{"degree_awarded":"PhD","corr_author":"1","type":"dissertation","title":"Coordination of protrusive forces in immune cell migration ","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"10703"},{"id":"20082","relation":"part_of_dissertation","status":"public"}]},"has_accepted_license":"1","oa":1,"status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"file_date_updated":"2025-08-27T13:02:28Z","OA_place":"repository","author":[{"last_name":"Dos Reis Rodrigues","orcid":"0000-0003-1681-508X","first_name":"Patricia","full_name":"Dos Reis Rodrigues, Patricia","id":"26E95904-5160-11E9-9C0B-C5B0DC97E90F"}],"date_updated":"2025-09-30T14:09:06Z","project":[{"_id":"bd91e723-d553-11ed-ba76-fe7eeb2185fd","name":"Pushing from within: Control of cell shape, integrity and motility by cytoskeletal pushing forces","grant_number":"101071793"}],"day":"08","doi":"10.15479/AT-ISTA-20149","publisher":"Institute of Science and Technology Austria","publication_status":"published","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"NanoFab"}],"acknowledgement":"I would like to acknowledge the\r\nfinancial support of the European Research Council through the ERC-SyG grant “Pushing from\r\nwithin: Control of cell shape, integrity and motility by cytoskeletal pushing forces”\r\n(01071793), which made this research possible. ","date_published":"2025-08-08T00:00:00Z","date_created":"2025-08-08T09:18:02Z","oa_version":"Published Version","department":[{"_id":"GradSch"},{"_id":"MiSi"}],"article_processing_charge":"No","abstract":[{"text":"Immune responses depend on the coordinated and efficient migration of leukocytes. These\r\ncells, which are embedded and tightly confined within tissues, must navigate and traverse\r\ndiverse and complex three-dimensional environments. Leukocytes adapt their locomotory\r\nbehavior to the mechanical, geometrical, and biochemical characteristics of their\r\nsurroundings. In low-density environments, where the pore size of the interstitial matrix\r\nallows free passage, these cells position the nucleus directly behind the lamellipodium, the\r\nprotrusive actin structure that forms the leading front of the cell. In this configuration, they\r\nuse the nucleus as a gauge to identify the path of least resistance.\r\nHere, we show that in high-density environments, where the pore size precludes free passage\r\nof the cell body, leukocytes reposition the microtubule-organizing center (MTOC) and\r\nassociated organelles in front of the nucleus. In this configuration, they use actin structures\r\nprotruding orthogonally to the direction of migration in order to open a path for the cell body.\r\nWe identify two distinct actin populations that serve this purpose at different subcellular\r\nlocalizations. At the leading edge, local indentation of the plasma membrane leads to\r\nrecruitment of the Wiskott-Aldrich syndrome protein (WASp), which, via Arp2/3, results in\r\nthe formation of individual actin foci. At the cell body, actin polymerization is triggered by\r\nDOCK8, a Cdc42 exchange factor, resulting in the formation of a central actin pool.\r\nWe demonstrate that the central and peripheral actin pools are functionally communicating\r\nand that depletion of the central actin pool leads to increased actin accumulation at the cell\r\nfront, resulting in excessive extension of the leading edge.","lang":"eng"}],"_id":"20149","file":[{"content_type":"application/pdf","file_name":"2025_ReisRodrigues_Patricia_Thesis.pdf","creator":"prodrigu","success":1,"file_size":63885565,"file_id":"20232","date_updated":"2025-08-27T12:59:10Z","checksum":"fda8a1070667c3562263f4867609b41b","relation":"main_file","access_level":"open_access","date_created":"2025-08-27T12:59:10Z"},{"access_level":"closed","date_created":"2025-08-27T13:00:30Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"2025_ReisRodrigues_Patricia_Thesis.docx","creator":"prodrigu","file_size":50483434,"file_id":"20233","checksum":"e8b65affcbce846a926454df4b2867b9","date_updated":"2025-08-27T13:02:28Z","relation":"source_file"}],"publication_identifier":{"issn":["2663-337X"]},"year":"2025","language":[{"iso":"eng"}],"citation":{"ista":"Dos Reis Rodrigues P. 2025. Coordination of protrusive forces in immune cell migration . Institute of Science and Technology Austria.","ama":"Dos Reis Rodrigues P. Coordination of protrusive forces in immune cell migration . 2025. doi:10.15479/AT-ISTA-20149","short":"P. Dos Reis Rodrigues, Coordination of Protrusive Forces in Immune Cell Migration , Institute of Science and Technology Austria, 2025.","chicago":"Dos Reis Rodrigues, Patricia. “Coordination of Protrusive Forces in Immune Cell Migration .” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20149.","mla":"Dos Reis Rodrigues, Patricia. Coordination of Protrusive Forces in Immune Cell Migration . Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20149.","apa":"Dos Reis Rodrigues, P. (2025). Coordination of protrusive forces in immune cell migration . Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20149","ieee":"P. Dos Reis Rodrigues, “Coordination of protrusive forces in immune cell migration ,” Institute of Science and Technology Austria, 2025."},"ddc":["570"],"alternative_title":["ISTA Thesis"],"page":"114","month":"08","supervisor":[{"orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}]}