells   cover  the  s urface  of  conduit  s ys tem for more  than 99% and we dis cus s  the implications  for s oluble information  exchangeat the conduit level.Finally, there  is an ongoing debate in the cancer field whether and how cancer cells  in lymph nodes   s eed  dis tal  metas tas es .  We  s how  that  cancer  cells   infus ed  into  the  lymph  node  can  utilize trafficking routes of immune  cells and  rapidly  migrate  to  blood  vessels. Once  in  the  blood circulation,  these cells are able to form  metastases in distal tissues.","lang":"eng"}],"title":"Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking","doi":"10.15479/AT:ISTA:6947","OA_place":"publisher","page":"142","date_created":"2019-10-14T16:54:52Z","ddc":["570"],"month":"10","supervisor":[{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"corr_author":"1","oa":1},{"has_accepted_license":"1","issue":"6","citation":{"short":"M. Brown, L. Johnson, D. Leone, P. Májek, K. Vaahtomeri, D. Senfter, N. Bukosza, H. Schachner, G. Asfour, B. Langer, R. Hauschild, K. Parapatics, Y. Hong, K. Bennett, R. Kain, M. Detmar, M.K. Sixt, D. Jackson, D. Kerjaschki, Journal of Cell Biology 217 (2018) 2205–2221.","chicago":"Brown, Markus, Louise Johnson, Dario Leone, Peter Májek, Kari Vaahtomeri, Daniel Senfter, Nora Bukosza, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>.","ieee":"M. Brown <i>et al.</i>, “Lymphatic exosomes promote dendritic cell migration along guidance cues,” <i>Journal of Cell Biology</i>, vol. 217, no. 6. Rockefeller University Press, pp. 2205–2221, 2018.","apa":"Brown, M., Johnson, L., Leone, D., Májek, P., Vaahtomeri, K., Senfter, D., … Kerjaschki, D. (2018). Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.201612051\">https://doi.org/10.1083/jcb.201612051</a>","ista":"Brown M, Johnson L, Leone D, Májek P, Vaahtomeri K, Senfter D, Bukosza N, Schachner H, Asfour G, Langer B, Hauschild R, Parapatics K, Hong Y, Bennett K, Kain R, Detmar M, Sixt MK, Jackson D, Kerjaschki D. 2018. Lymphatic exosomes promote dendritic cell migration along guidance cues. Journal of Cell Biology. 217(6), 2205–2221.","ama":"Brown M, Johnson L, Leone D, et al. Lymphatic exosomes promote dendritic cell migration along guidance cues. <i>Journal of Cell Biology</i>. 2018;217(6):2205-2221. doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>","mla":"Brown, Markus, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration along Guidance Cues.” <i>Journal of Cell Biology</i>, vol. 217, no. 6, Rockefeller University Press, 2018, pp. 2205–21, doi:<a href=\"https://doi.org/10.1083/jcb.201612051\">10.1083/jcb.201612051</a>."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","project":[{"grant_number":"Y 564-B12","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"},{"grant_number":"281556","call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A603A2-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","pmid":1,"department":[{"_id":"MiSi"},{"_id":"Bio"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","day":"12","year":"2018","date_published":"2018-04-12T00:00:00Z","publisher":"Rockefeller University Press","article_processing_charge":"No","_id":"275","author":[{"last_name":"Brown","full_name":"Brown, Markus","first_name":"Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Louise","full_name":"Johnson, Louise","last_name":"Johnson"},{"first_name":"Dario","last_name":"Leone","full_name":"Leone, Dario"},{"full_name":"Májek, Peter","last_name":"Májek","first_name":"Peter"},{"orcid":"0000-0001-7829-3518","first_name":"Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri","full_name":"Vaahtomeri, Kari"},{"first_name":"Daniel","last_name":"Senfter","full_name":"Senfter, Daniel"},{"last_name":"Bukosza","full_name":"Bukosza, Nora","first_name":"Nora"},{"first_name":"Helga","last_name":"Schachner","full_name":"Schachner, Helga"},{"full_name":"Asfour, Gabriele","last_name":"Asfour","first_name":"Gabriele"},{"first_name":"Brigitte","full_name":"Langer, Brigitte","last_name":"Langer"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522"},{"last_name":"Parapatics","full_name":"Parapatics, Katja","first_name":"Katja"},{"first_name":"Young","full_name":"Hong, Young","last_name":"Hong"},{"first_name":"Keiryn","full_name":"Bennett, Keiryn","last_name":"Bennett"},{"last_name":"Kain","full_name":"Kain, Renate","first_name":"Renate"},{"first_name":"Michael","full_name":"Detmar, Michael","last_name":"Detmar"},{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"},{"full_name":"Jackson, David","last_name":"Jackson","first_name":"David"},{"full_name":"Kerjaschki, Dontscho","last_name":"Kerjaschki","first_name":"Dontscho"}],"license":"https://creativecommons.org/licenses/by/4.0/","file":[{"date_updated":"2020-07-14T12:45:45Z","access_level":"open_access","file_size":2252043,"date_created":"2018-12-17T12:50:07Z","creator":"dernst","content_type":"application/pdf","file_name":"2018_JournalCellBiology_Brown.pdf","checksum":"9c7eba51a35c62da8c13f98120b64df4","relation":"main_file","file_id":"5704"}],"status":"public","ec_funded":1,"file_date_updated":"2020-07-14T12:45:45Z","volume":217,"acknowledgement":"M. Brown was supported by the Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund and Medizinische Universität Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung and Advanced European Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland postdoctoral research grant (287853). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668036 (RELENT).","publist_id":"7627","page":"2205 - 2221","publication":"Journal of Cell Biology","date_created":"2018-12-11T11:45:33Z","isi":1,"ddc":["570"],"month":"04","corr_author":"1","intvolume":"       217","oa":1,"oa_version":"Published Version","language":[{"iso":"eng"}],"scopus_import":"1","date_updated":"2025-04-14T13:10:20Z","publication_status":"published","abstract":[{"lang":"eng","text":"Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified &gt; 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments."}],"title":"Lymphatic exosomes promote dendritic cell migration along guidance cues","external_id":{"pmid":["29650776"],"isi":["000438077800026"]},"doi":"10.1083/jcb.201612051"},{"_id":"276","article_processing_charge":"No","author":[{"first_name":"Corina","last_name":"Frick","full_name":"Frick, Corina"},{"full_name":"Dettinger, Philip","last_name":"Dettinger","first_name":"Philip"},{"orcid":"0000-0003-2856-3369","first_name":"Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","last_name":"Renkawitz","full_name":"Renkawitz, Jörg"},{"first_name":"Annaïse","full_name":"Jauch, Annaïse","last_name":"Jauch"},{"last_name":"Berger","full_name":"Berger, Christoph","first_name":"Christoph"},{"last_name":"Recher","full_name":"Recher, Mike","first_name":"Mike"},{"first_name":"Timm","last_name":"Schroeder","full_name":"Schroeder, Timm"},{"first_name":"Matthias","full_name":"Mehling, Matthias","last_name":"Mehling"}],"publisher":"Public Library of Science","date_published":"2018-06-07T00:00:00Z","year":"2018","day":"07","department":[{"_id":"MiSi"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publist_id":"7626","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.","volume":13,"file_date_updated":"2020-07-14T12:45:45Z","status":"public","file":[{"creator":"dernst","file_name":"2018_Plos_Frick.pdf","content_type":"application/pdf","checksum":"95fc5dc3938b3ad3b7697d10c83cc143","relation":"main_file","file_id":"5709","date_updated":"2020-07-14T12:45:45Z","access_level":"open_access","date_created":"2018-12-17T14:10:32Z","file_size":7682167}],"article_number":"e0198330","issue":"6","has_accepted_license":"1","quality_controlled":"1","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","citation":{"mla":"Frick, Corina, et al. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” <i>PLoS One</i>, vol. 13, no. 6, e0198330, Public Library of Science, 2018, doi:<a href=\"https://doi.org/10.1371/journal.pone.0198330\">10.1371/journal.pone.0198330</a>.","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. <i>PLoS One</i>. 2018;13(6). doi:<a href=\"https://doi.org/10.1371/journal.pone.0198330\">10.1371/journal.pone.0198330</a>","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.” <i>PLoS One</i>. Public Library of Science, 2018. <a href=\"https://doi.org/10.1371/journal.pone.0198330\">https://doi.org/10.1371/journal.pone.0198330</a>.","short":"C. Frick, P. Dettinger, J. Renkawitz, A. Jauch, C. Berger, M. Recher, T. Schroeder, M. Mehling, PLoS One 13 (2018).","ieee":"C. Frick <i>et al.</i>, “Nano-scale microfluidics to study 3D chemotaxis at the single cell level,” <i>PLoS One</i>, 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. <i>PLoS One</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0198330\">https://doi.org/10.1371/journal.pone.0198330</a>"},"date_updated":"2023-09-13T09:00:15Z","publication_status":"published","scopus_import":"1","language":[{"iso":"eng"}],"oa_version":"Published Version","doi":"10.1371/journal.pone.0198330","external_id":{"isi":["000434384900031"]},"title":"Nano-scale microfluidics to study 3D chemotaxis at the single cell level","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."}],"month":"06","isi":1,"ddc":["570"],"date_created":"2018-12-11T11:45:34Z","publication":"PLoS One","oa":1,"intvolume":"        13"},{"date_created":"2018-12-11T11:45:44Z","publication":"Developmental Cell","page":"331 - 346","corr_author":"1","month":"05","isi":1,"intvolume":"        45","oa":1,"language":[{"iso":"eng"}],"oa_version":"Published Version","publication_status":"published","date_updated":"2024-10-22T10:12:36Z","scopus_import":"1","external_id":{"pmid":["29738712"],"isi":["000432461400009"]},"abstract":[{"text":"Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo.","lang":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"title":"Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration","doi":"10.1016/j.devcel.2018.04.002","related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/cells-change-tension-to-make-tissue-barriers-easier-to-get-through/","description":"News on IST Homepage"}]},"issue":"3","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.devcel.2018.04.002"}],"article_type":"original","citation":{"mla":"Ratheesh, Aparna, et al. “Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.” <i>Developmental Cell</i>, vol. 45, no. 3, Elsevier, 2018, pp. 331–46, doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">10.1016/j.devcel.2018.04.002</a>.","ama":"Ratheesh A, Bicher J, Smutny M, et al. Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration. <i>Developmental Cell</i>. 2018;45(3):331-346. doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">10.1016/j.devcel.2018.04.002</a>","ista":"Ratheesh A, Bicher J, Smutny M, Veselá J, Papusheva E, Krens G, Kaufmann W, György A, Casano AM, Siekhaus DE. 2018. Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration. Developmental Cell. 45(3), 331–346.","short":"A. Ratheesh, J. Bicher, M. Smutny, J. Veselá, E. Papusheva, G. Krens, W. Kaufmann, A. György, A.M. Casano, D.E. Siekhaus, Developmental Cell 45 (2018) 331–346.","chicago":"Ratheesh, Aparna, Julia Bicher, Michael Smutny, Jana Veselá, Ekaterina Papusheva, Gabriel Krens, Walter Kaufmann, Attila György, Alessandra M Casano, and Daria E Siekhaus. “Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.” <i>Developmental Cell</i>. Elsevier, 2018. <a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">https://doi.org/10.1016/j.devcel.2018.04.002</a>.","apa":"Ratheesh, A., Bicher, J., Smutny, M., Veselá, J., Papusheva, E., Krens, G., … Siekhaus, D. E. (2018). Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2018.04.002\">https://doi.org/10.1016/j.devcel.2018.04.002</a>","ieee":"A. Ratheesh <i>et al.</i>, “Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration,” <i>Developmental Cell</i>, vol. 45, no. 3. Elsevier, pp. 331–346, 2018."},"pmid":1,"quality_controlled":"1","project":[{"grant_number":"P29638","call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425","name":"The role of Drosophila TNF alpha in immune cell invasion"},{"name":"Investigating the role of transporters in invasive migration through junctions","_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"334077"}],"type":"journal_article","date_published":"2018-05-07T00:00:00Z","day":"07","year":"2018","department":[{"_id":"DaSi"},{"_id":"CaHe"},{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"MiSi"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"308","author":[{"last_name":"Ratheesh","full_name":"Ratheesh, Aparna","orcid":"0000-0001-7190-0776","first_name":"Aparna","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Biebl, Julia","last_name":"Biebl","first_name":"Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Michael","full_name":"Smutny, Michael","last_name":"Smutny"},{"first_name":"Jana","id":"433253EE-F248-11E8-B48F-1D18A9856A87","full_name":"Veselá, Jana","last_name":"Veselá"},{"first_name":"Ekaterina","id":"41DB591E-F248-11E8-B48F-1D18A9856A87","full_name":"Papusheva, Ekaterina","last_name":"Papusheva"},{"orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","last_name":"Krens","full_name":"Krens, Gabriel"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter"},{"last_name":"György","full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","first_name":"Attila"},{"orcid":"0000-0002-6009-6804","id":"3DBA3F4E-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandra M","last_name":"Casano","full_name":"Casano, Alessandra M"},{"last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E"}],"article_processing_charge":"No","publisher":"Elsevier","volume":45,"status":"public","ec_funded":1},{"external_id":{"isi":["000426150700002"],"pmid":["29486189"]},"title":"A fat lot of good for wound healing","abstract":[{"lang":"eng","text":"The insect’s fat body combines metabolic and immunological functions. In this issue of Developmental Cell, Franz et al. (2018) show that in Drosophila, cells of the fat body are not static, but can actively “swim” toward sites of epithelial injury, where they physically clog the wound and locally secrete antimicrobial peptides."}],"doi":"10.1016/j.devcel.2018.02.009","language":[{"iso":"eng"}],"oa_version":"Published Version","date_updated":"2024-10-09T20:58:17Z","publication_status":"published","scopus_import":"1","intvolume":"        44","oa":1,"date_created":"2018-12-11T11:45:47Z","publication":"Developmental Cell","page":"405 - 406","corr_author":"1","month":"02","isi":1,"volume":44,"status":"public","publist_id":"7547","acknowledgement":"Short Survey","date_published":"2018-02-26T00:00:00Z","year":"2018","day":"26","department":[{"_id":"MiSi"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"318","author":[{"orcid":"0000-0002-6009-6804","first_name":"Alessandra M","id":"3DBA3F4E-F248-11E8-B48F-1D18A9856A87","last_name":"Casano","full_name":"Casano, Alessandra M"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"article_processing_charge":"No","publisher":"Cell Press","citation":{"mla":"Casano, Alessandra M., and Michael K. Sixt. “A Fat Lot of Good for Wound Healing.” <i>Developmental Cell</i>, vol. 44, no. 4, Cell Press, 2018, pp. 405–06, doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">10.1016/j.devcel.2018.02.009</a>.","chicago":"Casano, Alessandra M, and Michael K Sixt. “A Fat Lot of Good for Wound Healing.” <i>Developmental Cell</i>. Cell Press, 2018. <a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">https://doi.org/10.1016/j.devcel.2018.02.009</a>.","short":"A.M. Casano, M.K. Sixt, Developmental Cell 44 (2018) 405–406.","apa":"Casano, A. M., &#38; Sixt, M. K. (2018). A fat lot of good for wound healing. <i>Developmental Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">https://doi.org/10.1016/j.devcel.2018.02.009</a>","ieee":"A. M. Casano and M. K. Sixt, “A fat lot of good for wound healing,” <i>Developmental Cell</i>, vol. 44, no. 4. Cell Press, pp. 405–406, 2018.","ama":"Casano AM, Sixt MK. A fat lot of good for wound healing. <i>Developmental Cell</i>. 2018;44(4):405-406. doi:<a href=\"https://doi.org/10.1016/j.devcel.2018.02.009\">10.1016/j.devcel.2018.02.009</a>","ista":"Casano AM, Sixt MK. 2018. A fat lot of good for wound healing. Developmental Cell. 44(4), 405–406."},"pmid":1,"quality_controlled":"1","type":"journal_article","issue":"4","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/29486189"}]},{"publisher":"Academic Press","_id":"153","article_processing_charge":"No","author":[{"full_name":"Renkawitz, Jörg","last_name":"Renkawitz","first_name":"Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369"},{"full_name":"Reversat, Anne","last_name":"Reversat","first_name":"Anne","id":"35B76592-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0666-8928"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X"},{"full_name":"Merrin, Jack","last_name":"Merrin","first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"MiSi"},{"_id":"NanoFab"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2018-07-27T00:00:00Z","year":"2018","day":"27","publist_id":"7768","status":"public","volume":147,"publication_identifier":{"issn":["0091-679X"]},"quality_controlled":"1","type":"book_chapter","pmid":1,"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.","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: <i>Methods in Cell Biology</i>. Vol 147. Academic Press; 2018:79-91. doi:<a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">10.1016/bs.mcb.2018.07.004</a>","short":"J. Renkawitz, A. Reversat, A.F. Leithner, J. Merrin, M.K. Sixt, in:, Methods in Cell Biology, Academic Press, 2018, pp. 79–91.","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 <i>Methods in Cell Biology</i>, 147:79–91. Academic Press, 2018. <a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">https://doi.org/10.1016/bs.mcb.2018.07.004</a>.","apa":"Renkawitz, J., Reversat, A., Leithner, A. F., Merrin, J., &#38; Sixt, M. K. (2018). Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In <i>Methods in Cell Biology</i> (Vol. 147, pp. 79–91). Academic Press. <a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">https://doi.org/10.1016/bs.mcb.2018.07.004</a>","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 <i>Methods in Cell Biology</i>, vol. 147, Academic Press, 2018, pp. 79–91.","mla":"Renkawitz, Jörg, et al. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” <i>Methods in Cell Biology</i>, vol. 147, Academic Press, 2018, pp. 79–91, doi:<a href=\"https://doi.org/10.1016/bs.mcb.2018.07.004\">10.1016/bs.mcb.2018.07.004</a>."},"scopus_import":"1","date_updated":"2025-07-10T11:51:09Z","publication_status":"published","language":[{"iso":"eng"}],"oa_version":"None","doi":"10.1016/bs.mcb.2018.07.004","title":"Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments","abstract":[{"lang":"eng","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."}],"external_id":{"isi":["000452412300006"],"pmid":["30165964"]},"month":"07","isi":1,"date_created":"2018-12-11T11:44:54Z","page":"79 - 91","publication":"Methods in Cell Biology","intvolume":"       147"},{"oa_version":"Published Version","language":[{"iso":"eng"}],"date_updated":"2025-07-10T11:53:04Z","publication_status":"published","scopus_import":"1","external_id":{"isi":["000456783800011"]},"title":"Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data","abstract":[{"text":"Spatial patterns are ubiquitous on the subcellular, cellular and tissue level, and can be studied using imaging techniques such as light and fluorescence microscopy. Imaging data provide quantitative information about biological systems; however, mechanisms causing spatial patterning often remain elusive. In recent years, spatio-temporal mathematical modelling has helped to overcome this problem. Yet, outliers and structured noise limit modelling of whole imaging data, and models often consider spatial summary statistics. Here, we introduce an integrated data-driven modelling approach that can cope with measurement artefacts and whole imaging data. Our approach combines mechanistic models of the biological processes with robust statistical models of the measurement process. The parameters of the integrated model are calibrated using a maximum-likelihood approach. We used this integrated modelling approach to study in vivo gradients of the chemokine (C-C motif) ligand 21 (CCL21). CCL21 gradients guide dendritic cells and are important in the adaptive immune response. Using artificial data, we verified that the integrated modelling approach provides reliable parameter estimates in the presence of measurement noise and that bias and variance of these estimates are reduced compared to conventional approaches. The application to experimental data allowed the parametrization and subsequent refinement of the model using additional mechanisms. Among other results, model-based hypothesis testing predicted lymphatic vessel-dependent concentration of heparan sulfate, the binding partner of CCL21. The selected model provided an accurate description of the experimental data and was partially validated using published data. Our findings demonstrate that integrated statistical modelling of whole imaging data is computationally feasible and can provide novel biological insights.","lang":"eng"}],"doi":"10.1098/rsif.2018.0600","publication":"Journal of the Royal Society Interface","date_created":"2019-01-20T22:59:18Z","isi":1,"ddc":["570"],"month":"12","intvolume":"        15","oa":1,"year":"2018","day":"05","date_published":"2018-12-05T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"}],"_id":"5858","author":[{"first_name":"Sabrina","last_name":"Hross","full_name":"Hross, Sabrina"},{"full_name":"Theis, Fabian J.","last_name":"Theis","first_name":"Fabian J."},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"},{"first_name":"Jan","last_name":"Hasenauer","full_name":"Hasenauer, Jan"}],"article_processing_charge":"No","publisher":"Royal Society Publishing","file_date_updated":"2020-07-14T12:47:13Z","volume":15,"file":[{"date_updated":"2020-07-14T12:47:13Z","access_level":"open_access","date_created":"2019-02-05T14:46:44Z","file_size":1464288,"creator":"dernst","file_name":"2018_Interface_Hross.pdf","checksum":"56eb4308a15b7190bff938fab1f780e8","content_type":"application/pdf","relation":"main_file","file_id":"5925"}],"status":"public","publication_identifier":{"issn":["1742-5689"]},"has_accepted_license":"1","issue":"149","article_number":"20180600","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"citation":{"mla":"Hross, Sabrina, et al. “Mechanistic Description of Spatial Processes Using Integrative Modelling of Noise-Corrupted Imaging Data.” <i>Journal of the Royal Society Interface</i>, vol. 15, no. 149, 20180600, Royal Society Publishing, 2018, doi:<a href=\"https://doi.org/10.1098/rsif.2018.0600\">10.1098/rsif.2018.0600</a>.","ama":"Hross S, Theis FJ, Sixt MK, Hasenauer J. Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data. <i>Journal of the Royal Society Interface</i>. 2018;15(149). doi:<a href=\"https://doi.org/10.1098/rsif.2018.0600\">10.1098/rsif.2018.0600</a>","ista":"Hross S, Theis FJ, Sixt MK, Hasenauer J. 2018. Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data. Journal of the Royal Society Interface. 15(149), 20180600.","ieee":"S. Hross, F. J. Theis, M. K. Sixt, and J. Hasenauer, “Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data,” <i>Journal of the Royal Society Interface</i>, vol. 15, no. 149. Royal Society Publishing, 2018.","apa":"Hross, S., Theis, F. J., Sixt, M. K., &#38; Hasenauer, J. (2018). Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data. <i>Journal of the Royal Society Interface</i>. Royal Society Publishing. <a href=\"https://doi.org/10.1098/rsif.2018.0600\">https://doi.org/10.1098/rsif.2018.0600</a>","short":"S. Hross, F.J. Theis, M.K. Sixt, J. Hasenauer, Journal of the Royal Society Interface 15 (2018).","chicago":"Hross, Sabrina, Fabian J. Theis, Michael K Sixt, and Jan Hasenauer. “Mechanistic Description of Spatial Processes Using Integrative Modelling of Noise-Corrupted Imaging Data.” <i>Journal of the Royal Society Interface</i>. Royal Society Publishing, 2018. <a href=\"https://doi.org/10.1098/rsif.2018.0600\">https://doi.org/10.1098/rsif.2018.0600</a>."},"type":"journal_article","quality_controlled":"1"},{"external_id":{"isi":["000434375000001"]},"title":"The cell sets the tone","abstract":[{"lang":"eng","text":"In zebrafish larvae, it is the cell type that determines how the cell responds to a chemokine signal."}],"doi":"10.7554/eLife.37888","oa_version":"Published Version","language":[{"iso":"eng"}],"publication_status":"published","date_updated":"2025-07-10T11:53:05Z","scopus_import":"1","intvolume":"         7","oa":1,"publication":"eLife","date_created":"2019-01-20T22:59:19Z","corr_author":"1","ddc":["570"],"isi":1,"month":"06","file_date_updated":"2020-07-14T12:47:13Z","volume":7,"file":[{"date_created":"2019-02-13T10:52:11Z","file_size":358141,"date_updated":"2020-07-14T12:47:13Z","access_level":"open_access","relation":"main_file","file_id":"5973","creator":"dernst","file_name":"2018_eLife_Alanko.pdf","content_type":"application/pdf","checksum":"f1c7ec2a809408d763c4b529a98f9a3b"}],"status":"public","day":"06","year":"2018","date_published":"2018-06-06T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"}],"_id":"5861","author":[{"first_name":"Jonna H","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7698-3061","full_name":"Alanko, Jonna H","last_name":"Alanko"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"}],"article_processing_charge":"No","publisher":"eLife Sciences Publications","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"citation":{"mla":"Alanko, Jonna H., and Michael K. Sixt. “The Cell Sets the Tone.” <i>ELife</i>, vol. 7, e37888, eLife Sciences Publications, 2018, doi:<a href=\"https://doi.org/10.7554/eLife.37888\">10.7554/eLife.37888</a>.","ama":"Alanko JH, Sixt MK. The cell sets the tone. <i>eLife</i>. 2018;7. doi:<a href=\"https://doi.org/10.7554/eLife.37888\">10.7554/eLife.37888</a>","ista":"Alanko JH, Sixt MK. 2018. The cell sets the tone. eLife. 7, e37888.","ieee":"J. H. Alanko and M. K. Sixt, “The cell sets the tone,” <i>eLife</i>, vol. 7. eLife Sciences Publications, 2018.","apa":"Alanko, J. H., &#38; Sixt, M. K. (2018). The cell sets the tone. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.37888\">https://doi.org/10.7554/eLife.37888</a>","chicago":"Alanko, Jonna H, and Michael K Sixt. “The Cell Sets the Tone.” <i>ELife</i>. eLife Sciences Publications, 2018. <a href=\"https://doi.org/10.7554/eLife.37888\">https://doi.org/10.7554/eLife.37888</a>.","short":"J.H. Alanko, M.K. Sixt, ELife 7 (2018)."},"type":"journal_article","quality_controlled":"1","publication_identifier":{"issn":["2050-084X"]},"has_accepted_license":"1","article_number":"e37888"},{"title":"Optical functionalization of human class A orphan G-protein-coupled receptors","abstract":[{"lang":"eng","text":"G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs."}],"external_id":{"isi":["000432280000006"]},"doi":"10.1038/s41467-018-04342-1","language":[{"iso":"eng"}],"oa_version":"Published Version","scopus_import":"1","publication_status":"published","date_updated":"2025-04-15T07:22:42Z","intvolume":"         9","oa":1,"date_created":"2019-02-14T10:50:24Z","publication":"Nature Communications","month":"12","ddc":["570"],"isi":1,"status":"public","ec_funded":1,"file":[{"file_size":1349914,"date_created":"2019-02-14T10:58:29Z","access_level":"open_access","date_updated":"2020-07-14T12:47:14Z","file_id":"5985","relation":"main_file","content_type":"application/pdf","checksum":"8325fcc194264af4749e662a73bf66b5","file_name":"2018_Springer_Morri.pdf","creator":"kschuh"}],"file_date_updated":"2020-07-14T12:47:14Z","volume":9,"department":[{"_id":"HaJa"},{"_id":"CaGu"},{"_id":"MiSi"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_published":"2018-12-01T00:00:00Z","year":"2018","day":"01","publisher":"Springer Nature","article_processing_charge":"No","_id":"5984","author":[{"first_name":"Maurizio","id":"4863116E-F248-11E8-B48F-1D18A9856A87","full_name":"Morri, Maurizio","last_name":"Morri"},{"full_name":"Sanchez-Romero, Inmaculada","last_name":"Sanchez-Romero","first_name":"Inmaculada","id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alexandra-Madelaine","id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87","last_name":"Tichy","full_name":"Tichy, Alexandra-Madelaine"},{"id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Kainrath","full_name":"Kainrath, Stephanie"},{"first_name":"Elliot J.","last_name":"Gerrard","full_name":"Gerrard, Elliot J."},{"id":"435ACB3A-F248-11E8-B48F-1D18A9856A87","first_name":"Priscila","full_name":"Hirschfeld, Priscila","last_name":"Hirschfeld"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan","last_name":"Schwarz","full_name":"Schwarz, Jan"},{"orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L","last_name":"Janovjak","full_name":"Janovjak, Harald L"}],"citation":{"mla":"Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” <i>Nature Communications</i>, vol. 9, no. 1, 1950, Springer Nature, 2018, doi:<a href=\"https://doi.org/10.1038/s41467-018-04342-1\">10.1038/s41467-018-04342-1</a>.","ista":"Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P, Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 9(1), 1950.","ama":"Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human class A orphan G-protein-coupled receptors. <i>Nature Communications</i>. 2018;9(1). doi:<a href=\"https://doi.org/10.1038/s41467-018-04342-1\">10.1038/s41467-018-04342-1</a>","short":"M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld, J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).","chicago":"Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” <i>Nature Communications</i>. Springer Nature, 2018. <a href=\"https://doi.org/10.1038/s41467-018-04342-1\">https://doi.org/10.1038/s41467-018-04342-1</a>.","ieee":"M. Morri <i>et al.</i>, “Optical functionalization of human class A orphan G-protein-coupled receptors,” <i>Nature Communications</i>, vol. 9, no. 1. Springer Nature, 2018.","apa":"Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J., Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class A orphan G-protein-coupled receptors. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-018-04342-1\">https://doi.org/10.1038/s41467-018-04342-1</a>"},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"project":[{"grant_number":"303564","call_identifier":"FP7","name":"Microbial Ion Channels for Synthetic Neurobiology","_id":"25548C20-B435-11E9-9278-68D0E5697425"},{"_id":"255A6082-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF","grant_number":"W1232-B24"}],"quality_controlled":"1","type":"journal_article","has_accepted_license":"1","publication_identifier":{"issn":["2041-1723"]},"article_number":"1950","issue":"1"},{"status":"public","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","file":[{"date_updated":"2020-07-14T12:47:15Z","access_level":"open_access","date_created":"2019-02-14T12:34:29Z","file_size":6668971,"creator":"kschuh","checksum":"e98465b4416b3e804c47f40086932af2","file_name":"2018_ASCB_Dolati.pdf","content_type":"application/pdf","relation":"main_file","file_id":"5994"}],"volume":29,"file_date_updated":"2020-07-14T12:47:15Z","publisher":"American Society for Cell Biology ","_id":"5992","author":[{"first_name":"Setareh","last_name":"Dolati","full_name":"Dolati, Setareh"},{"first_name":"Frieda","full_name":"Kage, Frieda","last_name":"Kage"},{"full_name":"Mueller, Jan","last_name":"Mueller","first_name":"Jan"},{"first_name":"Mathias","full_name":"Müsken, Mathias","last_name":"Müsken"},{"full_name":"Kirchner, Marieluise","last_name":"Kirchner","first_name":"Marieluise"},{"first_name":"Gunnar","last_name":"Dittmar","full_name":"Dittmar, Gunnar"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Klemens","full_name":"Rottner, Klemens","last_name":"Rottner"},{"full_name":"Falcke, Martin","last_name":"Falcke","first_name":"Martin"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"}],"date_published":"2018-11-01T00:00:00Z","day":"01","year":"2018","quality_controlled":"1","type":"journal_article","pmid":1,"citation":{"apa":"Dolati, S., Kage, F., Mueller, J., Müsken, M., Kirchner, M., Dittmar, G., … Falcke, M. (2018). On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. <i>Molecular Biology of the Cell</i>. American Society for Cell Biology . <a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">https://doi.org/10.1091/mbc.e18-02-0082</a>","ieee":"S. Dolati <i>et al.</i>, “On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility,” <i>Molecular Biology of the Cell</i>, vol. 29, no. 22. American Society for Cell Biology , pp. 2674–2686, 2018.","short":"S. Dolati, F. Kage, J. Mueller, M. Müsken, M. Kirchner, G. Dittmar, M.K. Sixt, K. Rottner, M. Falcke, Molecular Biology of the Cell 29 (2018) 2674–2686.","chicago":"Dolati, Setareh, Frieda Kage, Jan Mueller, Mathias Müsken, Marieluise Kirchner, Gunnar Dittmar, Michael K Sixt, Klemens Rottner, and Martin Falcke. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” <i>Molecular Biology of the Cell</i>. American Society for Cell Biology , 2018. <a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">https://doi.org/10.1091/mbc.e18-02-0082</a>.","ista":"Dolati S, Kage F, Mueller J, Müsken M, Kirchner M, Dittmar G, Sixt MK, Rottner K, Falcke M. 2018. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell. 29(22), 2674–2686.","ama":"Dolati S, Kage F, Mueller J, et al. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. <i>Molecular Biology of the Cell</i>. 2018;29(22):2674-2686. doi:<a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">10.1091/mbc.e18-02-0082</a>","mla":"Dolati, Setareh, et al. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” <i>Molecular Biology of the Cell</i>, vol. 29, no. 22, American Society for Cell Biology , 2018, pp. 2674–86, doi:<a href=\"https://doi.org/10.1091/mbc.e18-02-0082\">10.1091/mbc.e18-02-0082</a>."},"tmp":{"short":"CC BY-NC-SA (4.0)","image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"issue":"22","has_accepted_license":"1","publication_identifier":{"eissn":["1939-4586"]},"doi":"10.1091/mbc.e18-02-0082","title":"On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility","abstract":[{"text":"Lamellipodia are flat membrane protrusions formed during mesenchymal motion. Polymerization at the leading edge assembles the actin filament network and generates protrusion force. How this force is supported by the network and how the assembly rate is shared between protrusion and network retrograde flow determines the protrusion rate. We use mathematical modeling to understand experiments changing the F-actin density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction of density with a decrease of protrusion velocity, an increase in the ratio of force to filament number, but constant network assembly rate. The relation between protrusion force and tension gradient in the F-actin network and the density dependency of friction, elasticity, and viscosity of the network explain the experimental observations. The formins act as filament nucleators and elongators with differential rates. Modulation of their activity suggests an effect on network assembly rate. Contrary to these expectations, the effect of changes in elongator composition is much weaker than the consequences of the density change. We conclude that the force acting on the leading edge membrane is the force required to drive F-actin network retrograde flow.","lang":"eng"}],"external_id":{"pmid":["30156465"],"isi":["000455641000011"]},"scopus_import":"1","date_updated":"2023-09-19T14:30:23Z","publication_status":"published","language":[{"iso":"eng"}],"oa_version":"Published Version","oa":1,"intvolume":"        29","month":"11","isi":1,"ddc":["570"],"date_created":"2019-02-14T12:25:47Z","page":"2674-2686","publication":"Molecular Biology of the Cell"},{"corr_author":"1","month":"09","ddc":["570"],"date_created":"2019-04-29T09:40:33Z","publication":"Bio-Protocol","oa":1,"intvolume":"         8","publication_status":"published","date_updated":"2025-05-20T07:43:06Z","language":[{"iso":"eng"}],"oa_version":"Published Version","OA_place":"publisher","doi":"10.21769/bioprotoc.3018","DOAJ_listed":"1","external_id":{"pmid":["34395806"]},"title":"Platelet migration and bacterial trapping assay under flow","abstract":[{"lang":"eng","text":"Blood platelets are critical for hemostasis and thrombosis, but also play diverse roles during immune responses. We have recently reported that platelets migrate at sites of infection in vitro and in vivo. Importantly, platelets use their ability to migrate to collect and bundle fibrin (ogen)-bound bacteria accomplishing efficient intravascular bacterial trapping. Here, we describe a method that allows analyzing platelet migration in vitro, focusing on their ability to collect bacteria and trap bacteria under flow."}],"article_number":"e3018","issue":"18","keyword":["Platelets","Cell migration","Bacteria","Shear flow","Fibrinogen","E. coli"],"has_accepted_license":"1","publication_identifier":{"issn":["2331-8325"]},"pmid":1,"project":[{"grant_number":"747687","call_identifier":"H2020","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"}],"quality_controlled":"1","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","OA_type":"gold","citation":{"mla":"Fan, Shuxia, et al. “Platelet Migration and Bacterial Trapping Assay under Flow.” <i>Bio-Protocol</i>, vol. 8, no. 18, e3018, Bio-Protocol, 2018, doi:<a href=\"https://doi.org/10.21769/bioprotoc.3018\">10.21769/bioprotoc.3018</a>.","ista":"Fan S, Lorenz M, Massberg S, Gärtner FR. 2018. Platelet migration and bacterial trapping assay under flow. Bio-Protocol. 8(18), e3018.","ama":"Fan S, Lorenz M, Massberg S, Gärtner FR. Platelet migration and bacterial trapping assay under flow. <i>Bio-Protocol</i>. 2018;8(18). doi:<a href=\"https://doi.org/10.21769/bioprotoc.3018\">10.21769/bioprotoc.3018</a>","apa":"Fan, S., Lorenz, M., Massberg, S., &#38; Gärtner, F. R. (2018). Platelet migration and bacterial trapping assay under flow. <i>Bio-Protocol</i>. Bio-Protocol. <a href=\"https://doi.org/10.21769/bioprotoc.3018\">https://doi.org/10.21769/bioprotoc.3018</a>","ieee":"S. Fan, M. Lorenz, S. Massberg, and F. R. Gärtner, “Platelet migration and bacterial trapping assay under flow,” <i>Bio-Protocol</i>, vol. 8, no. 18. Bio-Protocol, 2018.","chicago":"Fan, Shuxia, Michael Lorenz, Steffen Massberg, and Florian R Gärtner. “Platelet Migration and Bacterial Trapping Assay under Flow.” <i>Bio-Protocol</i>. Bio-Protocol, 2018. <a href=\"https://doi.org/10.21769/bioprotoc.3018\">https://doi.org/10.21769/bioprotoc.3018</a>.","short":"S. Fan, M. Lorenz, S. Massberg, F.R. Gärtner, Bio-Protocol 8 (2018)."},"article_processing_charge":"Yes","_id":"6354","author":[{"first_name":"Shuxia","last_name":"Fan","full_name":"Fan, Shuxia"},{"last_name":"Lorenz","full_name":"Lorenz, Michael","first_name":"Michael"},{"full_name":"Massberg, Steffen","last_name":"Massberg","first_name":"Steffen"},{"last_name":"Gärtner","full_name":"Gärtner, Florian R","orcid":"0000-0001-6120-3723","first_name":"Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Bio-Protocol","date_published":"2018-09-20T00:00:00Z","day":"20","year":"2018","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"}],"acknowledgement":"This protocol was adapted from a previously published study (Gaertner et al., 2017). We thank Michael Lorenz for his excellent assistance in bacteria culture. This work was funded by the DFG SFB 914 (S.M. [B02 and Z01]), the DFG SFB 1123 (S.M. [B06]), the DFG FOR 2033 (S.M. and F.G.), the German Centre for Cardiovascular Research (DZHK) (MHA 1.4VD [S.M.]), FP7 program (project 260309, PRESTIGE [S.M.]), FöFoLe project 947 (F.G.), the Friedrich-Baur-Stiftung project 41/16 (F.G.), Marie Sklodowska Curie Individual Fellowship (EU project 747687, LamelliaActin [F.G.]).","volume":8,"file_date_updated":"2020-07-14T12:47:28Z","status":"public","ec_funded":1,"file":[{"access_level":"open_access","date_updated":"2020-07-14T12:47:28Z","file_size":2928337,"date_created":"2019-04-30T08:04:33Z","content_type":"application/pdf","checksum":"d4588377e789da7f360b553ae02c5119","file_name":"2018_BioProtocol_Fan.pdf","creator":"dernst","file_id":"6360","relation":"main_file"}]},{"citation":{"ieee":"F. Moalli <i>et al.</i>, “The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells,” <i>The Journal of Experimental Medicine</i>, vol. 2015, no. 7. Rockefeller University Press, pp. 1869–1890, 2018.","apa":"Moalli, F., Ficht, X., Germann, P., Vladymyrov, M., Stolp, B., de Vries, I., … Stein, J. V. (2018). The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1084/jem.20170896\">https://doi.org/10.1084/jem.20170896</a>","chicago":"Moalli, Federica, Xenia Ficht, Philipp Germann, Mykhailo Vladymyrov, Bettina Stolp, Ingrid de Vries, Ruth Lyck, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental Medicine</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1084/jem.20170896\">https://doi.org/10.1084/jem.20170896</a>.","short":"F. Moalli, X. Ficht, P. Germann, M. Vladymyrov, B. Stolp, I. de Vries, R. Lyck, J. Balmer, A. Fiocchi, M. Kreutzfeldt, D. Merkler, M. Iannacone, A. Ariga, M.H. Stoffel, J. Sharpe, M. Bähler, M.K. Sixt, A. Diz-Muñoz, J.V. Stein, The Journal of Experimental Medicine 2015 (2018) 1869–1890.","ama":"Moalli F, Ficht X, Germann P, et al. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. <i>The Journal of Experimental Medicine</i>. 2018;2015(7):1869–1890. doi:<a href=\"https://doi.org/10.1084/jem.20170896\">10.1084/jem.20170896</a>","ista":"Moalli F, Ficht X, Germann P, Vladymyrov M, Stolp B, de Vries I, Lyck R, Balmer J, Fiocchi A, Kreutzfeldt M, Merkler D, Iannacone M, Ariga A, Stoffel MH, Sharpe J, Bähler M, Sixt MK, Diz-Muñoz A, Stein JV. 2018. The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells. The Journal of Experimental Medicine. 2015(7), 1869–1890.","mla":"Moalli, Federica, et al. “The Rho Regulator Myosin IXb Enables Nonlymphoid Tissue Seeding of Protective CD8+T Cells.” <i>The Journal of Experimental Medicine</i>, vol. 2015, no. 7, Rockefeller University Press, 2018, pp. 1869–1890, doi:<a href=\"https://doi.org/10.1084/jem.20170896\">10.1084/jem.20170896</a>."},"tmp":{"short":"CC BY-NC-SA (4.0)","image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"type":"journal_article","quality_controlled":"1","publication_identifier":{"issn":["0022-1007"],"eissn":["1540-9538"]},"has_accepted_license":"1","issue":"7","file":[{"date_updated":"2020-07-14T12:47:32Z","access_level":"open_access","file_size":3841660,"date_created":"2019-05-28T12:40:05Z","creator":"kschuh","content_type":"application/pdf","file_name":"2018_rupress_Moalli.pdf","checksum":"86ae5331f9bfced9a6358a790a04bef4","relation":"main_file","file_id":"6498"}],"status":"public","file_date_updated":"2020-07-14T12:47:32Z","volume":2015,"department":[{"_id":"MiSi"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","day":"06","year":"2018","date_published":"2018-06-06T00:00:00Z","publisher":"Rockefeller University Press","_id":"6497","author":[{"last_name":"Moalli","full_name":"Moalli, Federica","first_name":"Federica"},{"last_name":"Ficht","full_name":"Ficht, Xenia","first_name":"Xenia"},{"last_name":"Germann","full_name":"Germann, Philipp","first_name":"Philipp"},{"first_name":"Mykhailo","last_name":"Vladymyrov","full_name":"Vladymyrov, Mykhailo"},{"first_name":"Bettina","full_name":"Stolp, Bettina","last_name":"Stolp"},{"last_name":"de Vries","full_name":"de Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid"},{"first_name":"Ruth","last_name":"Lyck","full_name":"Lyck, Ruth"},{"last_name":"Balmer","full_name":"Balmer, Jasmin","first_name":"Jasmin"},{"first_name":"Amleto","full_name":"Fiocchi, Amleto","last_name":"Fiocchi"},{"full_name":"Kreutzfeldt, Mario","last_name":"Kreutzfeldt","first_name":"Mario"},{"last_name":"Merkler","full_name":"Merkler, Doron","first_name":"Doron"},{"full_name":"Iannacone, Matteo","last_name":"Iannacone","first_name":"Matteo"},{"full_name":"Ariga, Akitaka","last_name":"Ariga","first_name":"Akitaka"},{"first_name":"Michael H.","last_name":"Stoffel","full_name":"Stoffel, Michael H."},{"last_name":"Sharpe","full_name":"Sharpe, James","first_name":"James"},{"last_name":"Bähler","full_name":"Bähler, Martin","first_name":"Martin"},{"orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K"},{"first_name":"Alba","full_name":"Diz-Muñoz, Alba","last_name":"Diz-Muñoz"},{"first_name":"Jens V.","full_name":"Stein, Jens V.","last_name":"Stein"}],"article_processing_charge":"No","intvolume":"      2015","oa":1,"page":"1869–1890","publication":"The Journal of Experimental Medicine","date_created":"2019-05-28T12:36:47Z","isi":1,"ddc":["570"],"month":"06","title":"The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells","abstract":[{"lang":"eng","text":"T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations."}],"external_id":{"isi":["000440822900011"]},"doi":"10.1084/jem.20170896","oa_version":"Published Version","language":[{"iso":"eng"}],"scopus_import":"1","publication_status":"published","date_updated":"2023-09-19T14:52:08Z"},{"external_id":{"isi":["000434963700016"]},"acknowledged_ssus":[{"_id":"SSU"}],"title":"Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration","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"}],"doi":"10.1002/eji.201747358","language":[{"iso":"eng"}],"oa_version":"Published Version","publication_status":"published","date_updated":"2025-04-14T07:42:07Z","scopus_import":"1","intvolume":"        48","oa":1,"date_created":"2018-12-11T11:46:28Z","publication":"European Journal of Immunology","page":"1074 - 1077","corr_author":"1","month":"02","ddc":["570"],"isi":1,"file_date_updated":"2020-07-14T12:46:27Z","volume":48,"ec_funded":1,"status":"public","file":[{"date_updated":"2020-07-14T12:46:27Z","access_level":"open_access","date_created":"2018-12-12T10:13:56Z","file_size":590106,"creator":"system","content_type":"application/pdf","checksum":"9d5b74cd016505aeb9a4c2d33bbedaeb","file_name":"IST-2018-1067-v1+2_Leithner_et_al-2018-European_Journal_of_Immunology.pdf","relation":"main_file","file_id":"5044"}],"license":"https://creativecommons.org/licenses/by-nc/4.0/","publist_id":"7386","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.   ","date_published":"2018-02-13T00:00:00Z","pubrep_id":"1067","year":"2018","day":"13","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"},{"_id":"Bio"}],"article_processing_charge":"Yes (via OA deal)","_id":"437","author":[{"orcid":"0000-0002-1073-744X","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","last_name":"Leithner","full_name":"Leithner, Alexander F"},{"last_name":"Renkawitz","full_name":"Renkawitz, Jörg","orcid":"0000-0003-2856-3369","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","first_name":"Jörg"},{"full_name":"De Vries, Ingrid","last_name":"De Vries","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","first_name":"Ingrid"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","last_name":"Hauschild"},{"last_name":"Haecker","full_name":"Haecker, Hans","first_name":"Hans"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"}],"publisher":"Wiley-Blackwell","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"citation":{"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.” <i>European Journal of Immunology</i>. Wiley-Blackwell, 2018. <a href=\"https://doi.org/10.1002/eji.201747358\">https://doi.org/10.1002/eji.201747358</a>.","short":"A.F. Leithner, J. Renkawitz, I. de Vries, R. Hauschild, H. Haecker, M.K. Sixt, European Journal of Immunology 48 (2018) 1074–1077.","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,” <i>European Journal of Immunology</i>, vol. 48, no. 6. Wiley-Blackwell, pp. 1074–1077, 2018.","apa":"Leithner, A. F., Renkawitz, J., de Vries, I., Hauschild, R., Haecker, H., &#38; Sixt, M. K. (2018). Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration. <i>European Journal of Immunology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1002/eji.201747358\">https://doi.org/10.1002/eji.201747358</a>","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. <i>European Journal of Immunology</i>. 2018;48(6):1074-1077. doi:<a href=\"https://doi.org/10.1002/eji.201747358\">10.1002/eji.201747358</a>","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.","mla":"Leithner, Alexander F., et al. “Fast and Efficient Genetic Engineering of Hematopoietic Precursor Cells for the Study of Dendritic Cell Migration.” <i>European Journal of Immunology</i>, vol. 48, no. 6, Wiley-Blackwell, 2018, pp. 1074–77, doi:<a href=\"https://doi.org/10.1002/eji.201747358\">10.1002/eji.201747358</a>."},"quality_controlled":"1","project":[{"grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"type":"journal_article","has_accepted_license":"1","issue":"6"},{"publication_identifier":{"issn":["0022-1007"]},"has_accepted_license":"1","issue":"12","citation":{"mla":"Reversat, Anne, and Michael K. Sixt. “IgM’s Exit Route.” <i>Journal of Experimental Medicine</i>, vol. 215, no. 12, Rockefeller University Press, 2018, pp. 2959–61, doi:<a href=\"https://doi.org/10.1084/jem.20181934\">10.1084/jem.20181934</a>.","ieee":"A. Reversat and M. K. Sixt, “IgM’s exit route,” <i>Journal of Experimental Medicine</i>, vol. 215, no. 12. Rockefeller University Press, pp. 2959–2961, 2018.","apa":"Reversat, A., &#38; Sixt, M. K. (2018). IgM’s exit route. <i>Journal of Experimental Medicine</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1084/jem.20181934\">https://doi.org/10.1084/jem.20181934</a>","short":"A. Reversat, M.K. Sixt, Journal of Experimental Medicine 215 (2018) 2959–2961.","chicago":"Reversat, Anne, and Michael K Sixt. “IgM’s Exit Route.” <i>Journal of Experimental Medicine</i>. Rockefeller University Press, 2018. <a href=\"https://doi.org/10.1084/jem.20181934\">https://doi.org/10.1084/jem.20181934</a>.","ama":"Reversat A, Sixt MK. IgM’s exit route. <i>Journal of Experimental Medicine</i>. 2018;215(12):2959-2961. doi:<a href=\"https://doi.org/10.1084/jem.20181934\">10.1084/jem.20181934</a>","ista":"Reversat A, Sixt MK. 2018. IgM’s exit route. Journal of Experimental Medicine. 215(12), 2959–2961."},"tmp":{"short":"CC BY-NC-SA (4.0)","image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"type":"journal_article","quality_controlled":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","department":[{"_id":"MiSi"}],"day":"20","year":"2018","date_published":"2018-11-20T00:00:00Z","publisher":"Rockefeller University Press","article_processing_charge":"No","_id":"5672","author":[{"id":"35B76592-F248-11E8-B48F-1D18A9856A87","first_name":"Anne","orcid":"0000-0003-0666-8928","full_name":"Reversat, Anne","last_name":"Reversat"},{"full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"file":[{"date_created":"2019-02-06T08:49:52Z","file_size":1216437,"access_level":"open_access","date_updated":"2020-07-14T12:47:09Z","file_id":"5931","relation":"main_file","checksum":"687beea1d64c213f4cb9e3c29ec11a14","content_type":"application/pdf","file_name":"2018_JournalExperMed_Reversat.pdf","creator":"dernst"}],"status":"public","volume":215,"file_date_updated":"2020-07-14T12:47:09Z","page":"2959-2961","publication":"Journal of Experimental Medicine","date_created":"2018-12-16T22:59:18Z","isi":1,"ddc":["570"],"month":"11","intvolume":"       215","oa":1,"oa_version":"Published Version","language":[{"iso":"eng"}],"scopus_import":"1","date_updated":"2026-04-16T09:54:07Z","publication_status":"published","title":"IgM's exit route","abstract":[{"lang":"eng","text":"The release of IgM is the first line of an antibody response and precedes the generation of high affinity IgG in germinal centers. Once secreted by freshly activated plasmablasts, IgM is released into the efferent lymph of reactive lymph nodes as early as 3 d after immunization. As pentameric IgM has an enormous size of 1,000 kD, its diffusibility is low, and one might wonder how it can pass through the densely lymphocyte-packed environment of a lymph node parenchyma in order to reach its exit. In this issue of JEM, Thierry et al. show that, in order to reach the blood stream, IgM molecules take a specific micro-anatomical route via lymph node conduits."}],"external_id":{"isi":["000451920600002"]},"doi":"10.1084/jem.20181934"},{"citation":{"mla":"Leithner, Alexander F. <i>Branched Actin Networks in Dendritic Cell Biology</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>.","ieee":"A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute of Science and Technology Austria, 2018.","apa":"Leithner, A. F. (2018). <i>Branched actin networks in dendritic cell biology</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>","chicago":"Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">https://doi.org/10.15479/AT:ISTA:th_998</a>.","short":"A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute of Science and Technology Austria, 2018.","ama":"Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_998\">10.15479/AT:ISTA:th_998</a>","ista":"Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"dissertation","publication_identifier":{"issn":["2663-337X"]},"has_accepted_license":"1","related_material":{"record":[{"id":"1321","relation":"part_of_dissertation","status":"public"}]},"file":[{"creator":"dernst","checksum":"d5e3edbac548c26c1fa43a4b37a54a4c","file_name":"PhD_thesis_AlexLeithner_final_version.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","embargo_to":"open_access","file_id":"6219","date_updated":"2021-02-11T23:30:17Z","access_level":"closed","date_created":"2019-04-05T09:23:11Z","file_size":29027671},{"file_size":66045341,"date_created":"2019-04-05T09:23:11Z","date_updated":"2021-02-11T11:17:16Z","access_level":"open_access","relation":"main_file","embargo":"2019-04-15","file_id":"6220","creator":"dernst","content_type":"application/pdf","checksum":"071f7476db29e41146824ebd0697cb10","file_name":"PhD_thesis_AlexLeithner.pdf"}],"status":"public","file_date_updated":"2021-02-11T23:30:17Z","acknowledgement":"First of all I would like to thank Michael Sixt for giving me the opportunity to work in \r\nhis group and for his support throughout the years. He is a truly inspiring person and \r\nthe  best  boss  one  can  imagine.  I  would  also  like  to  thank  all  current  and  past \r\nmembers of the Sixt group for their help and the great working atmosphere in the lab. \r\nIt is a true privilege to work with such a bright, funny and friendly group of people and \r\nI’m  proud  that  I  could  be  part  of  it.  Furthermore,  I  would  like  to  say  ‘thank  you’  to Daria Siekhaus for all the meetings and discussion we had throughout the years \r\nand to  Federica  Benvenuti  for  being  part  of  my  committee.  I  am  also  grateful  to  Jack \r\nMerrin  in  the  nanofabrication  facility  and  all  the  people  working  in  the  bioimaging-\r\n, the electron microscopy- and the preclinical facilities.","publist_id":"7542","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"}],"day":"12","year":"2018","pubrep_id":"998","date_published":"2018-04-12T00:00:00Z","publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"article_processing_charge":"No","_id":"323","author":[{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X"}],"oa":1,"page":"99","date_created":"2018-12-11T11:45:49Z","ddc":["571","599","610"],"month":"04","corr_author":"1","supervisor":[{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"}],"degree_awarded":"PhD","acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"abstract":[{"text":"In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. ","lang":"eng"}],"title":"Branched actin networks in dendritic cell biology","doi":"10.15479/AT:ISTA:th_998","oa_version":"Published Version","language":[{"iso":"eng"}],"publication_status":"published","date_updated":"2025-09-22T08:27:34Z"},{"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).","publist_id":"8040","status":"public","ec_funded":1,"volume":19,"publisher":"Nature Publishing Group","_id":"15","article_processing_charge":"No","author":[{"last_name":"Hons","full_name":"Hons, Miroslav","orcid":"0000-0002-6625-3348","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","first_name":"Miroslav"},{"last_name":"Kopf","full_name":"Kopf, Aglaja","orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","first_name":"Aglaja"},{"orcid":"0000-0001-9843-3522","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","last_name":"Leithner"},{"id":"397A88EE-F248-11E8-B48F-1D18A9856A87","first_name":"Florian R","orcid":"0000-0001-6120-3723","full_name":"Gärtner, Florian R","last_name":"Gärtner"},{"first_name":"Jun","full_name":"Abe, Jun","last_name":"Abe"},{"first_name":"Jörg","id":"3F0587C8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2856-3369","full_name":"Renkawitz, Jörg","last_name":"Renkawitz"},{"first_name":"Jens","last_name":"Stein","full_name":"Stein, Jens"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","full_name":"Sixt, Michael K"}],"department":[{"_id":"MiSi"},{"_id":"Bio"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2018","day":"18","date_published":"2018-05-18T00:00:00Z","type":"journal_article","project":[{"call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"},{"call_identifier":"H2020","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","grant_number":"747687"},{"grant_number":"ALTF 1396-2014","name":"Molecular and system level view of immune cell migration","_id":"25A48D24-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A603A2-B435-11E9-9278-68D0E5697425","grant_number":"281556"}],"quality_controlled":"1","pmid":1,"citation":{"mla":"Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” <i>Nature Immunology</i>, vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:<a href=\"https://doi.org/10.1038/s41590-018-0109-z\">10.1038/s41590-018-0109-z</a>.","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.","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. <i>Nature Immunology</i>. 2018;19(6):606-616. doi:<a href=\"https://doi.org/10.1038/s41590-018-0109-z\">10.1038/s41590-018-0109-z</a>","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.","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.” <i>Nature Immunology</i>. Nature Publishing Group, 2018. <a href=\"https://doi.org/10.1038/s41590-018-0109-z\">https://doi.org/10.1038/s41590-018-0109-z</a>.","ieee":"M. Hons <i>et al.</i>, “Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells,” <i>Nature Immunology</i>, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.","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. <i>Nature Immunology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41590-018-0109-z\">https://doi.org/10.1038/s41590-018-0109-z</a>"},"issue":"6","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/29777221","open_access":"1"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"6891"}]},"doi":"10.1038/s41590-018-0109-z","acknowledged_ssus":[{"_id":"SSU"}],"abstract":[{"lang":"eng","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."}],"title":"Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells","external_id":{"pmid":["29777221"],"isi":["000433041500026"]},"scopus_import":"1","date_updated":"2026-06-05T22:32:58Z","publication_status":"published","oa_version":"Published Version","language":[{"iso":"eng"}],"oa":1,"intvolume":"        19","isi":1,"month":"05","page":"606 - 616","publication":"Nature Immunology","date_created":"2018-12-11T11:44:10Z"},{"language":[{"iso":"eng"}],"oa_version":"Published Version","scopus_import":"1","date_updated":"2026-06-05T22:34:18Z","publication_status":"published","abstract":[{"text":"During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"}],"title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","external_id":{"isi":["000428043600047"],"pmid":["29567714"]},"doi":"10.1126/science.aal3662","date_created":"2018-12-11T11:46:16Z","page":"1408 - 1411","publication":"Science","month":"03","isi":1,"corr_author":"1","intvolume":"       359","oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"}],"date_published":"2018-03-23T00:00:00Z","year":"2018","day":"23","publisher":"American Association for the Advancement of Science","_id":"402","author":[{"last_name":"Brown","full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus"},{"full_name":"Assen, Frank P","last_name":"Assen","first_name":"Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119"},{"last_name":"Leithner","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F"},{"first_name":"Jun","last_name":"Abe","full_name":"Abe, Jun"},{"full_name":"Schachner, Helga","last_name":"Schachner","first_name":"Helga"},{"full_name":"Asfour, Gabriele","last_name":"Asfour","first_name":"Gabriele"},{"last_name":"Bagó Horváth","full_name":"Bagó Horváth, Zsuzsanna","first_name":"Zsuzsanna"},{"first_name":"Jens","last_name":"Stein","full_name":"Stein, Jens"},{"first_name":"Pavel","last_name":"Uhrin","full_name":"Uhrin, Pavel"},{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-6620-9179"},{"last_name":"Kerjaschki","full_name":"Kerjaschki, Dontscho","first_name":"Dontscho"}],"article_processing_charge":"No","ec_funded":1,"status":"public","volume":359,"acknowledgement":"M.B. was supported by the Cell Communication in Health and Disease graduate study program of the Austrian Science Fund (FWF) and the Medical University of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556) and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging, the Sixt lab for intellectual input, M. Schunn for help with the design of the in vivo experiments, F. Langer for technical assistance with the in vivo experiments, the bioimaging facility of IST Austria for support, and R. Efferl for providing the CT26 cell line.","publist_id":"7428","issue":"6382","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1126/science.aal3662"}],"related_material":{"record":[{"id":"6947","relation":"dissertation_contains","status":"public"}]},"citation":{"short":"M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z. Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018) 1408–1411.","chicago":"Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner, Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>. American Association for the Advancement of Science, 2018. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>.","ieee":"M. Brown <i>et al.</i>, “Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice,” <i>Science</i>, vol. 359, no. 6382. American Association for the Advancement of Science, pp. 1408–1411, 2018.","apa":"Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G., … Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.aal3662\">https://doi.org/10.1126/science.aal3662</a>","ista":"Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382), 1408–1411.","ama":"Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. <i>Science</i>. 2018;359(6382):1408-1411. doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>","mla":"Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” <i>Science</i>, vol. 359, no. 6382, American Association for the Advancement of Science, 2018, pp. 1408–11, doi:<a href=\"https://doi.org/10.1126/science.aal3662\">10.1126/science.aal3662</a>."},"article_type":"original","quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12"},{"call_identifier":"FP7","_id":"25A603A2-B435-11E9-9278-68D0E5697425","name":"Cytoskeletal force generation and force transduction of migrating leukocytes","grant_number":"281556"}],"type":"journal_article","pmid":1},{"intvolume":"        27","oa":1,"publication":"Current Biology","page":"R24 - R25","date_created":"2018-12-11T11:50:29Z","isi":1,"month":"01","title":"Cell migration: Making the waves","abstract":[{"lang":"eng","text":"Coordinated changes of cell shape are often the result of the excitable, wave-like dynamics of the actin cytoskeleton. New work shows that, in migrating cells, protrusion waves arise from mechanochemical crosstalk between adhesion sites, membrane tension and the actin protrusive machinery."}],"external_id":{"isi":["000391902500010"]},"doi":"10.1016/j.cub.2016.11.035","OA_place":"publisher","oa_version":"Published Version","language":[{"iso":"eng"}],"scopus_import":"1","publication_status":"published","date_updated":"2025-06-26T09:01:10Z","citation":{"ista":"Müller J, Sixt MK. 2017. Cell migration: Making the waves. Current Biology. 27(1), R24–R25.","ama":"Müller J, Sixt MK. Cell migration: Making the waves. <i>Current Biology</i>. 2017;27(1):R24-R25. doi:<a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">10.1016/j.cub.2016.11.035</a>","short":"J. Müller, M.K. Sixt, Current Biology 27 (2017) R24–R25.","chicago":"Müller, Jan, and Michael K Sixt. “Cell Migration: Making the Waves.” <i>Current Biology</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">https://doi.org/10.1016/j.cub.2016.11.035</a>.","ieee":"J. Müller and M. K. Sixt, “Cell migration: Making the waves,” <i>Current Biology</i>, vol. 27, no. 1. Cell Press, pp. R24–R25, 2017.","apa":"Müller, J., &#38; Sixt, M. K. (2017). Cell migration: Making the waves. <i>Current Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">https://doi.org/10.1016/j.cub.2016.11.035</a>","mla":"Müller, Jan, and Michael K. Sixt. “Cell Migration: Making the Waves.” <i>Current Biology</i>, vol. 27, no. 1, Cell Press, 2017, pp. R24–25, doi:<a href=\"https://doi.org/10.1016/j.cub.2016.11.035\">10.1016/j.cub.2016.11.035</a>."},"article_type":"letter_note","OA_type":"free access","type":"journal_article","quality_controlled":"1","publication_identifier":{"issn":["09609822"]},"issue":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cub.2016.11.035"}],"status":"public","volume":27,"publist_id":"6197","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"}],"year":"2017","day":"09","date_published":"2017-01-09T00:00:00Z","publisher":"Cell Press","author":[{"full_name":"Müller, Jan","last_name":"Müller","first_name":"Jan","id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"_id":"1161","article_processing_charge":"No"}]