article published yes Madeleine T. Schmitt author Janina Kroll author Mauricio J.A. Ruiz-Fernandez author Robert Hauschild author 4E01D6B4-F248-11E8-B48F-1D18A9856A870000-0001-9843-3522 Shaunak Ghosh author Petra Kameritsch author Jack Merrin author 4515C308-F248-11E8-B48F-1D18A9856A870000-0001-5145-4609 Johanna Schmid author Kasia Stefanowski author Andreas W. Thomae author Jingyuan Cheng author Gamze Naz Öztan author Peter Konopka author Germán Camargo Ortega author Thomas Penz author Luisa Bach author Dirk Baumjohann author Christoph Bock author Tobias Straub author Felix Meissner author Eva Kiermaier author 3EB04B78-F248-11E8-B48F-1D18A9856A870000-0001-6165-5738 Jörg Renkawitz author 3F0587C8-F248-11E8-B48F-1D18A9856A870000-0003-2856-3369 Bio department NanoFab department Tools for automation and feedback microscopy project The centrosome is a microtubule orchestrator, nucleating and anchoring microtubules that grow radially and exert forces on cargos. At the same time, mechanical stresses from the microenvironment and cellular shape changes compress and bend microtubules. Yet, centrosomes are membraneless organelles, raising the question of how centrosomes withstand mechanical forces. Here, we discover that centrosomes can deform and even fracture. We reveal that centrosomes experience deformations during navigational pathfinding within motile cells. Coherence of the centrosome is maintained by Dyrk3 and cNAP1, preventing fracturing by forces. While cells can compensate for the depletion of centriolar-based centrosomes, the fracturing of centrosomes impedes cellular function by generating coexisting microtubule organizing centers that compete during path navigation and thereby cause cellular entanglement in the microenvironment. Our findings show that cells actively maintain the integrity of the centrosome to withstand mechanical forces. These results suggest that centrosome stability preservation is fundamental, given that almost all cells in multicellular organisms experience forces. https://research-explorer.ista.ac.at/download/19663/19679/2025_ScienceAdvance_Schmitt.pdf application/pdfno AAAS2025 eng 2375-2548 40279414 00147611340001610.1126/sciadv.adx4047 1117 M.T. Schmitt, J. Kroll, M.J.A. Ruiz-Fernandez, R. Hauschild, S. Ghosh, P. Kameritsch, J. Merrin, J. Schmid, K. Stefanowski, A.W. Thomae, J. Cheng, G.N. Öztan, P. Konopka, G.C. Ortega, T. Penz, L. Bach, D. Baumjohann, C. Bock, T. Straub, F. Meissner, E. Kiermaier, J. Renkawitz, Science Advances 11 (2025). Schmitt, Madeleine T., et al. “Protecting Centrosomes from Fracturing Enables Efficient Cell Navigation.” <i>Science Advances</i>, vol. 11, no. 17, eadx4047, AAAS, 2025, doi:<a href="https://doi.org/10.1126/sciadv.adx4047">10.1126/sciadv.adx4047</a>. Schmitt MT, Kroll J, Ruiz-Fernandez MJA, et al. Protecting centrosomes from fracturing enables efficient cell navigation. <i>Science Advances</i>. 2025;11(17). doi:<a href="https://doi.org/10.1126/sciadv.adx4047">10.1126/sciadv.adx4047</a> Schmitt, M. T., Kroll, J., Ruiz-Fernandez, M. J. A., Hauschild, R., Ghosh, S., Kameritsch, P., … Renkawitz, J. (2025). Protecting centrosomes from fracturing enables efficient cell navigation. <i>Science Advances</i>. AAAS. <a href="https://doi.org/10.1126/sciadv.adx4047">https://doi.org/10.1126/sciadv.adx4047</a> Schmitt MT, Kroll J, Ruiz-Fernandez MJA, Hauschild R, Ghosh S, Kameritsch P, Merrin J, Schmid J, Stefanowski K, Thomae AW, Cheng J, Öztan GN, Konopka P, Ortega GC, Penz T, Bach L, Baumjohann D, Bock C, Straub T, Meissner F, Kiermaier E, Renkawitz J. 2025. Protecting centrosomes from fracturing enables efficient cell navigation. Science Advances. 11(17), eadx4047. Schmitt, Madeleine T., Janina Kroll, Mauricio J.A. Ruiz-Fernandez, Robert Hauschild, Shaunak Ghosh, Petra Kameritsch, Jack Merrin, et al. “Protecting Centrosomes from Fracturing Enables Efficient Cell Navigation.” <i>Science Advances</i>. AAAS, 2025. <a href="https://doi.org/10.1126/sciadv.adx4047">https://doi.org/10.1126/sciadv.adx4047</a>. M. T. Schmitt <i>et al.</i>, “Protecting centrosomes from fracturing enables efficient cell navigation,” <i>Science Advances</i>, vol. 11, no. 17. AAAS, 2025. 196632025-05-11T22:02:38Z2025-09-30T12:26:21Z