--- _id: '14848' abstract: - lang: eng text: Regulating protein states is considered the core function of chaperones. However, despite their importance to all major cellular processes, the conformational changes that chaperones impart on polypeptide chains are difficult to study directly due to their heterogeneous, dynamic, and multi-step nature. Here, we review recent advances towards this aim using single-molecule manipulation methods, which are rapidly revealing new mechanisms of conformational control and helping to define a different perspective on the chaperone function. alternative_title: - New Developments in NMR article_processing_charge: No author: - first_name: F. full_name: Wruck, F. last_name: Wruck - first_name: Mario full_name: Avellaneda Sarrió, Mario id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E last_name: Avellaneda Sarrió orcid: 0000-0001-6406-524X - first_name: M. M. full_name: Naqvi, M. M. last_name: Naqvi - first_name: E. J. full_name: Koers, E. J. last_name: Koers - first_name: K. full_name: Till, K. last_name: Till - first_name: L. full_name: Gross, L. last_name: Gross - first_name: F. full_name: Moayed, F. last_name: Moayed - first_name: A. full_name: Roland, A. last_name: Roland - first_name: L. W. H. J. full_name: Heling, L. W. H. J. last_name: Heling - first_name: A. full_name: Mashaghi, A. last_name: Mashaghi - first_name: S. J. full_name: Tans, S. J. last_name: Tans citation: ama: 'Wruck F, Avellaneda Sarrió M, Naqvi MM, et al. Probing Single Chaperone Substrates. In: Hiller S, Liu M, He L, eds. Biophysics of Molecular Chaperones. Vol 29. Royal Society of Chemistry; 2023:278-318. doi:10.1039/bk9781839165986-00278' apa: Wruck, F., Avellaneda Sarrió, M., Naqvi, M. M., Koers, E. J., Till, K., Gross, L., … Tans, S. J. (2023). Probing Single Chaperone Substrates. In S. Hiller, M. Liu, & L. He (Eds.), Biophysics of Molecular Chaperones (Vol. 29, pp. 278–318). Royal Society of Chemistry. https://doi.org/10.1039/bk9781839165986-00278 chicago: Wruck, F., Mario Avellaneda Sarrió, M. M. Naqvi, E. J. Koers, K. Till, L. Gross, F. Moayed, et al. “Probing Single Chaperone Substrates.” In Biophysics of Molecular Chaperones, edited by Sebastian Hiller, Maili Liu, and Lichun He, 29:278–318. Royal Society of Chemistry, 2023. https://doi.org/10.1039/bk9781839165986-00278. ieee: F. Wruck et al., “Probing Single Chaperone Substrates,” in Biophysics of Molecular Chaperones, vol. 29, S. Hiller, M. Liu, and L. He, Eds. Royal Society of Chemistry, 2023, pp. 278–318. ista: 'Wruck F, Avellaneda Sarrió M, Naqvi MM, Koers EJ, Till K, Gross L, Moayed F, Roland A, Heling LWHJ, Mashaghi A, Tans SJ. 2023.Probing Single Chaperone Substrates. In: Biophysics of Molecular Chaperones. New Developments in NMR, vol. 29, 278–318.' mla: Wruck, F., et al. “Probing Single Chaperone Substrates.” Biophysics of Molecular Chaperones, edited by Sebastian Hiller et al., vol. 29, Royal Society of Chemistry, 2023, pp. 278–318, doi:10.1039/bk9781839165986-00278. short: F. Wruck, M. Avellaneda Sarrió, M.M. Naqvi, E.J. Koers, K. Till, L. Gross, F. Moayed, A. Roland, L.W.H.J. Heling, A. Mashaghi, S.J. Tans, in:, S. Hiller, M. Liu, L. He (Eds.), Biophysics of Molecular Chaperones, Royal Society of Chemistry, 2023, pp. 278–318. date_created: 2024-01-22T08:07:02Z date_published: 2023-11-01T00:00:00Z date_updated: 2024-01-23T12:01:53Z day: '01' department: - _id: MiSi doi: 10.1039/bk9781839165986-00278 editor: - first_name: Sebastian full_name: Hiller, Sebastian last_name: Hiller - first_name: Maili full_name: Liu, Maili last_name: Liu - first_name: Lichun full_name: He, Lichun last_name: He intvolume: ' 29' language: - iso: eng month: '11' oa_version: None page: 278-318 publication: Biophysics of Molecular Chaperones publication_identifier: eisbn: - '9781839165993' isbn: - '9781839162824' publication_status: published publisher: Royal Society of Chemistry quality_controlled: '1' status: public title: Probing Single Chaperone Substrates type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 29 year: '2023' ... --- _id: '9794' abstract: - lang: eng text: 'Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion.' acknowledged_ssus: - _id: Bio - _id: EM-Fac - _id: PreCl - _id: LifeSc acknowledgement: This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013. article_processing_charge: No article_type: original author: - first_name: Frank P full_name: Assen, Frank P id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87 last_name: Assen orcid: 0000-0003-3470-6119 - first_name: Jun full_name: Abe, Jun last_name: Abe - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Tommaso full_name: Costanzo, Tommaso id: D93824F4-D9BA-11E9-BB12-F207E6697425 last_name: Costanzo orcid: 0000-0001-9732-3815 - first_name: Gabriel full_name: Krens, Gabriel id: 2B819732-F248-11E8-B48F-1D18A9856A87 last_name: Krens orcid: 0000-0003-4761-5996 - first_name: Markus full_name: Brown, Markus id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87 last_name: Brown - first_name: Burkhard full_name: Ludewig, Burkhard last_name: Ludewig - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - first_name: Wolfgang full_name: Weninger, Wolfgang last_name: Weninger - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Sanjiv A. full_name: Luther, Sanjiv A. last_name: Luther - first_name: Jens V. full_name: Stein, Jens V. last_name: Stein - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-4561-241X citation: ama: Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4 apa: Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4 chicago: Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41590-022-01257-4. ieee: F. P. Assen et al., “Multitier mechanics control stromal adaptations in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature, pp. 1246–1255, 2022. ista: Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255. mla: Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:10.1038/s41590-022-01257-4. short: F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255. date_created: 2021-08-06T09:09:11Z date_published: 2022-07-11T00:00:00Z date_updated: 2023-08-02T06:53:07Z day: '11' ddc: - '570' department: - _id: SiHi - _id: CaHe - _id: EdHa - _id: EM-Fac - _id: Bio - _id: MiSi doi: 10.1038/s41590-022-01257-4 ec_funded: 1 external_id: isi: - '000822975900002' file: - access_level: open_access checksum: 628e7b49809f22c75b428842efe70c68 content_type: application/pdf creator: dernst date_created: 2022-07-25T07:11:32Z date_updated: 2022-07-25T07:11:32Z file_id: '11642' file_name: 2022_NatureImmunology_Assen.pdf file_size: 11475325 relation: main_file success: 1 file_date_updated: 2022-07-25T07:11:32Z has_accepted_license: '1' intvolume: ' 23' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1246-1255 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: Nature Immunology publication_identifier: eissn: - 1529-2916 issn: - 1529-2908 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Multitier mechanics control stromal adaptations in swelling lymph nodes tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 23 year: '2022' ... --- _id: '11588' abstract: - lang: eng text: Visualizing cell behavior and effector function on a single cell level has been crucial for understanding key aspects of mammalian biology. Due to their small size, large number and rapid recruitment into thrombi, there is a lack of data on fate and behavior of individual platelets in thrombosis and hemostasis. Here we report the use of platelet lineage restricted multi-color reporter mouse strains to delineate platelet function on a single cell level. We show that genetic labeling allows for single platelet and megakaryocyte (MK) tracking and morphological analysis in vivo and in vitro, while not affecting lineage functions. Using Cre-driven Confetti expression, we provide insights into temporal gene expression patterns as well as spatial clustering of MK in the bone marrow. In the vasculature, shape analysis of activated platelets recruited to thrombi identifies ubiquitous filopodia formation with no evidence of lamellipodia formation. Single cell tracking in complex thrombi reveals prominent myosin-dependent motility of platelets and highlights thrombus formation as a highly dynamic process amenable to modification and intervention of the acto-myosin cytoskeleton. Platelet function assays combining flow cytrometry, as well as in vivo, ex vivo and in vitro imaging show unaltered platelet functions of multicolor reporter mice compared to wild-type controls. In conclusion, platelet lineage multicolor reporter mice prove useful in furthering our understanding of platelet and MK biology on a single cell level. acknowledgement: "This study was supported by the Deutsche Forschungsgemeinschaft (DFG) SFB 914 ( to SM [B02 and Z01]), the DFG SFB 1123 (to SM [B06]), the DFG FOR 2033 (to SM), the German\r\nCenter for Cardiovascular Research (DZHK) (Clinician Scientist Programme), MHA 1.4VD (to SM), Postdoc Start-up Grant, 81X3600213 (to FG), 81X3600222 (to LN), the FP7 program\r\n(project 260309, PRESTIGE [to SM]). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 83344, ERC-2018-ADG “IMMUNOTHROMBOSIS” [to SM] and the Marie Skłodowska Curie Individual Fellowship (EU project 747687, LamelliActin [to FG]). " article_processing_charge: No article_type: original author: - first_name: Leo full_name: Nicolai, Leo last_name: Nicolai - first_name: Rainer full_name: Kaiser, Rainer last_name: Kaiser - first_name: Raphael full_name: Escaig, Raphael last_name: Escaig - first_name: Marie Louise full_name: Hoffknecht, Marie Louise last_name: Hoffknecht - first_name: Afra full_name: Anjum, Afra last_name: Anjum - first_name: Alexander full_name: Leunig, Alexander last_name: Leunig - first_name: Joachim full_name: Pircher, Joachim last_name: Pircher - first_name: Andreas full_name: Ehrlich, Andreas last_name: Ehrlich - first_name: Michael full_name: Lorenz, Michael last_name: Lorenz - first_name: Hellen full_name: Ishikawa-Ankerhold, Hellen last_name: Ishikawa-Ankerhold - first_name: William C. full_name: Aird, William C. last_name: Aird - first_name: Steffen full_name: Massberg, Steffen last_name: Massberg - first_name: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 citation: ama: Nicolai L, Kaiser R, Escaig R, et al. Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo. Haematologica. 2022;107(7):1669-1680. doi:10.3324/haematol.2021.278896 apa: Nicolai, L., Kaiser, R., Escaig, R., Hoffknecht, M. L., Anjum, A., Leunig, A., … Gärtner, F. R. (2022). Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo. Haematologica. Ferrata Storti Foundation. https://doi.org/10.3324/haematol.2021.278896 chicago: Nicolai, Leo, Rainer Kaiser, Raphael Escaig, Marie Louise Hoffknecht, Afra Anjum, Alexander Leunig, Joachim Pircher, et al. “Single Platelet and Megakaryocyte Morpho-Dynamics Uncovered by Multicolor Reporter Mouse Strains in Vitro and in Vivo.” Haematologica. Ferrata Storti Foundation, 2022. https://doi.org/10.3324/haematol.2021.278896. ieee: L. Nicolai et al., “Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo,” Haematologica, vol. 107, no. 7. Ferrata Storti Foundation, pp. 1669–1680, 2022. ista: Nicolai L, Kaiser R, Escaig R, Hoffknecht ML, Anjum A, Leunig A, Pircher J, Ehrlich A, Lorenz M, Ishikawa-Ankerhold H, Aird WC, Massberg S, Gärtner FR. 2022. Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo. Haematologica. 107(7), 1669–1680. mla: Nicolai, Leo, et al. “Single Platelet and Megakaryocyte Morpho-Dynamics Uncovered by Multicolor Reporter Mouse Strains in Vitro and in Vivo.” Haematologica, vol. 107, no. 7, Ferrata Storti Foundation, 2022, pp. 1669–80, doi:10.3324/haematol.2021.278896. short: L. Nicolai, R. Kaiser, R. Escaig, M.L. Hoffknecht, A. Anjum, A. Leunig, J. Pircher, A. Ehrlich, M. Lorenz, H. Ishikawa-Ankerhold, W.C. Aird, S. Massberg, F.R. Gärtner, Haematologica 107 (2022) 1669–1680. date_created: 2022-07-17T22:01:54Z date_published: 2022-07-01T00:00:00Z date_updated: 2023-08-03T12:01:01Z day: '01' ddc: - '570' department: - _id: MiSi doi: 10.3324/haematol.2021.278896 ec_funded: 1 external_id: isi: - '000823746100018' file: - access_level: open_access checksum: 9b47830945f3c30428fe9cfee2dc4a8a content_type: application/pdf creator: dernst date_created: 2022-07-18T07:51:55Z date_updated: 2022-07-18T07:51:55Z file_id: '11595' file_name: 2022_Haematologica_Nicolai.pdf file_size: 1722094 relation: main_file success: 1 file_date_updated: 2022-07-18T07:51:55Z has_accepted_license: '1' intvolume: ' 107' isi: 1 issue: '7' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1669-1680 project: - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells publication: Haematologica publication_identifier: eissn: - 1592-8721 issn: - 0390-6078 publication_status: published publisher: Ferrata Storti Foundation quality_controlled: '1' scopus_import: '1' status: public title: Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 107 year: '2022' ... --- _id: '11843' abstract: - lang: eng text: A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease. acknowledged_ssus: - _id: Bio - _id: PreCl - _id: EM-Fac acknowledgement: We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS. article_number: e78995 article_processing_charge: Yes article_type: original author: - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner - first_name: Ivana full_name: Glatzová, Ivana id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d last_name: Glatzová - first_name: Michael S. full_name: Lukesch, Michael S. last_name: Lukesch - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - 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: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 2022;11. doi:10.7554/eLife.78995 apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., & Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.78995 chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/eLife.78995. ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” eLife, vol. 11. eLife Sciences Publications, 2022. ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995. mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife Sciences Publications, 2022, doi:10.7554/eLife.78995. short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022). date_created: 2022-08-14T22:01:46Z date_published: 2022-07-26T00:00:00Z date_updated: 2023-08-03T12:54:21Z day: '26' ddc: - '570' department: - _id: MiSi - _id: CaGu doi: 10.7554/eLife.78995 ec_funded: 1 external_id: isi: - '000838410200001' file: - access_level: open_access checksum: 002a3c7c7ea5caa9af9cfbea308f6ea4 content_type: application/pdf creator: cchlebak date_created: 2022-08-16T08:57:37Z date_updated: 2022-08-16T08:57:37Z file_id: '11861' file_name: 2022_eLife_Tomasek.pdf file_size: 2057577 relation: main_file success: 1 file_date_updated: 2022-08-16T08:57:37Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 26018E70-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29911 name: Mechanical adaptation of lamellipodial actin publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: record: - id: '10316' relation: earlier_version status: public scopus_import: '1' status: public title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14 tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2022' ... --- _id: '12085' abstract: - lang: eng text: Molecular catch bonds are ubiquitous in biology and essential for processes like leucocyte extravasion1 and cellular mechanosensing2. Unlike normal (slip) bonds, catch bonds strengthen under tension. The current paradigm is that this feature provides ‘strength on demand3’, thus enabling cells to increase rigidity under stress1,4,5,6. However, catch bonds are often weaker than slip bonds because they have cryptic binding sites that are usually buried7,8. Here we show that catch bonds render reconstituted cytoskeletal actin networks stronger than slip bonds, even though the individual bonds are weaker. Simulations show that slip bonds remain trapped in stress-free areas, whereas weak binding allows catch bonds to mitigate crack initiation by moving to high-tension areas. This ‘dissociation on demand’ explains how cells combine mechanical strength with the adaptability required for shape change, and is relevant to diseases where catch bonding is compromised7,9, including focal segmental glomerulosclerosis10 caused by the α-actinin-4 mutant studied here. We surmise that catch bonds are the key to create life-like materials. acknowledgement: 'We thank M. van Hecke and C. Alkemade for critical reading of the manuscript. We thank P. R. ten Wolde, K. Storm, W. Ellenbroek, C. Broedersz, D. Brueckner and M. Berger for fruitful discussions. We thank W. Brieher and V. Tang from the University of Illinois for the kind gift of purified α-actinin-4 (WT and the K255E point mutant) and their plasmids; M. Kuit-Vinkenoog and J. den Haan for actin and further purification of α-actinin-4; A. Goutou and I. Isturiz-Petitjean for co-sedimentation measurements and V. Sunderlíková for the design, mutagenesis, cloning and purifying of the α-actinin-4 constructs used in the single-molecule experiments. We gratefully acknowledge financial support from the following sources: research program of the Netherlands Organization for Scientific Research (NWO) (S.J.T., A.R. and M.J.A.); ERC Starting Grant (335672-MINICELL) (G.H.K. and Y.M.). ‘BaSyC—Building a Synthetic Cell’ Gravitation grant (024.003.019) of the Netherlands Ministry of Education, Culture and Science (OCW) and the Netherlands Organisation for Scientific Research (G.H.K. and L.B.); and support from the National Institutes of Health (1R01GM126256) (T.K. and W.J.).' article_processing_charge: No article_type: original author: - first_name: Yuval full_name: Mulla, Yuval last_name: Mulla - first_name: Mario full_name: Avellaneda Sarrió, Mario id: DC4BA84C-56E6-11EA-AD5D-348C3DDC885E last_name: Avellaneda Sarrió orcid: 0000-0001-6406-524X - first_name: Antoine full_name: Roland, Antoine last_name: Roland - first_name: Lucia full_name: Baldauf, Lucia last_name: Baldauf - first_name: Wonyeong full_name: Jung, Wonyeong last_name: Jung - first_name: Taeyoon full_name: Kim, Taeyoon last_name: Kim - first_name: Sander J. full_name: Tans, Sander J. last_name: Tans - first_name: Gijsje H. full_name: Koenderink, Gijsje H. last_name: Koenderink citation: ama: Mulla Y, Avellaneda Sarrió M, Roland A, et al. Weak catch bonds make strong networks. Nature Materials. 2022;21(9):1019-1023. doi:10.1038/s41563-022-01288-0 apa: Mulla, Y., Avellaneda Sarrió, M., Roland, A., Baldauf, L., Jung, W., Kim, T., … Koenderink, G. H. (2022). Weak catch bonds make strong networks. Nature Materials. Springer Nature. https://doi.org/10.1038/s41563-022-01288-0 chicago: Mulla, Yuval, Mario Avellaneda Sarrió, Antoine Roland, Lucia Baldauf, Wonyeong Jung, Taeyoon Kim, Sander J. Tans, and Gijsje H. Koenderink. “Weak Catch Bonds Make Strong Networks.” Nature Materials. Springer Nature, 2022. https://doi.org/10.1038/s41563-022-01288-0. ieee: Y. Mulla et al., “Weak catch bonds make strong networks,” Nature Materials, vol. 21, no. 9. Springer Nature, pp. 1019–1023, 2022. ista: Mulla Y, Avellaneda Sarrió M, Roland A, Baldauf L, Jung W, Kim T, Tans SJ, Koenderink GH. 2022. Weak catch bonds make strong networks. Nature Materials. 21(9), 1019–1023. mla: Mulla, Yuval, et al. “Weak Catch Bonds Make Strong Networks.” Nature Materials, vol. 21, no. 9, Springer Nature, 2022, pp. 1019–23, doi:10.1038/s41563-022-01288-0. short: Y. Mulla, M. Avellaneda Sarrió, A. Roland, L. Baldauf, W. Jung, T. Kim, S.J. Tans, G.H. Koenderink, Nature Materials 21 (2022) 1019–1023. date_created: 2022-09-11T22:01:57Z date_published: 2022-09-01T00:00:00Z date_updated: 2023-08-03T14:08:47Z day: '01' department: - _id: MiSi doi: 10.1038/s41563-022-01288-0 external_id: isi: - '000844592000002' pmid: - '36008604' intvolume: ' 21' isi: 1 issue: '9' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.07.27.219618 month: '09' oa: 1 oa_version: Preprint page: 1019-1023 pmid: 1 publication: Nature Materials publication_identifier: eissn: - 1476-4660 issn: - 1476-1122 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Weak catch bonds make strong networks type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 21 year: '2022' ... --- _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 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' ...