--- _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: '54' abstract: - lang: eng text: During epithelial tissue development, repair, and homeostasis, adherens junctions (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell and tissue dynamics. Mechanical forces play critical roles in AJs’ composition and dynamics. Recent findings highlight that beyond a well-established role in reinforcing cell-cell adhesion, AJ mechanosensitivity promotes junctional remodeling and polarization, thereby regulating critical processes such as cell intercalation, division, and collective migration. Here, we provide an integrated view of mechanosensing mechanisms that regulate cell-cell contact composition, geometry, and integrity under tension and highlight pivotal roles for mechanosensitive AJ remodeling in preserving epithelial integrity and sustaining tissue dynamics. acknowledgement: Research in the Bellaïche laboratory is supported by the European Research Council (ERC Advanced, TiMoprh, 340784), the Fondation ARC pour la Recherche sur le Cancer (SL220130607097), the Agence Nationale de la Recherche (ANR lLabex DEEP; 11-LBX-0044, ANR-10-IDEX-0001-02), the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, and Institut Curie and PSL Research University funding or grants. article_processing_charge: No article_type: review author: - first_name: Diana C full_name: Nunes Pinheiro, Diana C id: 2E839F16-F248-11E8-B48F-1D18A9856A87 last_name: Nunes Pinheiro orcid: 0000-0003-4333-7503 - first_name: Yohanns full_name: Bellaïche, Yohanns last_name: Bellaïche citation: ama: Nunes Pinheiro DC, Bellaïche Y. Mechanical force-driven adherents junction remodeling and epithelial dynamics. Developmental Cell. 2018;47(1):3-19. doi:10.1016/j.devcel.2018.09.014 apa: Nunes Pinheiro, D. C., & Bellaïche, Y. (2018). Mechanical force-driven adherents junction remodeling and epithelial dynamics. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2018.09.014 chicago: Nunes Pinheiro, Diana C, and Yohanns Bellaïche. “Mechanical Force-Driven Adherents Junction Remodeling and Epithelial Dynamics.” Developmental Cell. Cell Press, 2018. https://doi.org/10.1016/j.devcel.2018.09.014. ieee: D. C. Nunes Pinheiro and Y. Bellaïche, “Mechanical force-driven adherents junction remodeling and epithelial dynamics,” Developmental Cell, vol. 47, no. 1. Cell Press, pp. 3–19, 2018. ista: Nunes Pinheiro DC, Bellaïche Y. 2018. Mechanical force-driven adherents junction remodeling and epithelial dynamics. Developmental Cell. 47(1), 3–19. mla: Nunes Pinheiro, Diana C., and Yohanns Bellaïche. “Mechanical Force-Driven Adherents Junction Remodeling and Epithelial Dynamics.” Developmental Cell, vol. 47, no. 1, Cell Press, 2018, pp. 3–19, doi:10.1016/j.devcel.2018.09.014. short: D.C. Nunes Pinheiro, Y. Bellaïche, Developmental Cell 47 (2018) 3–19. date_created: 2018-12-11T11:44:23Z date_published: 2018-10-08T00:00:00Z date_updated: 2023-09-13T08:54:38Z day: '08' department: - _id: CaHe doi: 10.1016/j.devcel.2018.09.014 external_id: isi: - '000446579900002' intvolume: ' 47' isi: 1 issue: '1' language: - iso: eng main_file_link: - url: https://doi.org/10.1016/j.devcel.2018.09.014 month: '10' oa_version: Published Version page: 3 - 19 publication: Developmental Cell publication_status: published publisher: Cell Press publist_id: '8000' quality_controlled: '1' scopus_import: '1' status: public title: Mechanical force-driven adherents junction remodeling and epithelial dynamics type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 47 year: '2018' ... --- _id: '276' abstract: - lang: eng text: Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controlla-bility of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion-based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL19 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo. acknowledgement: This work was supported by the Swiss National Science Foundation (MD-PhD fellowships, 323530_164221 to C.F.; and 323630_151483 to A.J.; grant PZ00P3_144863 to M.R, grant 31003A_156431 to T.S.; PZ00P3_148000 to C.T.B.; PZ00P3_154733 to M.M.), a Novartis “FreeNovation” grant to M.M. and T.S. and an EMBO long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409) to J.R.. M.R. was supported by the Gebert Rüf Foundation (GRS 058/14). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. article_number: e0198330 article_processing_charge: No article_type: original author: - first_name: Corina full_name: Frick, Corina last_name: Frick - first_name: Philip full_name: Dettinger, Philip last_name: Dettinger - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Annaïse full_name: Jauch, Annaïse last_name: Jauch - first_name: Christoph full_name: Berger, Christoph last_name: Berger - first_name: Mike full_name: Recher, Mike last_name: Recher - first_name: Timm full_name: Schroeder, Timm last_name: Schroeder - first_name: Matthias full_name: Mehling, Matthias last_name: Mehling citation: ama: Frick C, Dettinger P, Renkawitz J, et al. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. 2018;13(6). doi:10.1371/journal.pone.0198330 apa: Frick, C., Dettinger, P., Renkawitz, J., Jauch, A., Berger, C., Recher, M., … Mehling, M. (2018). Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0198330 chicago: Frick, Corina, Philip Dettinger, Jörg Renkawitz, Annaïse Jauch, Christoph Berger, Mike Recher, Timm Schroeder, and Matthias Mehling. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” PLoS One. Public Library of Science, 2018. https://doi.org/10.1371/journal.pone.0198330. ieee: C. Frick et al., “Nano-scale microfluidics to study 3D chemotaxis at the single cell level,” PLoS One, vol. 13, no. 6. Public Library of Science, 2018. ista: Frick C, Dettinger P, Renkawitz J, Jauch A, Berger C, Recher M, Schroeder T, Mehling M. 2018. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. 13(6), e0198330. mla: Frick, Corina, et al. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” PLoS One, vol. 13, no. 6, e0198330, Public Library of Science, 2018, doi:10.1371/journal.pone.0198330. short: C. Frick, P. Dettinger, J. Renkawitz, A. Jauch, C. Berger, M. Recher, T. Schroeder, M. Mehling, PLoS One 13 (2018). date_created: 2018-12-11T11:45:34Z date_published: 2018-06-07T00:00:00Z date_updated: 2023-09-13T09:00:15Z day: '07' ddc: - '570' department: - _id: MiSi doi: 10.1371/journal.pone.0198330 external_id: isi: - '000434384900031' file: - access_level: open_access checksum: 95fc5dc3938b3ad3b7697d10c83cc143 content_type: application/pdf creator: dernst date_created: 2018-12-17T14:10:32Z date_updated: 2020-07-14T12:45:45Z file_id: '5709' file_name: 2018_Plos_Frick.pdf file_size: 7682167 relation: main_file file_date_updated: 2020-07-14T12:45:45Z has_accepted_license: '1' intvolume: ' 13' isi: 1 issue: '6' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '06' oa: 1 oa_version: Published Version publication: PLoS One publication_status: published publisher: Public Library of Science publist_id: '7626' quality_controlled: '1' scopus_import: '1' status: public title: Nano-scale microfluidics to study 3D chemotaxis at the single cell level 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 13 year: '2018' ... --- _id: '283' abstract: - lang: eng text: Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors. article_number: '8754' article_processing_charge: No author: - first_name: Rosa Maria full_name: Ceinos, Rosa Maria last_name: Ceinos - first_name: Elena full_name: Frigato, Elena last_name: Frigato - first_name: Cristina full_name: Pagano, Cristina last_name: Pagano - first_name: Nadine full_name: Frohlich, Nadine last_name: Frohlich - first_name: Pietro full_name: Negrini, Pietro last_name: Negrini - first_name: Nicola full_name: Cavallari, Nicola id: 457160E6-F248-11E8-B48F-1D18A9856A87 last_name: Cavallari - first_name: Daniela full_name: Vallone, Daniela last_name: Vallone - first_name: Silvia full_name: Fuselli, Silvia last_name: Fuselli - first_name: Cristiano full_name: Bertolucci, Cristiano last_name: Bertolucci - first_name: Nicholas S full_name: Foulkes, Nicholas S last_name: Foulkes citation: ama: Ceinos RM, Frigato E, Pagano C, et al. Mutations in blind cavefish target the light regulated circadian clock gene period 2. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-27080-2 apa: Ceinos, R. M., Frigato, E., Pagano, C., Frohlich, N., Negrini, P., Cavallari, N., … Foulkes, N. S. (2018). Mutations in blind cavefish target the light regulated circadian clock gene period 2. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/s41598-018-27080-2 chicago: Ceinos, Rosa Maria, Elena Frigato, Cristina Pagano, Nadine Frohlich, Pietro Negrini, Nicola Cavallari, Daniela Vallone, Silvia Fuselli, Cristiano Bertolucci, and Nicholas S Foulkes. “Mutations in Blind Cavefish Target the Light Regulated Circadian Clock Gene Period 2.” Scientific Reports. Nature Publishing Group, 2018. https://doi.org/10.1038/s41598-018-27080-2. ieee: R. M. Ceinos et al., “Mutations in blind cavefish target the light regulated circadian clock gene period 2,” Scientific Reports, vol. 8, no. 1. Nature Publishing Group, 2018. ista: Ceinos RM, Frigato E, Pagano C, Frohlich N, Negrini P, Cavallari N, Vallone D, Fuselli S, Bertolucci C, Foulkes NS. 2018. Mutations in blind cavefish target the light regulated circadian clock gene period 2. Scientific Reports. 8(1), 8754. mla: Ceinos, Rosa Maria, et al. “Mutations in Blind Cavefish Target the Light Regulated Circadian Clock Gene Period 2.” Scientific Reports, vol. 8, no. 1, 8754, Nature Publishing Group, 2018, doi:10.1038/s41598-018-27080-2. short: R.M. Ceinos, E. Frigato, C. Pagano, N. Frohlich, P. Negrini, N. Cavallari, D. Vallone, S. Fuselli, C. Bertolucci, N.S. Foulkes, Scientific Reports 8 (2018). date_created: 2018-12-11T11:45:36Z date_published: 2018-06-08T00:00:00Z date_updated: 2023-09-13T08:59:27Z day: '08' ddc: - '570' department: - _id: EvBe doi: 10.1038/s41598-018-27080-2 external_id: isi: - '000434640800008' file: - access_level: open_access checksum: 9c3942d772f84f3df032ffde0ed9a8ea content_type: application/pdf creator: dernst date_created: 2018-12-17T13:04:46Z date_updated: 2020-07-14T12:45:49Z file_id: '5707' file_name: 2018_ScientificReports_Ceinos.pdf file_size: 1855324 relation: main_file file_date_updated: 2020-07-14T12:45:49Z has_accepted_license: '1' intvolume: ' 8' isi: 1 issue: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version publication: Scientific Reports publication_status: published publisher: Nature Publishing Group publist_id: '7616' quality_controlled: '1' scopus_import: '1' status: public title: Mutations in blind cavefish target the light regulated circadian clock gene period 2 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 8 year: '2018' ... --- _id: '81' abstract: - lang: eng text: We solve the offline monitoring problem for timed propositional temporal logic (TPTL), interpreted over dense-time Boolean signals. The variant of TPTL we consider extends linear temporal logic (LTL) with clock variables and reset quantifiers, providing a mechanism to specify real-time constraints. We first describe a general monitoring algorithm based on an exhaustive computation of the set of satisfying clock assignments as a finite union of zones. We then propose a specialized monitoring algorithm for the one-variable case using a partition of the time domain based on the notion of region equivalence, whose complexity is linear in the length of the signal, thereby generalizing a known result regarding the monitoring of metric temporal logic (MTL). The region and zone representations of time constraints are known from timed automata verification and can also be used in the discrete-time case. Our prototype implementation appears to outperform previous discrete-time implementations of TPTL monitoring, alternative_title: - LNCS article_processing_charge: No author: - first_name: Adrian full_name: Elgyütt, Adrian id: 4A2E9DBA-F248-11E8-B48F-1D18A9856A87 last_name: Elgyütt - first_name: Thomas full_name: Ferrere, Thomas id: 40960E6E-F248-11E8-B48F-1D18A9856A87 last_name: Ferrere orcid: 0000-0001-5199-3143 - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 citation: ama: 'Elgyütt A, Ferrere T, Henzinger TA. Monitoring temporal logic with clock variables. In: Vol 11022. Springer; 2018:53-70. doi:10.1007/978-3-030-00151-3_4' apa: 'Elgyütt, A., Ferrere, T., & Henzinger, T. A. (2018). Monitoring temporal logic with clock variables (Vol. 11022, pp. 53–70). Presented at the FORMATS: Formal Modeling and Analysis of Timed Systems, Beijing, China: Springer. https://doi.org/10.1007/978-3-030-00151-3_4' chicago: Elgyütt, Adrian, Thomas Ferrere, and Thomas A Henzinger. “Monitoring Temporal Logic with Clock Variables,” 11022:53–70. Springer, 2018. https://doi.org/10.1007/978-3-030-00151-3_4. ieee: 'A. Elgyütt, T. Ferrere, and T. A. Henzinger, “Monitoring temporal logic with clock variables,” presented at the FORMATS: Formal Modeling and Analysis of Timed Systems, Beijing, China, 2018, vol. 11022, pp. 53–70.' ista: 'Elgyütt A, Ferrere T, Henzinger TA. 2018. Monitoring temporal logic with clock variables. FORMATS: Formal Modeling and Analysis of Timed Systems, LNCS, vol. 11022, 53–70.' mla: Elgyütt, Adrian, et al. Monitoring Temporal Logic with Clock Variables. Vol. 11022, Springer, 2018, pp. 53–70, doi:10.1007/978-3-030-00151-3_4. short: A. Elgyütt, T. Ferrere, T.A. Henzinger, in:, Springer, 2018, pp. 53–70. conference: end_date: 2018-09-06 location: Beijing, China name: 'FORMATS: Formal Modeling and Analysis of Timed Systems' start_date: 2018-09-04 date_created: 2018-12-11T11:44:31Z date_published: 2018-08-26T00:00:00Z date_updated: 2023-09-13T08:58:34Z day: '26' ddc: - '000' department: - _id: ToHe doi: 10.1007/978-3-030-00151-3_4 external_id: isi: - '000884993200004' file: - access_level: open_access checksum: e5d81c9b50a6bd9d8a2c16953aad7e23 content_type: application/pdf creator: dernst date_created: 2020-10-09T06:24:21Z date_updated: 2020-10-09T06:24:21Z file_id: '8638' file_name: 2018_LNCS_Elgyuett.pdf file_size: 537219 relation: main_file success: 1 file_date_updated: 2020-10-09T06:24:21Z has_accepted_license: '1' intvolume: ' 11022' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Submitted Version page: 53 - 70 project: - _id: 25F5A88A-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S11402-N23 name: Moderne Concurrency Paradigms - _id: 25F42A32-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z211 name: The Wittgenstein Prize publication_status: published publisher: Springer publist_id: '7973' quality_controlled: '1' scopus_import: '1' status: public title: Monitoring temporal logic with clock variables type: conference user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 11022 year: '2018' ...