--- _id: '6490' abstract: - lang: eng text: "Smart contracts are programs that are stored and executed on the Blockchain and can receive, manage and transfer money (cryptocurrency units). Two important problems regarding smart contracts are formal analysis and compiler optimization. Formal analysis is extremely important, because smart contracts hold funds worth billions of dollars and their code is immutable after deployment. Hence, an undetected bug can cause significant financial losses. Compiler optimization is also crucial, because every action of a smart contract has to be executed by every node in the Blockchain network. Therefore, optimizations in compiling smart contracts can lead to significant savings in computation, time and energy.\r\n\r\nTwo classical approaches in program analysis and compiler optimization are intraprocedural and interprocedural analysis. In intraprocedural analysis, each function is analyzed separately, while interprocedural analysis considers the entire program. In both cases, the analyses are usually reduced to graph problems over the control flow graph (CFG) of the program. These graph problems are often computationally expensive. Hence, there has been ample research on exploiting structural properties of CFGs for efficient algorithms. One such well-studied property is the treewidth, which is a measure of tree-likeness of graphs. It is known that intraprocedural CFGs of structured programs have treewidth at most 6, whereas the interprocedural treewidth cannot be bounded. This result has been used as a basis for many efficient intraprocedural analyses.\r\n\r\nIn this paper, we explore the idea of exploiting the treewidth of smart contracts for formal analysis and compiler optimization. First, similar to classical programs, we show that the intraprocedural treewidth of structured Solidity and Vyper smart contracts is at most 9. Second, for global analysis, we prove that the interprocedural treewidth of structured smart contracts is bounded by 10 and, in sharp contrast with classical programs, treewidth-based algorithms can be easily applied for interprocedural analysis. Finally, we supplement our theoretical results with experiments using a tool we implemented for computing treewidth of smart contracts and show that the treewidth is much lower in practice. We use 36,764 real-world Ethereum smart contracts as benchmarks and find that they have an average treewidth of at most 3.35 for the intraprocedural case and 3.65 for the interprocedural case.\r\n" article_processing_charge: No author: - first_name: Krishnendu full_name: Chatterjee, Krishnendu id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87 last_name: Chatterjee orcid: 0000-0002-4561-241X - first_name: Amir Kafshdar full_name: Goharshady, Amir Kafshdar id: 391365CE-F248-11E8-B48F-1D18A9856A87 last_name: Goharshady orcid: 0000-0003-1702-6584 - first_name: Ehsan Kafshdar full_name: Goharshady, Ehsan Kafshdar last_name: Goharshady citation: ama: 'Chatterjee K, Goharshady AK, Goharshady EK. The treewidth of smart contracts. In: Proceedings of the 34th ACM Symposium on Applied Computing. Vol Part F147772. ACM; :400-408. doi:10.1145/3297280.3297322' apa: 'Chatterjee, K., Goharshady, A. K., & Goharshady, E. K. (n.d.). The treewidth of smart contracts. In Proceedings of the 34th ACM Symposium on Applied Computing (Vol. Part F147772, pp. 400–408). Limassol, Cyprus: ACM. https://doi.org/10.1145/3297280.3297322' chicago: Chatterjee, Krishnendu, Amir Kafshdar Goharshady, and Ehsan Kafshdar Goharshady. “The Treewidth of Smart Contracts.” In Proceedings of the 34th ACM Symposium on Applied Computing, Part F147772:400–408. ACM, n.d. https://doi.org/10.1145/3297280.3297322. ieee: K. Chatterjee, A. K. Goharshady, and E. K. Goharshady, “The treewidth of smart contracts,” in Proceedings of the 34th ACM Symposium on Applied Computing, Limassol, Cyprus, vol. Part F147772, pp. 400–408. ista: 'Chatterjee K, Goharshady AK, Goharshady EK. The treewidth of smart contracts. Proceedings of the 34th ACM Symposium on Applied Computing. SAC: Symposium on Applied Computing vol. Part F147772, 400–408.' mla: Chatterjee, Krishnendu, et al. “The Treewidth of Smart Contracts.” Proceedings of the 34th ACM Symposium on Applied Computing, vol. Part F147772, ACM, pp. 400–08, doi:10.1145/3297280.3297322. short: K. Chatterjee, A.K. Goharshady, E.K. Goharshady, in:, Proceedings of the 34th ACM Symposium on Applied Computing, ACM, n.d., pp. 400–408. conference: end_date: 2019-04-12 location: Limassol, Cyprus name: 'SAC: Symposium on Applied Computing' start_date: 2019-04-08 date_created: 2019-05-26T21:59:15Z date_published: 2019-04-01T00:00:00Z date_updated: 2024-03-27T23:30:33Z day: '01' ddc: - '000' department: - _id: KrCh doi: 10.1145/3297280.3297322 external_id: isi: - '000474685800052' file: - access_level: open_access checksum: dddc20f6d9881f23b8755eb720ec9d6f content_type: application/pdf creator: dernst date_created: 2020-05-14T09:50:11Z date_updated: 2020-07-14T12:47:32Z file_id: '7827' file_name: 2019_ACM_Chatterjee.pdf file_size: 6937138 relation: main_file file_date_updated: 2020-07-14T12:47:32Z has_accepted_license: '1' isi: 1 language: - iso: eng month: '04' oa: 1 oa_version: Submitted Version page: 400-408 publication: Proceedings of the 34th ACM Symposium on Applied Computing publication_identifier: isbn: - '9781450359337' publication_status: submitted publisher: ACM pubrep_id: '1070' quality_controlled: '1' related_material: record: - id: '8934' relation: dissertation_contains status: public scopus_import: '1' status: public title: The treewidth of smart contracts type: conference user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: Part F147772 year: '2019' ... --- _id: '7158' abstract: - lang: eng text: "Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, and so on. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, and so on. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is fixed as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in an important algorithmic distinction between the resource usage of the one-time preprocessing vs for each individual query. The second aspect we consider is that the control flow graphs for most programs have constant treewidth.\r\n\r\nOur main contributions are simple and implementable algorithms that support multiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing but can answer subsequent queries significantly faster as compared to the current algorithmic solutions for interprocedural dataflow analysis. We have also implemented our algorithms and evaluated their performance for performing on-demand interprocedural dataflow analysis on various domains, such as for live variable analysis and reaching definitions, on a standard benchmark set. Our experimental results align with our theoretical statements and show that after a lightweight preprocessing, on-demand queries are answered much faster than the standard existing algorithmic approaches.\r\n" article_number: '23' article_processing_charge: No article_type: original author: - first_name: Krishnendu full_name: Chatterjee, Krishnendu id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87 last_name: Chatterjee orcid: 0000-0002-4561-241X - first_name: Amir Kafshdar full_name: Goharshady, Amir Kafshdar id: 391365CE-F248-11E8-B48F-1D18A9856A87 last_name: Goharshady orcid: 0000-0003-1702-6584 - first_name: Prateesh full_name: Goyal, Prateesh last_name: Goyal - first_name: Rasmus full_name: Ibsen-Jensen, Rasmus id: 3B699956-F248-11E8-B48F-1D18A9856A87 last_name: Ibsen-Jensen orcid: 0000-0003-4783-0389 - first_name: Andreas full_name: Pavlogiannis, Andreas id: 49704004-F248-11E8-B48F-1D18A9856A87 last_name: Pavlogiannis orcid: 0000-0002-8943-0722 citation: ama: Chatterjee K, Goharshady AK, Goyal P, Ibsen-Jensen R, Pavlogiannis A. Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth. ACM Transactions on Programming Languages and Systems. 2019;41(4). doi:10.1145/3363525 apa: Chatterjee, K., Goharshady, A. K., Goyal, P., Ibsen-Jensen, R., & Pavlogiannis, A. (2019). Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth. ACM Transactions on Programming Languages and Systems. ACM. https://doi.org/10.1145/3363525 chicago: Chatterjee, Krishnendu, Amir Kafshdar Goharshady, Prateesh Goyal, Rasmus Ibsen-Jensen, and Andreas Pavlogiannis. “Faster Algorithms for Dynamic Algebraic Queries in Basic RSMs with Constant Treewidth.” ACM Transactions on Programming Languages and Systems. ACM, 2019. https://doi.org/10.1145/3363525. ieee: K. Chatterjee, A. K. Goharshady, P. Goyal, R. Ibsen-Jensen, and A. Pavlogiannis, “Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth,” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4. ACM, 2019. ista: Chatterjee K, Goharshady AK, Goyal P, Ibsen-Jensen R, Pavlogiannis A. 2019. Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth. ACM Transactions on Programming Languages and Systems. 41(4), 23. mla: Chatterjee, Krishnendu, et al. “Faster Algorithms for Dynamic Algebraic Queries in Basic RSMs with Constant Treewidth.” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4, 23, ACM, 2019, doi:10.1145/3363525. short: K. Chatterjee, A.K. Goharshady, P. Goyal, R. Ibsen-Jensen, A. Pavlogiannis, ACM Transactions on Programming Languages and Systems 41 (2019). date_created: 2019-12-09T08:33:33Z date_published: 2019-11-01T00:00:00Z date_updated: 2024-03-27T23:30:34Z day: '01' ddc: - '000' department: - _id: KrCh doi: 10.1145/3363525 ec_funded: 1 external_id: isi: - '000564108400004' file: - access_level: open_access checksum: 291cc86a07bd010d4815e177dac57b70 content_type: application/pdf creator: dernst date_created: 2020-10-08T12:58:10Z date_updated: 2020-10-08T12:58:10Z file_id: '8632' file_name: 2019_ACMTransactions_Chatterjee.pdf file_size: 667357 relation: main_file success: 1 file_date_updated: 2020-10-08T12:58:10Z has_accepted_license: '1' intvolume: ' 41' isi: 1 issue: '4' language: - iso: eng month: '11' oa: 1 oa_version: Submitted Version project: - _id: 2584A770-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P 23499-N23 name: Modern Graph Algorithmic Techniques in Formal Verification - _id: 25863FF4-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S11407 name: Game Theory - _id: 2581B60A-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '279307' name: 'Quantitative Graph Games: Theory and Applications' publication: ACM Transactions on Programming Languages and Systems publication_identifier: issn: - 0164-0925 publication_status: published publisher: ACM quality_controlled: '1' related_material: record: - id: '8934' relation: dissertation_contains status: public scopus_import: '1' status: public title: Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 41 year: '2019' ... --- _id: '7014' abstract: - lang: eng text: "We study the problem of developing efficient approaches for proving\r\nworst-case bounds of non-deterministic recursive programs. Ranking functions\r\nare sound and complete for proving termination and worst-case bounds of\r\nnonrecursive programs. First, we apply ranking functions to recursion,\r\nresulting in measure functions. We show that measure functions provide a sound\r\nand complete approach to prove worst-case bounds of non-deterministic recursive\r\nprograms. Our second contribution is the synthesis of measure functions in\r\nnonpolynomial forms. We show that non-polynomial measure functions with\r\nlogarithm and exponentiation can be synthesized through abstraction of\r\nlogarithmic or exponentiation terms, Farkas' Lemma, and Handelman's Theorem\r\nusing linear programming. While previous methods obtain worst-case polynomial\r\nbounds, our approach can synthesize bounds of the form $\\mathcal{O}(n\\log n)$\r\nas well as $\\mathcal{O}(n^r)$ where $r$ is not an integer. We present\r\nexperimental results to demonstrate that our approach can obtain efficiently\r\nworst-case bounds of classical recursive algorithms such as (i) Merge-Sort, the\r\ndivide-and-conquer algorithm for the Closest-Pair problem, where we obtain\r\n$\\mathcal{O}(n \\log n)$ worst-case bound, and (ii) Karatsuba's algorithm for\r\npolynomial multiplication and Strassen's algorithm for matrix multiplication,\r\nwhere we obtain $\\mathcal{O}(n^r)$ bound such that $r$ is not an integer and\r\nclose to the best-known bounds for the respective algorithms." article_number: '20' article_processing_charge: No article_type: original author: - first_name: Krishnendu full_name: Chatterjee, Krishnendu id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87 last_name: Chatterjee orcid: 0000-0002-4561-241X - first_name: Hongfei full_name: Fu, Hongfei last_name: Fu - first_name: Amir Kafshdar full_name: Goharshady, Amir Kafshdar id: 391365CE-F248-11E8-B48F-1D18A9856A87 last_name: Goharshady orcid: 0000-0003-1702-6584 citation: ama: Chatterjee K, Fu H, Goharshady AK. Non-polynomial worst-case analysis of recursive programs. ACM Transactions on Programming Languages and Systems. 2019;41(4). doi:10.1145/3339984 apa: Chatterjee, K., Fu, H., & Goharshady, A. K. (2019). Non-polynomial worst-case analysis of recursive programs. ACM Transactions on Programming Languages and Systems. ACM. https://doi.org/10.1145/3339984 chicago: Chatterjee, Krishnendu, Hongfei Fu, and Amir Kafshdar Goharshady. “Non-Polynomial Worst-Case Analysis of Recursive Programs.” ACM Transactions on Programming Languages and Systems. ACM, 2019. https://doi.org/10.1145/3339984. ieee: K. Chatterjee, H. Fu, and A. K. Goharshady, “Non-polynomial worst-case analysis of recursive programs,” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4. ACM, 2019. ista: Chatterjee K, Fu H, Goharshady AK. 2019. Non-polynomial worst-case analysis of recursive programs. ACM Transactions on Programming Languages and Systems. 41(4), 20. mla: Chatterjee, Krishnendu, et al. “Non-Polynomial Worst-Case Analysis of Recursive Programs.” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4, 20, ACM, 2019, doi:10.1145/3339984. short: K. Chatterjee, H. Fu, A.K. Goharshady, ACM Transactions on Programming Languages and Systems 41 (2019). date_created: 2019-11-13T08:33:43Z date_published: 2019-10-01T00:00:00Z date_updated: 2024-03-27T23:30:33Z day: '01' department: - _id: KrCh doi: 10.1145/3339984 ec_funded: 1 external_id: arxiv: - '1705.00317' isi: - '000564108400001' intvolume: ' 41' isi: 1 issue: '4' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1705.00317 month: '10' oa: 1 oa_version: Preprint project: - _id: 25892FC0-B435-11E9-9278-68D0E5697425 grant_number: ICT15-003 name: Efficient Algorithms for Computer Aided Verification - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 2581B60A-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '279307' name: 'Quantitative Graph Games: Theory and Applications' - _id: 267066CE-B435-11E9-9278-68D0E5697425 name: Quantitative Analysis of Probablistic Systems with a focus on Crypto-currencies - _id: 266EEEC0-B435-11E9-9278-68D0E5697425 name: Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts publication: ACM Transactions on Programming Languages and Systems publication_status: published publisher: ACM quality_controlled: '1' related_material: record: - id: '639' relation: earlier_version status: public - id: '8934' relation: dissertation_contains status: public scopus_import: '1' status: public title: Non-polynomial worst-case analysis of recursive programs type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 41 year: '2019' ... --- _id: '6486' abstract: - lang: eng text: Based on a novel control scheme, where a steady modification of the streamwise velocity profile leads to complete relaminarization of initially fully turbulent pipe flow, we investigate the applicability and usefulness of custom-shaped honeycombs for such control. The custom-shaped honeycombs are used as stationary flow management devices which generate specific modifications of the streamwise velocity profile. Stereoscopic particle image velocimetry and pressure drop measurements are used to investigate and capture the development of the relaminarizing flow downstream these devices. We compare the performance of straight (constant length across the radius of the pipe) honeycombs with custom-shaped ones (variable length across the radius) and try to determine the optimal shape for maximal relaminarization at minimal pressure loss. The optimally modified streamwise velocity profile is found to be M-shaped, and the maximum attainable Reynolds number for total relaminarization is found to be of the order of 10,000. Consequently, the respective reduction in skin friction downstream of the device is almost by a factor of 5. The break-even point, where the additional pressure drop caused by the device is balanced by the savings due to relaminarization and a net gain is obtained, corresponds to a downstream stretch of distances as low as approximately 100 pipe diameters of laminar flow. acknowledged_ssus: - _id: M-Shop article_number: '111105' article_processing_charge: No article_type: original author: - first_name: Jakob full_name: Kühnen, Jakob id: 3A47AE32-F248-11E8-B48F-1D18A9856A87 last_name: Kühnen orcid: 0000-0003-4312-0179 - first_name: Davide full_name: Scarselli, Davide id: 40315C30-F248-11E8-B48F-1D18A9856A87 last_name: Scarselli orcid: 0000-0001-5227-4271 - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 citation: ama: Kühnen J, Scarselli D, Hof B. Relaminarization of pipe flow by means of 3D-printed shaped honeycombs. Journal of Fluids Engineering. 2019;141(11). doi:10.1115/1.4043494 apa: Kühnen, J., Scarselli, D., & Hof, B. (2019). Relaminarization of pipe flow by means of 3D-printed shaped honeycombs. Journal of Fluids Engineering. ASME. https://doi.org/10.1115/1.4043494 chicago: Kühnen, Jakob, Davide Scarselli, and Björn Hof. “Relaminarization of Pipe Flow by Means of 3D-Printed Shaped Honeycombs.” Journal of Fluids Engineering. ASME, 2019. https://doi.org/10.1115/1.4043494. ieee: J. Kühnen, D. Scarselli, and B. Hof, “Relaminarization of pipe flow by means of 3D-printed shaped honeycombs,” Journal of Fluids Engineering, vol. 141, no. 11. ASME, 2019. ista: Kühnen J, Scarselli D, Hof B. 2019. Relaminarization of pipe flow by means of 3D-printed shaped honeycombs. Journal of Fluids Engineering. 141(11), 111105. mla: Kühnen, Jakob, et al. “Relaminarization of Pipe Flow by Means of 3D-Printed Shaped Honeycombs.” Journal of Fluids Engineering, vol. 141, no. 11, 111105, ASME, 2019, doi:10.1115/1.4043494. short: J. Kühnen, D. Scarselli, B. Hof, Journal of Fluids Engineering 141 (2019). date_created: 2019-05-26T21:59:13Z date_published: 2019-11-01T00:00:00Z date_updated: 2024-03-27T23:30:35Z day: '01' department: - _id: BjHo doi: 10.1115/1.4043494 ec_funded: 1 external_id: arxiv: - '1809.07625' isi: - '000487748600005' intvolume: ' 141' isi: 1 issue: '11' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1809.07625 month: '11' oa: 1 oa_version: Preprint project: - _id: 25152F3A-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '306589' name: Decoding the complexity of turbulence at its origin publication: Journal of Fluids Engineering publication_identifier: eissn: - 1528901X issn: - '00982202' publication_status: published publisher: ASME quality_controlled: '1' related_material: record: - id: '7258' relation: dissertation_contains status: public scopus_import: '1' status: public title: Relaminarization of pipe flow by means of 3D-printed shaped honeycombs type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 141 year: '2019' ... --- _id: '6228' abstract: - lang: eng text: Following the recent observation that turbulent pipe flow can be relaminarised bya relatively simple modification of the mean velocity profile, we here carry out aquantitative experimental investigation of this phenomenon. Our study confirms thata flat velocity profile leads to a collapse of turbulence and in order to achieve theblunted profile shape, we employ a moving pipe segment that is briefly and rapidlyshifted in the streamwise direction. The relaminarisation threshold and the minimumshift length and speeds are determined as a function of Reynolds number. Althoughturbulence is still active after the acceleration phase, the modulated profile possessesa severely decreased lift-up potential as measured by transient growth. As shown,this results in an exponential decay of fluctuations and the flow relaminarises. Whilethis method can be easily applied at low to moderate flow speeds, the minimumstreamwise length over which the acceleration needs to act increases linearly with theReynolds number. article_processing_charge: No author: - first_name: Davide full_name: Scarselli, Davide id: 40315C30-F248-11E8-B48F-1D18A9856A87 last_name: Scarselli orcid: 0000-0001-5227-4271 - first_name: Jakob full_name: Kühnen, Jakob id: 3A47AE32-F248-11E8-B48F-1D18A9856A87 last_name: Kühnen orcid: 0000-0003-4312-0179 - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 citation: ama: Scarselli D, Kühnen J, Hof B. Relaminarising pipe flow by wall movement. Journal of Fluid Mechanics. 2019;867:934-948. doi:10.1017/jfm.2019.191 apa: Scarselli, D., Kühnen, J., & Hof, B. (2019). Relaminarising pipe flow by wall movement. Journal of Fluid Mechanics. Cambridge University Press. https://doi.org/10.1017/jfm.2019.191 chicago: Scarselli, Davide, Jakob Kühnen, and Björn Hof. “Relaminarising Pipe Flow by Wall Movement.” Journal of Fluid Mechanics. Cambridge University Press, 2019. https://doi.org/10.1017/jfm.2019.191. ieee: D. Scarselli, J. Kühnen, and B. Hof, “Relaminarising pipe flow by wall movement,” Journal of Fluid Mechanics, vol. 867. Cambridge University Press, pp. 934–948, 2019. ista: Scarselli D, Kühnen J, Hof B. 2019. Relaminarising pipe flow by wall movement. Journal of Fluid Mechanics. 867, 934–948. mla: Scarselli, Davide, et al. “Relaminarising Pipe Flow by Wall Movement.” Journal of Fluid Mechanics, vol. 867, Cambridge University Press, 2019, pp. 934–48, doi:10.1017/jfm.2019.191. short: D. Scarselli, J. Kühnen, B. Hof, Journal of Fluid Mechanics 867 (2019) 934–948. date_created: 2019-04-07T21:59:14Z date_published: 2019-05-25T00:00:00Z date_updated: 2024-03-27T23:30:35Z day: '25' department: - _id: BjHo doi: 10.1017/jfm.2019.191 ec_funded: 1 external_id: arxiv: - '1807.05357' isi: - '000462606100001' intvolume: ' 867' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1807.05357 month: '05' oa: 1 oa_version: Preprint page: 934-948 project: - _id: 25152F3A-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '306589' name: Decoding the complexity of turbulence at its origin - _id: 25104D44-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '737549' name: Eliminating turbulence in oil pipelines publication: Journal of Fluid Mechanics publication_identifier: eissn: - '14697645' issn: - '00221120' publication_status: published publisher: Cambridge University Press quality_controlled: '1' related_material: link: - relation: supplementary_material url: https://doi.org/10.1017/jfm.2019.191 record: - id: '7258' relation: dissertation_contains status: public scopus_import: '1' status: public title: Relaminarising pipe flow by wall movement type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 867 year: '2019' ... --- _id: '6260' abstract: - lang: eng text: Polar auxin transport plays a pivotal role in plant growth and development. PIN auxin efflux carriers regulate directional auxin movement by establishing local auxin maxima, minima, and gradients that drive multiple developmental processes and responses to environmental signals. Auxin has been proposed to modulate its own transport by regulating subcellular PIN trafficking via processes such as clathrin-mediated PIN endocytosis and constitutive recycling. Here, we further investigated the mechanisms by which auxin affects PIN trafficking by screening auxin analogs and identified pinstatic acid (PISA) as a positive modulator of polar auxin transport in Arabidopsis thaliana. PISA had an auxin-like effect on hypocotyl elongation and adventitious root formation via positive regulation of auxin transport. PISA did not activate SCFTIR1/AFB signaling and yet induced PIN accumulation at the cell surface by inhibiting PIN internalization from the plasma membrane. This work demonstrates PISA to be a promising chemical tool to dissect the regulatory mechanisms behind subcellular PIN trafficking and auxin transport. acknowledgement: "We thank Dr. H. Fukaki (University of Kobe), Dr. R. Offringa (Leiden University), Dr. Jianwei Pan (Zhejiang Normal University), and Dr. M. Estelle (University of California at San Diego) for providing mutants and transgenic line seeds.\r\nThis work was supported by the Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Scientific Research no. JP25114518 to K.H.), the Biotechnology and Biological Sciences Research Council (award no. BB/L009366/1 to R.N. and S.K.), and the European Union’s Horizon2020 program (European Research Council grant agreement no. 742985 to J.F.)." article_processing_charge: No article_type: original author: - first_name: A full_name: Oochi, A last_name: Oochi - first_name: Jakub full_name: Hajny, Jakub id: 4800CC20-F248-11E8-B48F-1D18A9856A87 last_name: Hajny orcid: 0000-0003-2140-7195 - first_name: K full_name: Fukui, K last_name: Fukui - first_name: Y full_name: Nakao, Y last_name: Nakao - first_name: Michelle C full_name: Gallei, Michelle C id: 35A03822-F248-11E8-B48F-1D18A9856A87 last_name: Gallei orcid: 0000-0003-1286-7368 - first_name: M full_name: Quareshy, M last_name: Quareshy - first_name: K full_name: Takahashi, K last_name: Takahashi - first_name: T full_name: Kinoshita, T last_name: Kinoshita - first_name: SR full_name: Harborough, SR last_name: Harborough - first_name: S full_name: Kepinski, S last_name: Kepinski - first_name: H full_name: Kasahara, H last_name: Kasahara - first_name: RM full_name: Napier, RM last_name: Napier - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 - first_name: KI full_name: Hayashi, KI last_name: Hayashi citation: ama: Oochi A, Hajny J, Fukui K, et al. Pinstatic acid promotes auxin transport by inhibiting PIN internalization. Plant Physiology. 2019;180(2):1152-1165. doi:10.1104/pp.19.00201 apa: Oochi, A., Hajny, J., Fukui, K., Nakao, Y., Gallei, M. C., Quareshy, M., … Hayashi, K. (2019). Pinstatic acid promotes auxin transport by inhibiting PIN internalization. Plant Physiology. ASPB. https://doi.org/10.1104/pp.19.00201 chicago: Oochi, A, Jakub Hajny, K Fukui, Y Nakao, Michelle C Gallei, M Quareshy, K Takahashi, et al. “Pinstatic Acid Promotes Auxin Transport by Inhibiting PIN Internalization.” Plant Physiology. ASPB, 2019. https://doi.org/10.1104/pp.19.00201. ieee: A. Oochi et al., “Pinstatic acid promotes auxin transport by inhibiting PIN internalization,” Plant Physiology, vol. 180, no. 2. ASPB, pp. 1152–1165, 2019. ista: Oochi A, Hajny J, Fukui K, Nakao Y, Gallei MC, Quareshy M, Takahashi K, Kinoshita T, Harborough S, Kepinski S, Kasahara H, Napier R, Friml J, Hayashi K. 2019. Pinstatic acid promotes auxin transport by inhibiting PIN internalization. Plant Physiology. 180(2), 1152–1165. mla: Oochi, A., et al. “Pinstatic Acid Promotes Auxin Transport by Inhibiting PIN Internalization.” Plant Physiology, vol. 180, no. 2, ASPB, 2019, pp. 1152–65, doi:10.1104/pp.19.00201. short: A. Oochi, J. Hajny, K. Fukui, Y. Nakao, M.C. Gallei, M. Quareshy, K. Takahashi, T. Kinoshita, S. Harborough, S. Kepinski, H. Kasahara, R. Napier, J. Friml, K. Hayashi, Plant Physiology 180 (2019) 1152–1165. date_created: 2019-04-09T08:38:20Z date_published: 2019-06-01T00:00:00Z date_updated: 2024-03-27T23:30:37Z day: '01' department: - _id: JiFr doi: 10.1104/pp.19.00201 ec_funded: 1 external_id: isi: - '000470086100045' pmid: - '30936248' intvolume: ' 180' isi: 1 issue: '2' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1104/pp.19.00201 month: '06' oa: 1 oa_version: Published Version page: 1152-1165 pmid: 1 project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants publication: Plant Physiology publication_identifier: eissn: - 1532-2548 issn: - 0032-0889 publication_status: published publisher: ASPB quality_controlled: '1' related_material: record: - id: '11626' relation: dissertation_contains status: public - id: '8822' relation: dissertation_contains status: public scopus_import: '1' status: public title: Pinstatic acid promotes auxin transport by inhibiting PIN internalization type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 180 year: '2019' ... --- _id: '6508' abstract: - lang: eng text: Segregation of maternal determinants within the oocyte constitutes the first step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming leads to the segregation of ooplasm from yolk granules along the animal-vegetal axis of the oocyte. Here, we show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the oocyte. This wave functions in segregation by both pulling ooplasm animally and pushing yolk granules vegetally. Using biophysical experimentation and theory, we show that ooplasm pulling is mediated by bulk actin network flows exerting friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. Our study defines a novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte polarization via ooplasmic segregation. acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: We would like to thank Pierre Recho, Guillaume Salbreux, and Silvia Grigolon for advice on the theory, Lila Solnica-Krezel for kindly providing us with zebrafish dachsous mutants, members of the Heisenberg and Hannezo groups for fruitful discussions, and the Bioimaging and zebrafish facilities at IST Austria for their continuous support. This project has received funding from the European Union (European Research Council Advanced Grant 742573 to C.P.H.) and from the Austrian Science Fund (FWF) (P 31639 to E.H.). article_processing_charge: No article_type: original author: - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - first_name: Roland full_name: Kardos, Roland id: 4039350E-F248-11E8-B48F-1D18A9856A87 last_name: Kardos - first_name: Shi-lei full_name: Xue, Shi-lei id: 31D2C804-F248-11E8-B48F-1D18A9856A87 last_name: Xue - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. Bulk actin dynamics drive phase segregation in zebrafish oocytes. Cell. 2019;177(6):1463-1479.e18. doi:10.1016/j.cell.2019.04.030 apa: Shamipour, S., Kardos, R., Xue, S., Hof, B., Hannezo, E. B., & Heisenberg, C.-P. J. (2019). Bulk actin dynamics drive phase segregation in zebrafish oocytes. Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.04.030 chicago: Shamipour, Shayan, Roland Kardos, Shi-lei Xue, Björn Hof, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.04.030. ieee: S. Shamipour, R. Kardos, S. Xue, B. Hof, E. B. Hannezo, and C.-P. J. Heisenberg, “Bulk actin dynamics drive phase segregation in zebrafish oocytes,” Cell, vol. 177, no. 6. Elsevier, p. 1463–1479.e18, 2019. ista: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. 2019. Bulk actin dynamics drive phase segregation in zebrafish oocytes. Cell. 177(6), 1463–1479.e18. mla: Shamipour, Shayan, et al. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes.” Cell, vol. 177, no. 6, Elsevier, 2019, p. 1463–1479.e18, doi:10.1016/j.cell.2019.04.030. short: S. Shamipour, R. Kardos, S. Xue, B. Hof, E.B. Hannezo, C.-P.J. Heisenberg, Cell 177 (2019) 1463–1479.e18. date_created: 2019-06-02T21:59:12Z date_published: 2019-05-30T00:00:00Z date_updated: 2024-03-27T23:30:38Z day: '30' ddc: - '570' department: - _id: CaHe - _id: EdHa - _id: BjHo doi: 10.1016/j.cell.2019.04.030 ec_funded: 1 external_id: isi: - '000469415100013' pmid: - '31080065' file: - access_level: open_access checksum: aea43726d80e35ce3885073a5f05c3e3 content_type: application/pdf creator: dernst date_created: 2020-10-21T07:22:34Z date_updated: 2020-10-21T07:22:34Z file_id: '8686' file_name: 2019_Cell_Shamipour_accepted.pdf file_size: 3356292 relation: main_file success: 1 file_date_updated: 2020-10-21T07:22:34Z has_accepted_license: '1' intvolume: ' 177' isi: 1 issue: '6' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.cell.2019.04.030 month: '05' oa: 1 oa_version: Published Version page: 1463-1479.e18 pmid: 1 project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation - _id: 268294B6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P31639 name: Active mechano-chemical description of the cell cytoskeleton publication: Cell publication_identifier: eissn: - '10974172' issn: - '00928674' publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/how-the-cytoplasm-separates-from-the-yolk/ record: - id: '8350' relation: dissertation_contains status: public scopus_import: '1' status: public title: Bulk actin dynamics drive phase segregation in zebrafish oocytes type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 177 year: '2019' ... --- _id: '7001' acknowledged_ssus: - _id: PreCl - _id: Bio article_processing_charge: No article_type: original author: - first_name: Cornelia full_name: Schwayer, Cornelia id: 3436488C-F248-11E8-B48F-1D18A9856A87 last_name: Schwayer orcid: 0000-0001-5130-2226 - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - first_name: Kornelija full_name: Pranjic-Ferscha, Kornelija id: 4362B3C2-F248-11E8-B48F-1D18A9856A87 last_name: Pranjic-Ferscha - first_name: Alexandra full_name: Schauer, Alexandra id: 30A536BA-F248-11E8-B48F-1D18A9856A87 last_name: Schauer orcid: 0000-0001-7659-9142 - first_name: M full_name: Balda, M last_name: Balda - first_name: M full_name: Tada, M last_name: Tada - first_name: K full_name: Matter, K last_name: Matter - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Schwayer C, Shamipour S, Pranjic-Ferscha K, et al. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell. 2019;179(4):937-952.e18. doi:10.1016/j.cell.2019.10.006 apa: Schwayer, C., Shamipour, S., Pranjic-Ferscha, K., Schauer, A., Balda, M., Tada, M., … Heisenberg, C.-P. J. (2019). Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell. Cell Press. https://doi.org/10.1016/j.cell.2019.10.006 chicago: Schwayer, Cornelia, Shayan Shamipour, Kornelija Pranjic-Ferscha, Alexandra Schauer, M Balda, M Tada, K Matter, and Carl-Philipp J Heisenberg. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” Cell. Cell Press, 2019. https://doi.org/10.1016/j.cell.2019.10.006. ieee: C. Schwayer et al., “Mechanosensation of tight junctions depends on ZO-1 phase separation and flow,” Cell, vol. 179, no. 4. Cell Press, p. 937–952.e18, 2019. ista: Schwayer C, Shamipour S, Pranjic-Ferscha K, Schauer A, Balda M, Tada M, Matter K, Heisenberg C-PJ. 2019. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell. 179(4), 937–952.e18. mla: Schwayer, Cornelia, et al. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” Cell, vol. 179, no. 4, Cell Press, 2019, p. 937–952.e18, doi:10.1016/j.cell.2019.10.006. short: C. Schwayer, S. Shamipour, K. Pranjic-Ferscha, A. Schauer, M. Balda, M. Tada, K. Matter, C.-P.J. Heisenberg, Cell 179 (2019) 937–952.e18. date_created: 2019-11-12T12:51:06Z date_published: 2019-10-31T00:00:00Z date_updated: 2024-03-27T23:30:38Z day: '31' ddc: - '570' department: - _id: CaHe - _id: BjHo doi: 10.1016/j.cell.2019.10.006 ec_funded: 1 external_id: isi: - '000493898000012' pmid: - '31675500' file: - access_level: open_access checksum: 33dac4bb77ee630e2666e936b4d57980 content_type: application/pdf creator: dernst date_created: 2020-10-21T07:09:45Z date_updated: 2020-10-21T07:09:45Z file_id: '8684' file_name: 2019_Cell_Schwayer_accepted.pdf file_size: 8805878 relation: main_file success: 1 file_date_updated: 2020-10-21T07:09:45Z has_accepted_license: '1' intvolume: ' 179' isi: 1 issue: '4' language: - iso: eng month: '10' oa: 1 oa_version: Submitted Version page: 937-952.e18 pmid: 1 project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation publication: Cell publication_identifier: eissn: - 1097-4172 issn: - 0092-8674 publication_status: published publisher: Cell Press quality_controlled: '1' related_material: link: - description: News auf IST Website relation: press_release url: https://ist.ac.at/en/news/biochemistry-meets-mechanics-the-sensitive-nature-of-cell-cell-contact-formation-in-embryo-development/ record: - id: '7186' relation: dissertation_contains status: public - id: '8350' relation: dissertation_contains status: public scopus_import: '1' status: public title: Mechanosensation of tight junctions depends on ZO-1 phase separation and flow type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 179 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' ...