--- _id: '12119' abstract: - lang: eng text: Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events. acknowledgement: "We thank Coung Kieu and Dominik van den Heuvel for excellent technical assistance. This work was supported by the German Research Foundation (PE2704/2-1, PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR 332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12 to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G. was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’ by the German Federal\r\nMinistry of Education and Research to the German Center for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care through the research project DigiMed Bayern." article_processing_charge: No article_type: original author: - first_name: Tobias full_name: Petzold, Tobias last_name: Petzold - first_name: Zhe full_name: Zhang, Zhe last_name: Zhang - first_name: Iván full_name: Ballesteros, Iván last_name: Ballesteros - first_name: Inas full_name: Saleh, Inas last_name: Saleh - first_name: Amin full_name: Polzin, Amin last_name: Polzin - first_name: Manuela full_name: Thienel, Manuela last_name: Thienel - first_name: Lulu full_name: Liu, Lulu last_name: Liu - first_name: Qurrat full_name: Ul Ain, Qurrat last_name: Ul Ain - first_name: Vincent full_name: Ehreiser, Vincent last_name: Ehreiser - first_name: Christian full_name: Weber, Christian last_name: Weber - first_name: Badr full_name: Kilani, Badr last_name: Kilani - first_name: Pontus full_name: Mertsch, Pontus last_name: Mertsch - first_name: Jeremias full_name: Götschke, Jeremias last_name: Götschke - first_name: Sophie full_name: Cremer, Sophie last_name: Cremer - first_name: Wenwen full_name: Fu, Wenwen last_name: Fu - first_name: Michael full_name: Lorenz, Michael last_name: Lorenz - first_name: Hellen full_name: Ishikawa-Ankerhold, Hellen last_name: Ishikawa-Ankerhold - first_name: Elisabeth full_name: Raatz, Elisabeth last_name: Raatz - first_name: Shaza full_name: El-Nemr, Shaza last_name: El-Nemr - first_name: Agnes full_name: Görlach, Agnes last_name: Görlach - first_name: Esther full_name: Marhuenda, Esther last_name: Marhuenda - first_name: Konstantin full_name: Stark, Konstantin last_name: Stark - first_name: Joachim full_name: Pircher, Joachim last_name: Pircher - first_name: David full_name: Stegner, David last_name: Stegner - first_name: Christian full_name: Gieger, Christian last_name: Gieger - first_name: Marc full_name: Schmidt-Supprian, Marc last_name: Schmidt-Supprian - first_name: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 - first_name: Isaac full_name: Almendros, Isaac last_name: Almendros - first_name: Malte full_name: Kelm, Malte last_name: Kelm - first_name: Christian full_name: Schulz, Christian last_name: Schulz - first_name: Andrés full_name: Hidalgo, Andrés last_name: Hidalgo - first_name: Steffen full_name: Massberg, Steffen last_name: Massberg citation: ama: Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 2022;55(12):2285-2299.e7. doi:10.1016/j.immuni.2022.10.001 apa: Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M., … Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2022.10.001 chicago: Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin, Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity. Elsevier, 2022. https://doi.org/10.1016/j.immuni.2022.10.001. ieee: T. Petzold et al., “Neutrophil ‘plucking’ on megakaryocytes drives platelet production and boosts cardiovascular disease,” Immunity, vol. 55, no. 12. Elsevier, p. 2285–2299.e7, 2022. ista: Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 55(12), 2285–2299.e7. mla: Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity, vol. 55, no. 12, Elsevier, 2022, p. 2285–2299.e7, doi:10.1016/j.immuni.2022.10.001. short: T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L. Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S. Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach, E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian, F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity 55 (2022) 2285–2299.e7. date_created: 2023-01-12T11:56:54Z date_published: 2022-12-13T00:00:00Z date_updated: 2023-08-03T14:21:51Z day: '13' ddc: - '570' department: - _id: MiSi doi: 10.1016/j.immuni.2022.10.001 ec_funded: 1 external_id: isi: - '000922019600003' pmid: - '36272416' file: - access_level: open_access checksum: 073267a9c0ad9f85a650053bc7b23777 content_type: application/pdf creator: dernst date_created: 2023-01-23T10:18:48Z date_updated: 2023-01-23T10:18:48Z file_id: '12341' file_name: 2022_Immunity_Petzold.pdf file_size: 5299475 relation: main_file success: 1 file_date_updated: 2023-01-23T10:18:48Z has_accepted_license: '1' intvolume: ' 55' isi: 1 issue: '12' keyword: - Infectious Diseases - Immunology - Immunology and Allergy language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '12' oa: 1 oa_version: Published Version page: 2285-2299.e7 pmid: 1 project: - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells publication: Immunity publication_identifier: issn: - 1074-7613 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease tmp: image: /images/cc_by_nc_nd.png 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) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 55 year: '2022' ... --- _id: '12133' abstract: - lang: eng text: Social distancing is an effective way to prevent the spread of disease in societies, whereas infection elimination is a key element of organismal immunity. Here, we discuss how the study of social insects such as ants — which form a superorganism of unconditionally cooperative individuals and thus represent a level of organization that is intermediate between a classical society of individuals and an organism of cells — can help to determine common principles of disease defence across levels of organization. article_processing_charge: No article_type: letter_note author: - first_name: Sylvia full_name: Cremer, Sylvia id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87 last_name: Cremer orcid: 0000-0002-2193-3868 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Cremer S, Sixt MK. Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. 2022;22(12):713-714. doi:10.1038/s41577-022-00797-y apa: Cremer, S., & Sixt, M. K. (2022). Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. Springer Nature. https://doi.org/10.1038/s41577-022-00797-y chicago: Cremer, Sylvia, and Michael K Sixt. “Principles of Disease Defence in Organisms, Superorganisms and Societies.” Nature Reviews Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41577-022-00797-y. ieee: S. Cremer and M. K. Sixt, “Principles of disease defence in organisms, superorganisms and societies,” Nature Reviews Immunology, vol. 22, no. 12. Springer Nature, pp. 713–714, 2022. ista: Cremer S, Sixt MK. 2022. Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. 22(12), 713–714. mla: Cremer, Sylvia, and Michael K. Sixt. “Principles of Disease Defence in Organisms, Superorganisms and Societies.” Nature Reviews Immunology, vol. 22, no. 12, Springer Nature, 2022, pp. 713–14, doi:10.1038/s41577-022-00797-y. short: S. Cremer, M.K. Sixt, Nature Reviews Immunology 22 (2022) 713–714. date_created: 2023-01-12T12:03:14Z date_published: 2022-12-01T00:00:00Z date_updated: 2023-08-04T08:53:32Z day: '01' department: - _id: SyCr - _id: MiSi doi: 10.1038/s41577-022-00797-y external_id: isi: - '000871836300001' pmid: - '36284178' intvolume: ' 22' isi: 1 issue: '12' keyword: - Energy Engineering and Power Technology - Fuel Technology language: - iso: eng month: '12' oa_version: None page: 713-714 pmid: 1 publication: Nature Reviews Immunology publication_identifier: eissn: - 1474-1741 issn: - 1474-1733 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Principles of disease defence in organisms, superorganisms and societies type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 22 year: '2022' ... --- _id: '12272' abstract: - lang: eng text: Reading, interpreting and crawling along gradients of chemotactic cues is one of the most complex questions in cell biology. In this issue, Georgantzoglou et al. (2022. J. Cell. Biol.https://doi.org/10.1083/jcb.202103207) use in vivo models to map the temporal sequence of how neutrophils respond to an acutely arising gradient of chemoattractant. article_number: e202206127 article_processing_charge: No article_type: original author: - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: 'Stopp JA, Sixt MK. Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. 2022;221(8). doi:10.1083/jcb.202206127' apa: 'Stopp, J. A., & Sixt, M. K. (2022). Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202206127' chicago: 'Stopp, Julian A, and Michael K Sixt. “Plan Your Trip before You Leave: The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology. Rockefeller University Press, 2022. https://doi.org/10.1083/jcb.202206127.' ieee: 'J. A. Stopp and M. K. Sixt, “Plan your trip before you leave: The neutrophils’ search-and-run journey,” Journal of Cell Biology, vol. 221, no. 8. Rockefeller University Press, 2022.' ista: 'Stopp JA, Sixt MK. 2022. Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. 221(8), e202206127.' mla: 'Stopp, Julian A., and Michael K. Sixt. “Plan Your Trip before You Leave: The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology, vol. 221, no. 8, e202206127, Rockefeller University Press, 2022, doi:10.1083/jcb.202206127.' short: J.A. Stopp, M.K. Sixt, Journal of Cell Biology 221 (2022). date_created: 2023-01-16T10:01:08Z date_published: 2022-07-20T00:00:00Z date_updated: 2023-12-21T14:30:01Z day: '20' ddc: - '570' department: - _id: MiSi doi: 10.1083/jcb.202206127 external_id: isi: - '000874717200001' pmid: - '35856919' file: - access_level: open_access checksum: 6b1620743669679b48b9389bb40f5a11 content_type: application/pdf creator: dernst date_created: 2023-01-30T10:39:34Z date_updated: 2023-01-30T10:39:34Z file_id: '12451' file_name: 2022_JourCellBiology_Stopp.pdf file_size: 969969 relation: main_file success: 1 file_date_updated: 2023-01-30T10:39:34Z has_accepted_license: '1' intvolume: ' 221' isi: 1 issue: '8' keyword: - Cell Biology language: - iso: eng license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '07' oa: 1 oa_version: Published Version pmid: 1 publication: Journal of Cell Biology publication_identifier: eissn: - 1540-8140 issn: - 0021-9525 publication_status: published publisher: Rockefeller University Press quality_controlled: '1' related_material: record: - id: '14697' relation: dissertation_contains status: public scopus_import: '1' status: public title: 'Plan your trip before you leave: The neutrophils’ search-and-run journey' tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 221 year: '2022' ... --- _id: '10703' abstract: - lang: eng text: 'When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.' acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: EM-Fac acknowledgement: We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687. article_processing_charge: No article_type: original author: - first_name: Florian full_name: Gaertner, Florian last_name: Gaertner - first_name: Patricia full_name: Reis-Rodrigues, Patricia last_name: Reis-Rodrigues - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Juan full_name: Aguilera, Juan last_name: Aguilera - first_name: Michael full_name: Riedl, Michael id: 3BE60946-F248-11E8-B48F-1D18A9856A87 last_name: Riedl orcid: 0000-0003-4844-6311 - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner orcid: 0000-0002-1073-744X - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Vanessa full_name: Zheden, Vanessa id: 39C5A68A-F248-11E8-B48F-1D18A9856A87 last_name: Zheden orcid: 0000-0002-9438-4783 - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024 apa: Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. Cell Press ; Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024 chicago: Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024. ieee: F. Gaertner et al., “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” Developmental Cell, vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022. ista: Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9. mla: Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell, vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024. short: F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9. date_created: 2022-01-30T23:01:33Z date_published: 2022-01-10T00:00:00Z date_updated: 2024-03-27T23:30:23Z day: '10' ddc: - '570' department: - _id: MiSi - _id: EM-Fac - _id: NanoFab - _id: BjHo doi: 10.1016/j.devcel.2021.11.024 ec_funded: 1 external_id: isi: - '000768933800005' pmid: - '34919802' intvolume: ' 57' isi: 1 issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://www.sciencedirect.com/science/article/pii/S1534580721009497 month: '01' oa: 1 oa_version: Published Version page: 47-62.e9 pmid: 1 project: - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Cell Press ; Elsevier quality_controlled: '1' related_material: record: - id: '12726' relation: dissertation_contains status: public - id: '14530' relation: dissertation_contains status: public - id: '12401' relation: dissertation_contains status: public scopus_import: '1' status: public title: WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues tmp: image: /images/cc_by_nc_nd.png 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) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 57 year: '2022' ... --- _id: '12401' abstract: - lang: eng text: "Detachment of the cancer cells from the bulk of the tumor is the first step of metastasis, which\r\nis the primary cause of cancer related deaths. It is unclear, which factors contribute to this step.\r\nRecent studies indicate a crucial role of the tumor microenvironment in malignant\r\ntransformation and metastasis. Studying cancer cell invasion and detachments quantitatively in\r\nthe context of its physiological microenvironment is technically challenging. Especially, precise\r\ncontrol of microenvironmental properties in vivo is currently not possible. Here, I studied the\r\nrole of microenvironment geometry in the invasion and detachment of cancer cells from the\r\nbulk with a simplistic and reductionist approach. In this approach, I engineered microfluidic\r\ndevices to mimic a pseudo 3D extracellular matrix environment, where I was able to\r\nquantitatively tune the geometrical configuration of the microenvironment and follow tumor\r\ncells with fluorescence live imaging. To aid quantitative analysis I developed a widely applicable\r\nsoftware application to automatically analyze and visualize particle tracking data.\r\nQuantitative analysis of tumor cell invasion in isotropic and anisotropic microenvironments\r\nshowed that heterogeneity in the microenvironment promotes faster invasion and more\r\nfrequent detachment of cells. These observations correlated with overall higher speed of cells at\r\nthe edge of the bulk of the cells. In heterogeneous microenvironments cells preferentially\r\npassed through larger pores, thus invading areas of least resistance and generating finger-like\r\ninvasive structures. The detachments occurred mostly at the tips of these structures.\r\nTo investigate the potential mechanism, we established a two dimensional model to simulate\r\nactive Brownian particles representing the cell nuclei dynamics. These simulations backed our in\r\nvitro observations without the need of precise fitting the simulation parameters. Our model\r\nsuggests the importance of the pore heterogeneity in the direction perpendicular to the\r\norientation of bias field (lateral heterogeneity), which causes the interface roughening." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X citation: ama: Tasciyan S. Role of microenvironment heterogeneity in cancer cell invasion. 2022. doi:10.15479/at:ista:12401 apa: Tasciyan, S. (2022). Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12401 chicago: Tasciyan, Saren. “Role of Microenvironment Heterogeneity in Cancer Cell Invasion.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12401. ieee: S. Tasciyan, “Role of microenvironment heterogeneity in cancer cell invasion,” Institute of Science and Technology Austria, 2022. ista: Tasciyan S. 2022. Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria. mla: Tasciyan, Saren. Role of Microenvironment Heterogeneity in Cancer Cell Invasion. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12401. short: S. Tasciyan, Role of Microenvironment Heterogeneity in Cancer Cell Invasion, Institute of Science and Technology Austria, 2022. date_created: 2023-01-26T11:55:16Z date_published: 2022-12-22T00:00:00Z date_updated: 2023-12-21T23:30:04Z day: '22' ddc: - '610' degree_awarded: PhD department: - _id: GradSch - _id: MiSi doi: 10.15479/at:ista:12401 file: - access_level: open_access checksum: cc4a2b4a7e3c4ee8ef7f2dbf909b12bd content_type: application/pdf creator: cchlebak date_created: 2023-01-26T11:58:14Z date_updated: 2023-12-21T23:30:03Z embargo: 2023-12-20 file_id: '12402' file_name: PhD-Thesis_Saren Tasciyan_formatted_aftercrash_fixed_600dpi_95pc_final_PDFA3b.pdf file_size: 42059787 relation: main_file - access_level: closed checksum: f1b4ca98b8ab0cb043b1830971e9bd9c content_type: application/x-zip-compressed creator: cchlebak date_created: 2023-01-26T12:00:10Z date_updated: 2023-12-21T23:30:03Z embargo_to: open_access file_id: '12403' file_name: Source Files - Saren Tasciyan - PhD Thesis.zip file_size: 261256696 relation: source_file file_date_updated: 2023-12-21T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '105' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '679' relation: part_of_dissertation status: public - id: '10703' relation: part_of_dissertation status: public - id: '9429' relation: part_of_dissertation status: public - id: '7885' relation: part_of_dissertation status: public status: public supervisor: - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 title: Role of microenvironment heterogeneity in cancer cell invasion type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2022' ...