[{"type":"dissertation","abstract":[{"text":"Cell migration is a crucial process in animal development and maintenance. It is incredibly\r\nheterogeneous, with different cell types utilizing fundamentally distinct migration strategies.\r\nThe strategies also depend on the cellular microenvironment, where cells can switch between\r\nmigration modes as they encounter new environmental cues. In this thesis, we investigated\r\nhow dendritic cells adapt their migration strategy when encountering geometrically,\r\nmechanically and chemically distinct environments.\r\nWhen dendritic cells are embedded in a homogeneous fibrous network, they migrate in a fast\r\nand directional amoeboid manner. In this migration strategy, extracellular proteolysis and\r\nintegrin-mediated adhesions are dispensable. Instead, the cells use topography of the\r\nenvironment to propel their cell body forward. To migrate efficiently in the maze of different\r\npore sizes, they position the nucleus ahead of the microtubule organizing center (MTOC) and\r\nuse it to gauge the pores to identify the path of least resistance. Our aim was to identify\r\nwhether dendritic cells adapt their migration strategy when encountering asymmetrical\r\ntransitions into much denser environments with limited choice of large pores. In such invasive\r\ntransitions it is unclear if the cells can cross tight pores without the use of adhesions and\r\nextracellular proteolysis and whether they maintain the nucleus in the cell front.\r\nUsing various cell migration assays such as fibrous 3D collagen gels, geometrically defined\r\nmicrochannels with constrictions and simplistic under agarose migration assay, we provide\r\na comprehensive characterization of invasive migration of dendritic cells. We show that\r\nduring invasion the cells stall and stretch, reflecting the difficulty to translocate the bulky cell\r\nbody into the dense environment. In collagen gels, we show that dendritic cells can invade\r\nwithout proteolysis and adhesions. Instead, they utilize contractility, which can lead to largescale collagen compressions. During invasion, the nucleus stalls at tight constrictions, leading\r\nto a transient organelle reorientation. To resolve the stalling, upregulated rear contractility is\r\nrequired. This contractile force is simultaneously necessary for reverting the nucleus back to\r\nthe cell front after invasion and maintaining this positioning during permissive migration.\r\nA functional role of the reorientation was uncovered in the first collaboration project.\r\nA prominent central actin pool was identified around the MTOC, especially pronounced in\r\ndense and compressive environments. The actin pool was shown to generate pushing forces\r\nto dilate the space for cell translocation. These forces are only necessary in non-permissive\r\nenvironments, where the nucleus reorients to the cell rear, allowing the actin pool to\r\ngenerate space. In permissive environments where space generation is dispensable, the\r\nMTOC is located behind the nucleus and the actin cloud has reduced intensity, allowing more\r\nactin to be incorporated into the lamellipodium, speeding up migration.\r\nIn the second collaboration project, we investigated the effects of distinct chemical\r\nenvironments on dendritic cell migration. The strikingly persistent migration of these cells\r\nwas explained by their ability to modulate and even self-generate chemokine gradients. This\r\nallows the cells to migrate faster and more persistent in uniform chemokine fields compared\r\nto imposed chemokine gradients. The chemokine receptor CCR7 was identified as a crucial\r\nplayer in this process, both sensing the signal and internalizing the chemokine to create a sink.","lang":"eng"}],"citation":{"chicago":"Canigova, Nikola. “Adaptive Strategies of Dendritic Cell Migration in Response to Environmental Cues.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-19745\">https://doi.org/10.15479/AT-ISTA-19745</a>.","ista":"Canigova N. 2025. Adaptive strategies of dendritic cell migration in response to environmental cues. Institute of Science and Technology Austria.","mla":"Canigova, Nikola. <i>Adaptive Strategies of Dendritic Cell Migration in Response to Environmental Cues</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19745\">10.15479/AT-ISTA-19745</a>.","ama":"Canigova N. Adaptive strategies of dendritic cell migration in response to environmental cues. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19745\">10.15479/AT-ISTA-19745</a>","apa":"Canigova, N. (2025). <i>Adaptive strategies of dendritic cell migration in response to environmental cues</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-19745\">https://doi.org/10.15479/AT-ISTA-19745</a>","ieee":"N. Canigova, “Adaptive strategies of dendritic cell migration in response to environmental cues,” Institute of Science and Technology Austria, 2025.","short":"N. Canigova, Adaptive Strategies of Dendritic Cell Migration in Response to Environmental Cues, Institute of Science and Technology Austria, 2025."},"publisher":"Institute of Science and Technology Austria","corr_author":"1","department":[{"_id":"MiSi"},{"_id":"GradSch"}],"alternative_title":["ISTA Thesis"],"publication_status":"published","date_created":"2025-05-26T08:49:00Z","month":"05","OA_embargo":"6","_id":"19745","degree_awarded":"PhD","ec_funded":1,"acknowledgement":"This project has received funding from the Austrian Science Fund (FWF) via the doctorate\r\ncollege DK NanoCell and from the European Union’s Horizon 2020 research and innovation\r\nprogramme under the Marie Skłodowska-Curie Grant Agreement No. 665385.\r\n","publication_identifier":{"isbn":["978-3-99078-058-9"],"issn":["2663-337X"]},"year":"2025","doi":"10.15479/AT-ISTA-19745","day":"27","file":[{"file_id":"19748","date_updated":"2025-11-27T23:30:02Z","relation":"source_file","checksum":"1a2d1525d19347fbb879ef57c02951bf","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":103879193,"creator":"cchlebak","date_created":"2025-05-28T07:38:17Z","file_name":"NikolaCanigova_Thesis_final.docx","access_level":"closed","embargo_to":"open_access"},{"access_level":"open_access","date_created":"2025-05-28T07:39:53Z","file_name":"NikolaCanigova_Thesis_final_PDFA2a_fixed.pdf","embargo":"2025-11-27","creator":"cchlebak","file_size":194530600,"checksum":"c1d8f9a40a8e19fcf895373f4b773a46","content_type":"application/pdf","relation":"main_file","date_updated":"2025-11-27T23:30:02Z","file_id":"19749"}],"oa":1,"date_published":"2025-05-27T00:00:00Z","project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020"},{"call_identifier":"FWF","name":"Nano-Analytics of Cellular Systems","_id":"265E2996-B435-11E9-9278-68D0E5697425","grant_number":"W01250-B20"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","ddc":["570"],"supervisor":[{"first_name":"Michael K","full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"oa_version":"Published Version","language":[{"iso":"eng"}],"status":"public","file_date_updated":"2025-11-27T23:30:02Z","has_accepted_license":"1","article_processing_charge":"No","author":[{"first_name":"Nikola","orcid":"0000-0002-8518-5926","full_name":"Canigova, Nikola","last_name":"Canigova","id":"3795523E-F248-11E8-B48F-1D18A9856A87"}],"title":"Adaptive strategies of dendritic cell migration in response to environmental cues","page":"133","related_material":{"record":[{"status":"public","id":"14274","relation":"part_of_dissertation"}]},"date_updated":"2026-04-07T12:38:44Z"}]