--- _id: '7623' abstract: - lang: eng text: A two-dimensional mathematical model for cells migrating without adhesion capabilities is presented and analyzed. Cells are represented by their cortex, which is modeled as an elastic curve, subject to an internal pressure force. Net polymerization or depolymerization in the cortex is modeled via local addition or removal of material, driving a cortical flow. The model takes the form of a fully nonlinear degenerate parabolic system. An existence analysis is carried out by adapting ideas from the theory of gradient flows. Numerical simulations show that these simple rules can account for the behavior observed in experiments, suggesting a possible mechanical mechanism for adhesion-independent motility. acknowledgement: This work has been supported by the Vienna Science and Technology Fund, Grant no. LS13-029. G.J. and C.S. also acknowledge support by the Austrian Science Fund, Grants no. W1245, F 65, and W1261, as well as by the Fondation Sciences Mathématiques de Paris, and by Paris-Sciences-et-Lettres. article_processing_charge: No article_type: original author: - first_name: Gaspard full_name: Jankowiak, Gaspard last_name: Jankowiak - first_name: Diane full_name: Peurichard, Diane last_name: Peurichard - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - first_name: Christian full_name: Schmeiser, Christian last_name: Schmeiser - 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: Jankowiak G, Peurichard D, Reversat A, Schmeiser C, Sixt MK. Modeling adhesion-independent cell migration. Mathematical Models and Methods in Applied Sciences. 2020;30(3):513-537. doi:10.1142/S021820252050013X apa: Jankowiak, G., Peurichard, D., Reversat, A., Schmeiser, C., & Sixt, M. K. (2020). Modeling adhesion-independent cell migration. Mathematical Models and Methods in Applied Sciences. World Scientific. https://doi.org/10.1142/S021820252050013X chicago: Jankowiak, Gaspard, Diane Peurichard, Anne Reversat, Christian Schmeiser, and Michael K Sixt. “Modeling Adhesion-Independent Cell Migration.” Mathematical Models and Methods in Applied Sciences. World Scientific, 2020. https://doi.org/10.1142/S021820252050013X. ieee: G. Jankowiak, D. Peurichard, A. Reversat, C. Schmeiser, and M. K. Sixt, “Modeling adhesion-independent cell migration,” Mathematical Models and Methods in Applied Sciences, vol. 30, no. 3. World Scientific, pp. 513–537, 2020. ista: Jankowiak G, Peurichard D, Reversat A, Schmeiser C, Sixt MK. 2020. Modeling adhesion-independent cell migration. Mathematical Models and Methods in Applied Sciences. 30(3), 513–537. mla: Jankowiak, Gaspard, et al. “Modeling Adhesion-Independent Cell Migration.” Mathematical Models and Methods in Applied Sciences, vol. 30, no. 3, World Scientific, 2020, pp. 513–37, doi:10.1142/S021820252050013X. short: G. Jankowiak, D. Peurichard, A. Reversat, C. Schmeiser, M.K. Sixt, Mathematical Models and Methods in Applied Sciences 30 (2020) 513–537. date_created: 2020-03-31T11:25:05Z date_published: 2020-03-18T00:00:00Z date_updated: 2023-08-18T10:18:56Z day: '18' department: - _id: MiSi doi: 10.1142/S021820252050013X external_id: arxiv: - '1903.09426' isi: - '000525349900003' intvolume: ' 30' isi: 1 issue: '3' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1903.09426 month: '03' oa: 1 oa_version: Preprint page: 513-537 project: - _id: 25AD6156-B435-11E9-9278-68D0E5697425 grant_number: LS13-029 name: Modeling of Polarization and Motility of Leukocytes in Three-Dimensional Environments publication: Mathematical Models and Methods in Applied Sciences publication_identifier: issn: - '02182025' publication_status: published publisher: World Scientific quality_controlled: '1' scopus_import: '1' status: public title: Modeling adhesion-independent cell migration type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 30 year: '2020' ... --- _id: '7885' abstract: - lang: eng text: Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: M-Shop acknowledgement: We thank A. Leithner and J. Renkawitz for discussion and critical reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic setups; the Bioimaging Facility of IST Austria for excellent support, as well as the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan, L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme. This work was supported by the European Research Council (ERC StG 281556 and CoG 724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476). F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687. article_processing_charge: No article_type: original author: - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - 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: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Juan L full_name: Aguilera Servin, Juan L id: 2A67C376-F248-11E8-B48F-1D18A9856A87 last_name: Aguilera Servin orcid: 0000-0002-2862-8372 - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Matthieu full_name: Piel, Matthieu last_name: Piel - first_name: Andrew full_name: Callan-Jones, Andrew last_name: Callan-Jones - first_name: Raphael full_name: Voituriez, Raphael last_name: Voituriez - 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: Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental topography. Nature. 2020;582:582–585. doi:10.1038/s41586-020-2283-z apa: Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography. Nature. Springer Nature. https://doi.org/10.1038/s41586-020-2283-z chicago: Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan, Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental Topography.” Nature. Springer Nature, 2020. https://doi.org/10.1038/s41586-020-2283-z. ieee: A. Reversat et al., “Cellular locomotion using environmental topography,” Nature, vol. 582. Springer Nature, pp. 582–585, 2020. ista: Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL, de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK. 2020. Cellular locomotion using environmental topography. Nature. 582, 582–585. mla: Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.” Nature, vol. 582, Springer Nature, 2020, pp. 582–585, doi:10.1038/s41586-020-2283-z. short: A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez, M.K. Sixt, Nature 582 (2020) 582–585. date_created: 2020-05-24T22:01:01Z date_published: 2020-06-25T00:00:00Z date_updated: 2024-03-28T23:30:24Z day: '25' department: - _id: NanoFab - _id: Bio - _id: MiSi doi: 10.1038/s41586-020-2283-z ec_funded: 1 external_id: isi: - '000532688300008' intvolume: ' 582' isi: 1 language: - iso: eng month: '06' oa_version: None page: 582–585 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes - _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 - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells publication: Nature publication_identifier: eissn: - '14764687' issn: - '00280836' publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/ record: - id: '14697' relation: dissertation_contains status: public - id: '12401' relation: dissertation_contains status: public scopus_import: '1' status: public title: Cellular locomotion using environmental topography type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 582 year: '2020' ... --- _id: '5672' abstract: - lang: eng text: The release of IgM is the first line of an antibody response and precedes the generation of high affinity IgG in germinal centers. Once secreted by freshly activated plasmablasts, IgM is released into the efferent lymph of reactive lymph nodes as early as 3 d after immunization. As pentameric IgM has an enormous size of 1,000 kD, its diffusibility is low, and one might wonder how it can pass through the densely lymphocyte-packed environment of a lymph node parenchyma in order to reach its exit. In this issue of JEM, Thierry et al. show that, in order to reach the blood stream, IgM molecules take a specific micro-anatomical route via lymph node conduits. article_processing_charge: No author: - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - 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: Reversat A, Sixt MK. IgM’s exit route. Journal of Experimental Medicine. 2018;215(12):2959-2961. doi:10.1084/jem.20181934 apa: Reversat, A., & Sixt, M. K. (2018). IgM’s exit route. Journal of Experimental Medicine. Rockefeller University Press. https://doi.org/10.1084/jem.20181934 chicago: Reversat, Anne, and Michael K Sixt. “IgM’s Exit Route.” Journal of Experimental Medicine. Rockefeller University Press, 2018. https://doi.org/10.1084/jem.20181934. ieee: A. Reversat and M. K. Sixt, “IgM’s exit route,” Journal of Experimental Medicine, vol. 215, no. 12. Rockefeller University Press, pp. 2959–2961, 2018. ista: Reversat A, Sixt MK. 2018. IgM’s exit route. Journal of Experimental Medicine. 215(12), 2959–2961. mla: Reversat, Anne, and Michael K. Sixt. “IgM’s Exit Route.” Journal of Experimental Medicine, vol. 215, no. 12, Rockefeller University Press, 2018, pp. 2959–61, doi:10.1084/jem.20181934. short: A. Reversat, M.K. Sixt, Journal of Experimental Medicine 215 (2018) 2959–2961. date_created: 2018-12-16T22:59:18Z date_published: 2018-11-20T00:00:00Z date_updated: 2023-09-11T14:12:06Z day: '20' ddc: - '570' department: - _id: MiSi doi: 10.1084/jem.20181934 external_id: isi: - '000451920600002' file: - access_level: open_access checksum: 687beea1d64c213f4cb9e3c29ec11a14 content_type: application/pdf creator: dernst date_created: 2019-02-06T08:49:52Z date_updated: 2020-07-14T12:47:09Z file_id: '5931' file_name: 2018_JournalExperMed_Reversat.pdf file_size: 1216437 relation: main_file file_date_updated: 2020-07-14T12:47:09Z has_accepted_license: '1' intvolume: ' 215' isi: 1 issue: '12' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '11' oa: 1 oa_version: Published Version page: 2959-2961 publication: Journal of Experimental Medicine publication_identifier: issn: - '00221007' publication_status: published publisher: Rockefeller University Press quality_controlled: '1' scopus_import: '1' status: public title: IgM's exit route 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 215 year: '2018' ... --- _id: '153' abstract: - lang: eng text: Cells migrating in multicellular organisms steadily traverse complex three-dimensional (3D) environments. To decipher the underlying cell biology, current experimental setups either use simplified 2D, tissue-mimetic 3D (e.g., collagen matrices) or in vivo environments. While only in vivo experiments are truly physiological, they do not allow for precise manipulation of environmental parameters. 2D in vitro experiments do allow mechanical and chemical manipulations, but increasing evidence demonstrates substantial differences of migratory mechanisms in 2D and 3D. Here, we describe simple, robust, and versatile “pillar forests” to investigate cell migration in complex but fully controllable 3D environments. Pillar forests are polydimethylsiloxane-based setups, in which two closely adjacent surfaces are interconnected by arrays of micrometer-sized pillars. Changing the pillar shape, size, height and the inter-pillar distance precisely manipulates microenvironmental parameters (e.g., pore sizes, micro-geometry, micro-topology), while being easily combined with chemotactic cues, surface coatings, diverse cell types and advanced imaging techniques. Thus, pillar forests combine the advantages of 2D cell migration assays with the precise definition of 3D environmental parameters. article_processing_charge: No author: - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - 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: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - 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: 'Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: Methods in Cell Biology. Vol 147. Academic Press; 2018:79-91. doi:10.1016/bs.mcb.2018.07.004' apa: Renkawitz, J., Reversat, A., Leithner, A. F., Merrin, J., & Sixt, M. K. (2018). Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In Methods in Cell Biology (Vol. 147, pp. 79–91). Academic Press. https://doi.org/10.1016/bs.mcb.2018.07.004 chicago: Renkawitz, Jörg, Anne Reversat, Alexander F Leithner, Jack Merrin, and Michael K Sixt. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” In Methods in Cell Biology, 147:79–91. Academic Press, 2018. https://doi.org/10.1016/bs.mcb.2018.07.004. ieee: J. Renkawitz, A. Reversat, A. F. Leithner, J. Merrin, and M. K. Sixt, “Micro-engineered ‘pillar forests’ to study cell migration in complex but controlled 3D environments,” in Methods in Cell Biology, vol. 147, Academic Press, 2018, pp. 79–91. ista: 'Renkawitz J, Reversat A, Leithner AF, Merrin J, Sixt MK. 2018.Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments. In: Methods in Cell Biology. vol. 147, 79–91.' mla: Renkawitz, Jörg, et al. “Micro-Engineered ‘Pillar Forests’ to Study Cell Migration in Complex but Controlled 3D Environments.” Methods in Cell Biology, vol. 147, Academic Press, 2018, pp. 79–91, doi:10.1016/bs.mcb.2018.07.004. short: J. Renkawitz, A. Reversat, A.F. Leithner, J. Merrin, M.K. Sixt, in:, Methods in Cell Biology, Academic Press, 2018, pp. 79–91. date_created: 2018-12-11T11:44:54Z date_published: 2018-07-27T00:00:00Z date_updated: 2023-09-13T08:56:35Z day: '27' department: - _id: MiSi - _id: NanoFab doi: 10.1016/bs.mcb.2018.07.004 external_id: isi: - '000452412300006' pmid: - '30165964' intvolume: ' 147' isi: 1 language: - iso: eng month: '07' oa_version: None page: 79 - 91 pmid: 1 publication: Methods in Cell Biology publication_identifier: issn: - 0091679X publication_status: published publisher: Academic Press publist_id: '7768' quality_controlled: '1' scopus_import: '1' status: public title: Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments type: book_chapter user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 147 year: '2018' ... --- _id: '569' abstract: - lang: eng text: The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings. article_number: e30867 author: - first_name: Felix full_name: Spira, Felix last_name: Spira - first_name: Sara full_name: Cuylen Haering, Sara last_name: Cuylen Haering - first_name: Shalin full_name: Mehta, Shalin last_name: Mehta - first_name: Matthias full_name: Samwer, Matthias last_name: Samwer - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - first_name: Amitabh full_name: Verma, Amitabh last_name: Verma - first_name: Rudolf full_name: Oldenbourg, Rudolf last_name: Oldenbourg - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 - first_name: Daniel full_name: Gerlich, Daniel last_name: Gerlich citation: ama: Spira F, Cuylen Haering S, Mehta S, et al. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. eLife. 2017;6. doi:10.7554/eLife.30867 apa: Spira, F., Cuylen Haering, S., Mehta, S., Samwer, M., Reversat, A., Verma, A., … Gerlich, D. (2017). Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.30867 chicago: Spira, Felix, Sara Cuylen Haering, Shalin Mehta, Matthias Samwer, Anne Reversat, Amitabh Verma, Rudolf Oldenbourg, Michael K Sixt, and Daniel Gerlich. “Cytokinesis in Vertebrate Cells Initiates by Contraction of an Equatorial Actomyosin Network Composed of Randomly Oriented Filaments.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.30867. ieee: F. Spira et al., “Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Spira F, Cuylen Haering S, Mehta S, Samwer M, Reversat A, Verma A, Oldenbourg R, Sixt MK, Gerlich D. 2017. Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments. eLife. 6, e30867. mla: Spira, Felix, et al. “Cytokinesis in Vertebrate Cells Initiates by Contraction of an Equatorial Actomyosin Network Composed of Randomly Oriented Filaments.” ELife, vol. 6, e30867, eLife Sciences Publications, 2017, doi:10.7554/eLife.30867. short: F. Spira, S. Cuylen Haering, S. Mehta, M. Samwer, A. Reversat, A. Verma, R. Oldenbourg, M.K. Sixt, D. Gerlich, ELife 6 (2017). date_created: 2018-12-11T11:47:14Z date_published: 2017-11-06T00:00:00Z date_updated: 2023-02-23T12:30:29Z day: '06' ddc: - '570' department: - _id: MiSi doi: 10.7554/eLife.30867 file: - access_level: open_access checksum: ba09c1451153d39e4f4b7cee013e314c content_type: application/pdf creator: system date_created: 2018-12-12T10:10:40Z date_updated: 2020-07-14T12:47:10Z file_id: '4829' file_name: IST-2017-919-v1+1_elife-30867-figures-v1.pdf file_size: 9666973 relation: main_file - access_level: open_access checksum: 01eb51f1d6ad679947415a51c988e137 content_type: application/pdf creator: system date_created: 2018-12-12T10:10:41Z date_updated: 2020-07-14T12:47:10Z file_id: '4830' file_name: IST-2017-919-v1+2_elife-30867-v1.pdf file_size: 5951246 relation: main_file file_date_updated: 2020-07-14T12:47:10Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '11' oa: 1 oa_version: Published Version publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '7245' pubrep_id: '919' quality_controlled: '1' scopus_import: 1 status: public title: Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 6 year: '2017' ... --- _id: '674' abstract: - lang: eng text: Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo. author: - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Veronika full_name: Bierbaum, Veronika id: 3FD04378-F248-11E8-B48F-1D18A9856A87 last_name: Bierbaum - first_name: Kari full_name: Vaahtomeri, Kari id: 368EE576-F248-11E8-B48F-1D18A9856A87 last_name: Vaahtomeri orcid: 0000-0001-7829-3518 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Markus full_name: Brown, Markus id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87 last_name: Brown - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Teresa full_name: Tarrant, Teresa last_name: Tarrant - first_name: Tobias full_name: Bollenbach, Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X - 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: Schwarz J, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 2017;27(9):1314-1325. doi:10.1016/j.cub.2017.04.004 apa: Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., de Vries, I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2017.04.004 chicago: Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology. Cell Press, 2017. https://doi.org/10.1016/j.cub.2017.04.004. ieee: J. Schwarz et al., “Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6,” Current Biology, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017. ista: Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner AF, Reversat A, Merrin J, Tarrant T, Bollenbach MT, Sixt MK. 2017. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325. mla: Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:10.1016/j.cub.2017.04.004. short: J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. de Vries, A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, M.T. Bollenbach, M.K. Sixt, Current Biology 27 (2017) 1314–1325. date_created: 2018-12-11T11:47:51Z date_published: 2017-05-09T00:00:00Z date_updated: 2023-02-23T12:50:44Z day: '09' department: - _id: MiSi - _id: Bio - _id: NanoFab doi: 10.1016/j.cub.2017.04.004 ec_funded: 1 intvolume: ' 27' issue: '9' language: - iso: eng month: '05' oa_version: None page: 1314 - 1325 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 25A8E5EA-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Y 564-B12 name: Cytoskeletal force generation and transduction of leukocytes (FWF) publication: Current Biology publication_identifier: issn: - '09609822' publication_status: published publisher: Cell Press publist_id: '7050' quality_controlled: '1' scopus_import: 1 status: public title: Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6 type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 27 year: '2017' ... --- _id: '1321' abstract: - lang: eng text: Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion. acknowledged_ssus: - _id: SSU acknowledgement: "This work was supported by the German Research Foundation (DFG) Priority Program SP 1464 to T.E.B.S. and M.S., and European Research Council (ERC GA 281556) and Human Frontiers Program grants to M.S.\r\nService Units of IST Austria for excellent technical support." article_processing_charge: No article_type: original author: - 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: Alexander full_name: Eichner, Alexander id: 4DFA52AE-F248-11E8-B48F-1D18A9856A87 last_name: Eichner - first_name: Jan full_name: Müller, Jan id: AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D last_name: Müller - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - first_name: Markus full_name: Brown, Markus id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87 last_name: Brown - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: David full_name: De Gorter, David last_name: De Gorter - first_name: Florian full_name: Schur, Florian id: 48AD8942-F248-11E8-B48F-1D18A9856A87 last_name: Schur orcid: 0000-0003-4790-8078 - first_name: Jonathan full_name: Bayerl, Jonathan last_name: Bayerl - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Stefan full_name: Wieser, Stefan id: 355AA5A0-F248-11E8-B48F-1D18A9856A87 last_name: Wieser orcid: 0000-0002-2670-2217 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Frank full_name: Lai, Frank last_name: Lai - first_name: Markus full_name: Moser, Markus last_name: Moser - first_name: Dontscho full_name: Kerjaschki, Dontscho last_name: Kerjaschki - first_name: Klemens full_name: Rottner, Klemens last_name: Rottner - first_name: Victor full_name: Small, Victor last_name: Small - first_name: Theresia full_name: Stradal, Theresia last_name: Stradal - 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: Leithner AF, Eichner A, Müller J, et al. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. 2016;18:1253-1259. doi:10.1038/ncb3426 apa: Leithner, A. F., Eichner, A., Müller, J., Reversat, A., Brown, M., Schwarz, J., … Sixt, M. K. (2016). Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. Nature Publishing Group. https://doi.org/10.1038/ncb3426 chicago: Leithner, Alexander F, Alexander Eichner, Jan Müller, Anne Reversat, Markus Brown, Jan Schwarz, Jack Merrin, et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature Cell Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/ncb3426. ieee: A. F. Leithner et al., “Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes,” Nature Cell Biology, vol. 18. Nature Publishing Group, pp. 1253–1259, 2016. ista: Leithner AF, Eichner A, Müller J, Reversat A, Brown M, Schwarz J, Merrin J, De Gorter D, Schur FK, Bayerl J, de Vries I, Wieser S, Hauschild R, Lai F, Moser M, Kerjaschki D, Rottner K, Small V, Stradal T, Sixt MK. 2016. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nature Cell Biology. 18, 1253–1259. mla: Leithner, Alexander F., et al. “Diversified Actin Protrusions Promote Environmental Exploration but Are Dispensable for Locomotion of Leukocytes.” Nature Cell Biology, vol. 18, Nature Publishing Group, 2016, pp. 1253–59, doi:10.1038/ncb3426. short: A.F. Leithner, A. Eichner, J. Müller, A. Reversat, M. Brown, J. Schwarz, J. Merrin, D. De Gorter, F.K. Schur, J. Bayerl, I. de Vries, S. Wieser, R. Hauschild, F. Lai, M. Moser, D. Kerjaschki, K. Rottner, V. Small, T. Stradal, M.K. Sixt, Nature Cell Biology 18 (2016) 1253–1259. date_created: 2018-12-11T11:51:21Z date_published: 2016-10-24T00:00:00Z date_updated: 2024-03-28T23:30:16Z day: '24' ddc: - '570' department: - _id: MiSi - _id: NanoFab - _id: Bio doi: 10.1038/ncb3426 ec_funded: 1 file: - access_level: open_access checksum: e1411cb7c99a2d9089c178a6abef25e7 content_type: application/pdf creator: dernst date_created: 2020-05-14T16:33:46Z date_updated: 2020-07-14T12:44:43Z file_id: '7844' file_name: 2018_NatureCell_Leithner.pdf file_size: 4433280 relation: main_file file_date_updated: 2020-07-14T12:44:43Z has_accepted_license: '1' intvolume: ' 18' language: - iso: eng month: '10' oa: 1 oa_version: Submitted Version page: 1253 - 1259 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) publication: Nature Cell Biology publication_status: published publisher: Nature Publishing Group publist_id: '5949' quality_controlled: '1' related_material: record: - id: '323' relation: dissertation_contains status: public scopus_import: 1 status: public title: Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes 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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 18 year: '2016' ...