--- _id: '7009' abstract: - lang: eng text: Cell migration is essential for physiological processes as diverse as development, immune defence and wound healing. It is also a hallmark of cancer malignancy. Thousands of publications have elucidated detailed molecular and biophysical mechanisms of cultured cells migrating on flat, 2D substrates of glass and plastic. However, much less is known about how cells successfully navigate the complex 3D environments of living tissues. In these more complex, native environments, cells use multiple modes of migration, including mesenchymal, amoeboid, lobopodial and collective, and these are governed by the local extracellular microenvironment, specific modalities of Rho GTPase signalling and non- muscle myosin contractility. Migration through 3D environments is challenging because it requires the cell to squeeze through complex or dense extracellular structures. Doing so requires specific cellular adaptations to mechanical features of the extracellular matrix (ECM) or its remodelling. In addition, besides navigating through diverse ECM environments and overcoming extracellular barriers, cells often interact with neighbouring cells and tissues through physical and signalling interactions. Accordingly, cells need to call on an impressively wide diversity of mechanisms to meet these challenges. This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments. It focuses on principles rather than details of migratory mechanisms and draws comparisons between 1D, 2D and 3D migration. article_processing_charge: No article_type: review author: - first_name: KM full_name: Yamada, KM last_name: Yamada - 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: Yamada K, Sixt MK. Mechanisms of 3D cell migration. Nature Reviews Molecular Cell Biology. 2019;20(12):738–752. doi:10.1038/s41580-019-0172-9 apa: Yamada, K., & Sixt, M. K. (2019). Mechanisms of 3D cell migration. Nature Reviews Molecular Cell Biology. Springer Nature. https://doi.org/10.1038/s41580-019-0172-9 chicago: Yamada, KM, and Michael K Sixt. “Mechanisms of 3D Cell Migration.” Nature Reviews Molecular Cell Biology. Springer Nature, 2019. https://doi.org/10.1038/s41580-019-0172-9. ieee: K. Yamada and M. K. Sixt, “Mechanisms of 3D cell migration,” Nature Reviews Molecular Cell Biology, vol. 20, no. 12. Springer Nature, pp. 738–752, 2019. ista: Yamada K, Sixt MK. 2019. Mechanisms of 3D cell migration. Nature Reviews Molecular Cell Biology. 20(12), 738–752. mla: Yamada, KM, and Michael K. Sixt. “Mechanisms of 3D Cell Migration.” Nature Reviews Molecular Cell Biology, vol. 20, no. 12, Springer Nature, 2019, pp. 738–752, doi:10.1038/s41580-019-0172-9. short: K. Yamada, M.K. Sixt, Nature Reviews Molecular Cell Biology 20 (2019) 738–752. date_created: 2019-11-12T14:54:42Z date_published: 2019-12-01T00:00:00Z date_updated: 2023-08-30T07:22:20Z day: '01' department: - _id: MiSi doi: 10.1038/s41580-019-0172-9 external_id: isi: - '000497966900007' pmid: - '31582855' intvolume: ' 20' isi: 1 issue: '12' language: - iso: eng month: '12' oa_version: None page: 738–752 pmid: 1 publication: Nature Reviews Molecular Cell Biology publication_identifier: eissn: - 1471-0080 issn: - 1471-0072 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Mechanisms of 3D cell migration type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 20 year: '2019' ... --- _id: '6988' abstract: - lang: eng text: 'Platelets are central players in thrombosis and hemostasis but are increasingly recognized as key components of the immune system. They shape ensuing immune responses by recruiting leukocytes, and support the development of adaptive immunity. Recent data shed new light on the complex role of platelets in immunity. Here, we summarize experimental and clinical data on the role of platelets in host defense against bacteria. Platelets bind, contain, and kill bacteria directly; however, platelet proinflammatory effector functions and cross-talk with the coagulation system, can also result in damage to the host (e.g., acute lung injury and sepsis). Novel clinical insights support this dichotomy: platelet inhibition/thrombocytopenia can be either harmful or protective, depending on pathophysiological context. Clinical studies are currently addressing this aspect in greater depth.' article_processing_charge: No article_type: review author: - first_name: Leo full_name: Nicolai, Leo last_name: Nicolai - 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: Steffen full_name: Massberg, Steffen last_name: Massberg citation: ama: 'Nicolai L, Gärtner FR, Massberg S. Platelets in host defense: Experimental and clinical insights. Trends in Immunology. 2019;40(10):922-938. doi:10.1016/j.it.2019.08.004' apa: 'Nicolai, L., Gärtner, F. R., & Massberg, S. (2019). Platelets in host defense: Experimental and clinical insights. Trends in Immunology. Cell Press. https://doi.org/10.1016/j.it.2019.08.004' chicago: 'Nicolai, Leo, Florian R Gärtner, and Steffen Massberg. “Platelets in Host Defense: Experimental and Clinical Insights.” Trends in Immunology. Cell Press, 2019. https://doi.org/10.1016/j.it.2019.08.004.' ieee: 'L. Nicolai, F. R. Gärtner, and S. Massberg, “Platelets in host defense: Experimental and clinical insights,” Trends in Immunology, vol. 40, no. 10. Cell Press, pp. 922–938, 2019.' ista: 'Nicolai L, Gärtner FR, Massberg S. 2019. Platelets in host defense: Experimental and clinical insights. Trends in Immunology. 40(10), 922–938.' mla: 'Nicolai, Leo, et al. “Platelets in Host Defense: Experimental and Clinical Insights.” Trends in Immunology, vol. 40, no. 10, Cell Press, 2019, pp. 922–38, doi:10.1016/j.it.2019.08.004.' short: L. Nicolai, F.R. Gärtner, S. Massberg, Trends in Immunology 40 (2019) 922–938. date_created: 2019-11-04T16:27:36Z date_published: 2019-10-01T00:00:00Z date_updated: 2023-08-30T07:19:23Z day: '01' department: - _id: MiSi doi: 10.1016/j.it.2019.08.004 ec_funded: 1 external_id: isi: - '000493292100005' pmid: - '31601520' intvolume: ' 40' isi: 1 issue: '10' language: - iso: eng month: '10' oa_version: None page: 922-938 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: Trends in Immunology publication_identifier: issn: - 1471-4906 publication_status: published publisher: Cell Press quality_controlled: '1' scopus_import: '1' status: public title: 'Platelets in host defense: Experimental and clinical insights' type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 40 year: '2019' ... --- _id: '6979' article_processing_charge: No article_type: original author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - 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: 'Kopf A, Sixt MK. Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. Current Biology. 2019;29(20):R1091-R1093. doi:10.1016/j.cub.2019.08.068' apa: 'Kopf, A., & Sixt, M. K. (2019). Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2019.08.068' chicago: 'Kopf, Aglaja, and Michael K Sixt. “Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal.” Current Biology. Cell Press, 2019. https://doi.org/10.1016/j.cub.2019.08.068.' ieee: 'A. Kopf and M. K. Sixt, “Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal,” Current Biology, vol. 29, no. 20. Cell Press, pp. R1091–R1093, 2019.' ista: 'Kopf A, Sixt MK. 2019. Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. Current Biology. 29(20), R1091–R1093.' mla: 'Kopf, Aglaja, and Michael K. Sixt. “Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal.” Current Biology, vol. 29, no. 20, Cell Press, 2019, pp. R1091–93, doi:10.1016/j.cub.2019.08.068.' short: A. Kopf, M.K. Sixt, Current Biology 29 (2019) R1091–R1093. date_created: 2019-11-04T15:18:29Z date_published: 2019-10-21T00:00:00Z date_updated: 2023-09-05T12:43:43Z day: '21' department: - _id: MiSi doi: 10.1016/j.cub.2019.08.068 external_id: isi: - '000491286200016' pmid: - '31639357' intvolume: ' 29' isi: 1 issue: '20' language: - iso: eng month: '10' oa_version: None page: R1091-R1093 pmid: 1 publication: Current Biology publication_identifier: eissn: - 1879-0445 issn: - 0960-9822 publication_status: published publisher: Cell Press quality_controlled: '1' scopus_import: '1' status: public title: 'Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal' type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 29 year: '2019' ... --- _id: '7105' abstract: - lang: eng text: Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence. article_processing_charge: No article_type: original author: - first_name: Lawrence full_name: Yolland, Lawrence last_name: Yolland - first_name: Mubarik full_name: Burki, Mubarik last_name: Burki - first_name: Stefania full_name: Marcotti, Stefania last_name: Marcotti - first_name: Andrei full_name: Luchici, Andrei last_name: Luchici - first_name: Fiona N. full_name: Kenny, Fiona N. last_name: Kenny - first_name: John Robert full_name: Davis, John Robert last_name: Davis - first_name: Eduardo full_name: Serna-Morales, Eduardo last_name: Serna-Morales - first_name: Jan full_name: Müller, Jan id: AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D last_name: Müller - 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: Andrew full_name: Davidson, Andrew last_name: Davidson - first_name: Will full_name: Wood, Will last_name: Wood - first_name: Linus J. full_name: Schumacher, Linus J. last_name: Schumacher - first_name: Robert G. full_name: Endres, Robert G. last_name: Endres - first_name: Mark full_name: Miodownik, Mark last_name: Miodownik - first_name: Brian M. full_name: Stramer, Brian M. last_name: Stramer citation: ama: Yolland L, Burki M, Marcotti S, et al. Persistent and polarized global actin flow is essential for directionality during cell migration. Nature Cell Biology. 2019;21(11):1370-1381. doi:10.1038/s41556-019-0411-5 apa: Yolland, L., Burki, M., Marcotti, S., Luchici, A., Kenny, F. N., Davis, J. R., … Stramer, B. M. (2019). Persistent and polarized global actin flow is essential for directionality during cell migration. Nature Cell Biology. Springer Nature. https://doi.org/10.1038/s41556-019-0411-5 chicago: Yolland, Lawrence, Mubarik Burki, Stefania Marcotti, Andrei Luchici, Fiona N. Kenny, John Robert Davis, Eduardo Serna-Morales, et al. “Persistent and Polarized Global Actin Flow Is Essential for Directionality during Cell Migration.” Nature Cell Biology. Springer Nature, 2019. https://doi.org/10.1038/s41556-019-0411-5. ieee: L. Yolland et al., “Persistent and polarized global actin flow is essential for directionality during cell migration,” Nature Cell Biology, vol. 21, no. 11. Springer Nature, pp. 1370–1381, 2019. ista: Yolland L, Burki M, Marcotti S, Luchici A, Kenny FN, Davis JR, Serna-Morales E, Müller J, Sixt MK, Davidson A, Wood W, Schumacher LJ, Endres RG, Miodownik M, Stramer BM. 2019. Persistent and polarized global actin flow is essential for directionality during cell migration. Nature Cell Biology. 21(11), 1370–1381. mla: Yolland, Lawrence, et al. “Persistent and Polarized Global Actin Flow Is Essential for Directionality during Cell Migration.” Nature Cell Biology, vol. 21, no. 11, Springer Nature, 2019, pp. 1370–81, doi:10.1038/s41556-019-0411-5. short: L. Yolland, M. Burki, S. Marcotti, A. Luchici, F.N. Kenny, J.R. Davis, E. Serna-Morales, J. Müller, M.K. Sixt, A. Davidson, W. Wood, L.J. Schumacher, R.G. Endres, M. Miodownik, B.M. Stramer, Nature Cell Biology 21 (2019) 1370–1381. date_created: 2019-11-25T08:55:00Z date_published: 2019-11-01T00:00:00Z date_updated: 2023-09-06T11:08:52Z day: '01' department: - _id: MiSi doi: 10.1038/s41556-019-0411-5 external_id: isi: - '000495888300009' pmid: - '31685997' intvolume: ' 21' isi: 1 issue: '11' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025891 month: '11' oa: 1 oa_version: Submitted Version page: 1370-1381 pmid: 1 publication: Nature Cell Biology publication_identifier: eissn: - 1476-4679 issn: - 1465-7392 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Persistent and polarized global actin flow is essential for directionality during cell migration type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 21 year: '2019' ... --- _id: '7420' abstract: - lang: eng text: β1-integrins mediate cell–matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic. article_number: jcs233387 article_processing_charge: No article_type: original author: - first_name: Pranshu full_name: Sahgal, Pranshu last_name: Sahgal - first_name: Jonna H full_name: Alanko, Jonna H id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87 last_name: Alanko orcid: 0000-0002-7698-3061 - first_name: Jaroslav full_name: Icha, Jaroslav last_name: Icha - first_name: Ilkka full_name: Paatero, Ilkka last_name: Paatero - first_name: Hellyeh full_name: Hamidi, Hellyeh last_name: Hamidi - first_name: Antti full_name: Arjonen, Antti last_name: Arjonen - first_name: Mika full_name: Pietilä, Mika last_name: Pietilä - first_name: Anne full_name: Rokka, Anne last_name: Rokka - first_name: Johanna full_name: Ivaska, Johanna last_name: Ivaska citation: ama: Sahgal P, Alanko JH, Icha J, et al. GGA2 and RAB13 promote activity-dependent β1-integrin recycling. Journal of Cell Science. 2019;132(11). doi:10.1242/jcs.233387 apa: Sahgal, P., Alanko, J. H., Icha, J., Paatero, I., Hamidi, H., Arjonen, A., … Ivaska, J. (2019). GGA2 and RAB13 promote activity-dependent β1-integrin recycling. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.233387 chicago: Sahgal, Pranshu, Jonna H Alanko, Jaroslav Icha, Ilkka Paatero, Hellyeh Hamidi, Antti Arjonen, Mika Pietilä, Anne Rokka, and Johanna Ivaska. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” Journal of Cell Science. The Company of Biologists, 2019. https://doi.org/10.1242/jcs.233387. ieee: P. Sahgal et al., “GGA2 and RAB13 promote activity-dependent β1-integrin recycling,” Journal of Cell Science, vol. 132, no. 11. The Company of Biologists, 2019. ista: Sahgal P, Alanko JH, Icha J, Paatero I, Hamidi H, Arjonen A, Pietilä M, Rokka A, Ivaska J. 2019. GGA2 and RAB13 promote activity-dependent β1-integrin recycling. Journal of Cell Science. 132(11), jcs233387. mla: Sahgal, Pranshu, et al. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” Journal of Cell Science, vol. 132, no. 11, jcs233387, The Company of Biologists, 2019, doi:10.1242/jcs.233387. short: P. Sahgal, J.H. Alanko, J. Icha, I. Paatero, H. Hamidi, A. Arjonen, M. Pietilä, A. Rokka, J. Ivaska, Journal of Cell Science 132 (2019). date_created: 2020-01-30T10:31:42Z date_published: 2019-06-07T00:00:00Z date_updated: 2023-09-06T15:01:00Z day: '07' department: - _id: MiSi doi: 10.1242/jcs.233387 external_id: isi: - '000473327900017' pmid: - '31076515' intvolume: ' 132' isi: 1 issue: '11' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1242/jcs.233387 month: '06' oa: 1 oa_version: Published Version pmid: 1 publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' status: public title: GGA2 and RAB13 promote activity-dependent β1-integrin recycling type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 132 year: '2019' ... --- _id: '7404' abstract: - lang: eng text: The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation. article_number: dev171397 article_processing_charge: No article_type: original author: - first_name: Tomke full_name: Stürner, Tomke last_name: Stürner - first_name: Anastasia full_name: Tatarnikova, Anastasia last_name: Tatarnikova - first_name: Jan full_name: Müller, Jan id: AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D last_name: Müller - first_name: Barbara full_name: Schaffran, Barbara last_name: Schaffran - first_name: Hermann full_name: Cuntz, Hermann last_name: Cuntz - first_name: Yun full_name: Zhang, Yun last_name: Zhang - first_name: Maria full_name: Nemethova, Maria id: 34E27F1C-F248-11E8-B48F-1D18A9856A87 last_name: Nemethova - first_name: Sven full_name: Bogdan, Sven last_name: Bogdan - first_name: Vic full_name: Small, Vic last_name: Small - first_name: Gaia full_name: Tavosanis, Gaia last_name: Tavosanis citation: ama: Stürner T, Tatarnikova A, Müller J, et al. Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. Development. 2019;146(7). doi:10.1242/dev.171397 apa: Stürner, T., Tatarnikova, A., Müller, J., Schaffran, B., Cuntz, H., Zhang, Y., … Tavosanis, G. (2019). Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. Development. The Company of Biologists. https://doi.org/10.1242/dev.171397 chicago: Stürner, Tomke, Anastasia Tatarnikova, Jan Müller, Barbara Schaffran, Hermann Cuntz, Yun Zhang, Maria Nemethova, Sven Bogdan, Vic Small, and Gaia Tavosanis. “Transient Localization of the Arp2/3 Complex Initiates Neuronal Dendrite Branching in Vivo.” Development. The Company of Biologists, 2019. https://doi.org/10.1242/dev.171397. ieee: T. Stürner et al., “Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo,” Development, vol. 146, no. 7. The Company of Biologists, 2019. ista: Stürner T, Tatarnikova A, Müller J, Schaffran B, Cuntz H, Zhang Y, Nemethova M, Bogdan S, Small V, Tavosanis G. 2019. Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo. Development. 146(7), dev171397. mla: Stürner, Tomke, et al. “Transient Localization of the Arp2/3 Complex Initiates Neuronal Dendrite Branching in Vivo.” Development, vol. 146, no. 7, dev171397, The Company of Biologists, 2019, doi:10.1242/dev.171397. short: T. Stürner, A. Tatarnikova, J. Müller, B. Schaffran, H. Cuntz, Y. Zhang, M. Nemethova, S. Bogdan, V. Small, G. Tavosanis, Development 146 (2019). date_created: 2020-01-29T16:27:10Z date_published: 2019-04-04T00:00:00Z date_updated: 2023-09-07T14:47:00Z day: '04' department: - _id: MiSi doi: 10.1242/dev.171397 external_id: isi: - '000464583200006' pmid: - '30910826' intvolume: ' 146' isi: 1 issue: '7' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1242/dev.171397 month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: Development publication_identifier: eissn: - 1477-9129 issn: - 0950-1991 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 146 year: '2019' ... --- _id: '6947' abstract: - lang: eng text: Lymph nodes are es s ential organs of the immune s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular cells (FRCs) are the main stromal cells and form a sponge-like extracellular matrix network, called conduits , which they thems elves enwrap and contract. Lymph, containing s oluble antigens , arrive in lymph nodes via afferent lymphatic vessels that connect to the s ubcaps ular s inus and conduit network. According to the current paradigm, the conduit network dis tributes afferent lymph through lymph nodes and thus provides acces s for immune cells to lymph-borne antigens. An elas tic caps ule s urrounds the organ and confines the immune cells and FRC network. Lymph nodes are completely packed with lymphocytes and lymphocyte numbers directly dictates the size of the organ. Although lymphocytes cons tantly enter and leave the lymph node, its s ize remains remarkedly s table under homeostatic conditions. It is only partly known how the cellularity and s ize of the lymph node is regulated and how the lymph node is able to swell in inflammation. The role of the FRC network in lymph node s welling and trans fer of fluids are inves tigated in this thes is. Furthermore, we s tudied what trafficking routes are us ed by cancer cells in lymph nodes to form distal metastases.We examined the role of a mechanical feedback in regulation of lymph node swelling. Using parallel plate compression and UV-las er cutting experiments we dis s ected the mechanical force dynamics of the whole lymph node, and individually for FRCs and the caps ule. Physical forces generated by packed lymphocytes directly affect the tens ion on the FRC network and capsule, which increases its resistance to swelling. This implies a feedback mechanism between tis s ue pres s ure and ability of lymphocytes to enter the organ. Following inflammation, the lymph node swells ∼10 fold in two weeks . Yet, what is the role for tens ion on the FRC network and caps ule, and how are lymphocytes able to enter in conditions that resist swelling remain open ques tions . We s how that tens ion on the FRC network is important to limit the swelling rate of the organ so that the FRC network can grow in a coordinated fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates and a dis organized FRC network in the inflamed lymph node. Growth of the FRC network in turn is expected to releas e tens ion on thes e s tructures and lowers the res is tance to swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of swelling coincides with a thickening of the caps ule, which forms a thick res is tant band around the organ and lowers tens ion on the FRC network to form a new force equilibrium.The FRC and conduit network are further believed to be a privileged s ite of s oluble information within the lymph node, although many details remain uns olved. We s how by 3D ultra-recons truction that FRCs and antigen pres enting cells cover the s urface of conduit s ys tem for more than 99% and we dis cus s the implications for s oluble information exchangeat the conduit level.Finally, there is an ongoing debate in the cancer field whether and how cancer cells in lymph nodes s eed dis tal metas tas es . We s how that cancer cells infus ed into the lymph node can utilize trafficking routes of immune cells and rapidly migrate to blood vessels. Once in the blood circulation, these cells are able to form metastases in distal tissues. acknowledged_ssus: - _id: Bio - _id: PreCl - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Frank P full_name: Assen, Frank P id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87 last_name: Assen orcid: 0000-0003-3470-6119 citation: ama: 'Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. 2019. doi:10.15479/AT:ISTA:6947' apa: 'Assen, F. P. (2019). Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6947' chicago: 'Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6947.' ieee: 'F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking,” Institute of Science and Technology Austria, 2019.' ista: 'Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria.' mla: 'Assen, Frank P. Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6947.' short: 'F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and Technology Austria, 2019.' date_created: 2019-10-14T16:54:52Z date_published: 2019-10-09T00:00:00Z date_updated: 2023-09-13T08:50:57Z day: '9' ddc: - '570' degree_awarded: PhD department: - _id: MiSi doi: 10.15479/AT:ISTA:6947 file: - access_level: closed checksum: 53a739752a500f84d0f8ec953cbbd0b6 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: fassen date_created: 2019-11-06T12:30:02Z date_updated: 2020-11-07T23:30:03Z embargo_to: open_access file_id: '6990' file_name: PhDthesis_FrankAssen_revised2.docx file_size: 214172667 relation: source_file - access_level: open_access checksum: 8c156b65d9347bb599623a4b09f15d15 content_type: application/pdf creator: fassen date_created: 2019-11-06T12:30:57Z date_updated: 2020-11-07T23:30:03Z embargo: 2020-11-06 file_id: '6991' file_name: PhDthesis_FrankAssen_revised2.pdf file_size: 83637532 relation: main_file file_date_updated: 2020-11-07T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '142' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '664' relation: part_of_dissertation status: public - id: '402' 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: 'Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking' type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6891' abstract: - lang: eng text: "While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 citation: ama: Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:10.15479/AT:ISTA:6891 apa: Kopf, A. (2019). The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6891 chicago: Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6891. ieee: A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019. ista: Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. mla: Kopf, Aglaja. The Implication of Cytoskeletal Dynamics on Leukocyte Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6891. short: A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019. date_created: 2019-09-19T08:19:44Z date_published: 2019-07-24T00:00:00Z date_updated: 2023-10-18T08:49:17Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: MiSi doi: 10.15479/AT:ISTA:6891 file: - access_level: closed checksum: 00d100d6468e31e583051e0a006b640c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: akopf date_created: 2019-10-15T05:28:42Z date_updated: 2020-10-17T22:30:03Z embargo_to: open_access file_id: '6950' file_name: Kopf_PhD_Thesis.docx file_size: 74735267 relation: source_file - access_level: open_access checksum: 5d1baa899993ae6ca81aebebe1797000 content_type: application/pdf creator: akopf date_created: 2019-10-15T05:28:47Z date_updated: 2020-10-17T22:30:03Z embargo: 2020-10-16 file_id: '6951' file_name: Kopf_PhD_Thesis1.pdf file_size: 52787224 relation: main_file file_date_updated: 2020-10-17T22:30:03Z has_accepted_license: '1' keyword: - cell biology - immunology - leukocyte - migration - microfluidics language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '171' project: - _id: 265E2996-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01250-B20 name: Nano-Analytics of Cellular Systems publication_identifier: eissn: - 2663-337X isbn: - 978-3-99078-002-2 publication_status: published publisher: Institute of Science and Technology Austria related_material: link: - relation: press_release url: https://ist.ac.at/en/news/feeling-like-a-cell/ record: - id: '6328' relation: part_of_dissertation status: public - id: '15' relation: part_of_dissertation status: public - id: '6877' 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: The implication of cytoskeletal dynamics on leukocyte migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6328' abstract: - lang: eng text: During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion. acknowledged_ssus: - _id: SSU article_processing_charge: No article_type: letter_note author: - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp - first_name: Ingrid full_name: de Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: de Vries - first_name: Meghan K. full_name: Driscoll, Meghan K. last_name: Driscoll - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Erik S. full_name: Welf, Erik S. last_name: Welf - first_name: Gaudenz full_name: Danuser, Gaudenz last_name: Danuser - first_name: Reto full_name: Fiolka, Reto last_name: Fiolka - 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, Kopf A, Stopp JA, et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 2019;568:546-550. doi:10.1038/s41586-019-1087-5 apa: Renkawitz, J., Kopf, A., Stopp, J. A., de Vries, I., Driscoll, M. K., Merrin, J., … Sixt, M. K. (2019). Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1087-5 chicago: Renkawitz, Jörg, Aglaja Kopf, Julian A Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature. Springer Nature, 2019. https://doi.org/10.1038/s41586-019-1087-5. ieee: J. Renkawitz et al., “Nuclear positioning facilitates amoeboid migration along the path of least resistance,” Nature, vol. 568. Springer Nature, pp. 546–550, 2019. ista: Renkawitz J, Kopf A, Stopp JA, de Vries I, Driscoll MK, Merrin J, Hauschild R, Welf ES, Danuser G, Fiolka R, Sixt MK. 2019. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 568, 546–550. mla: Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature, vol. 568, Springer Nature, 2019, pp. 546–50, doi:10.1038/s41586-019-1087-5. short: J. Renkawitz, A. Kopf, J.A. Stopp, I. de Vries, M.K. Driscoll, J. Merrin, R. Hauschild, E.S. Welf, G. Danuser, R. Fiolka, M.K. Sixt, Nature 568 (2019) 546–550. date_created: 2019-04-17T06:52:28Z date_published: 2019-04-25T00:00:00Z date_updated: 2024-03-27T23:30:39Z day: '25' department: - _id: MiSi - _id: NanoFab - _id: Bio doi: 10.1038/s41586-019-1087-5 ec_funded: 1 external_id: isi: - '000465594200050' pmid: - '30944468' intvolume: ' 568' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/ month: '04' oa: 1 oa_version: Submitted Version page: 546-550 pmid: 1 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 265FAEBA-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01250-B20 name: Nano-Analytics of Cellular Systems - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 25A48D24-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1396-2014 name: Molecular and system level view of immune cell migration publication: Nature 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/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/ record: - id: '14697' relation: dissertation_contains status: public - id: '6891' relation: dissertation_contains status: public scopus_import: '1' status: public title: Nuclear positioning facilitates amoeboid migration along the path of least resistance type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 568 year: '2019' ... --- _id: '6877' article_processing_charge: No article_type: original author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - 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: Kopf A, Sixt MK. The neural crest pitches in to remove apoptotic debris. Cell. 2019;179(1):51-53. doi:10.1016/j.cell.2019.08.047 apa: Kopf, A., & Sixt, M. K. (2019). The neural crest pitches in to remove apoptotic debris. Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.08.047 chicago: Kopf, Aglaja, and Michael K Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.08.047. ieee: A. Kopf and M. K. Sixt, “The neural crest pitches in to remove apoptotic debris,” Cell, vol. 179, no. 1. Elsevier, pp. 51–53, 2019. ista: Kopf A, Sixt MK. 2019. The neural crest pitches in to remove apoptotic debris. Cell. 179(1), 51–53. mla: Kopf, Aglaja, and Michael K. Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” Cell, vol. 179, no. 1, Elsevier, 2019, pp. 51–53, doi:10.1016/j.cell.2019.08.047. short: A. Kopf, M.K. Sixt, Cell 179 (2019) 51–53. date_created: 2019-09-15T22:00:46Z date_published: 2019-09-19T00:00:00Z date_updated: 2024-03-27T23:30:40Z day: '19' department: - _id: MiSi doi: 10.1016/j.cell.2019.08.047 external_id: isi: - '000486618500011' pmid: - '31539498' intvolume: ' 179' isi: 1 issue: '1' language: - iso: eng month: '09' oa_version: None page: 51-53 pmid: 1 publication: Cell publication_identifier: eissn: - 1097-4172 issn: - 0092-8674 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '6891' relation: dissertation_contains status: public scopus_import: '1' status: public title: The neural crest pitches in to remove apoptotic debris type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 179 year: '2019' ...