{"acknowledgement":"We thank Jan Ellenberg (SciLifeLab), Stephan Grill (MPI-CBG), Anna Erzberger (EMBL) and members of the Diz-Muñoz lab for a critical reading of the manuscript. We thank Estela Sosa Osorio (EMBL) and Gisela Juliachs Torroella (EMBL) for manual curation of actin segmentation in cryo-electron tomograms, and Evgenia Zagoriy (EMBL) and Mukthi Ammai Sridharan Iyer (EMBL) for the visual inspection of actin branching points in cryo-electron tomograms. We thank Anne-Cecyle Reyman (IGBMC) and her team for extended discussion and inspiring experiments. We thank Ruben Tesoro Moreno (EMBL) for Alphafold predictions. We thank Jan Faix (Hannover Medical School) for the mDia1 constructs and Jamie Hackett (EMBL Rome) for the Piggybac vectors. We thank Sarah Kaspar in the EMBL Data Science Centre for help with statistical methods. We thank the EMBL Flow Cytometry Core Facility (especially Daniel Gimenes), the EMBL advanced light microscopy facility (especially Marko Lampe and Beate Neumann for microscope support, and Christian Tischer for help with image analysis), EMBL IT (especially Thomas Hoffmann), and the EMBL cryo-EM platform for support and advice. We thank Albert Dominguez Mantes (EPFL) for helpful discussions about Spotiflow. We acknowledge the financial support of the European Molecular Biology Laboratory (EMBL) to J.M. and A.D-M., the Deutsche Forschungsgemeinschaft (DFG) grant DI 2205/3-1, the Human Frontiers Science Program (HFSP) grant RGY0073/2018 and ERC grant 101124221 (MitoMeChAnics) to A.D-M., the Boehringer Ingelheim Fonds PhD fellowship and the Croucher Scholarship for Doctoral Study to D.C., the EMBL interdisciplinary Postdoc (EIPOD) programme under Marie Curie Cofund Actions MSCA-COFUND-FP to M.S. and M.T-N., the EMBO fellowship to S.F.G., the French Agence Nationale de la Recherche (ANR-21-CE13-0048) to O.D.R. and J.H.; This work is partially funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. Open Access funding enabled and organized by Projekt DEAL.","doi":"10.1038/s41467-026-72845-3","quality_controlled":"1","volume":17,"year":"2026","status":"public","dataavailabilitystatement":"The dataset for the analysis of cortical actin and p-myosin in fixed cells, as well as actin and myosin−2 in live cells can be found together with the corresponding Fiji macro for immunofluorescence quantification in the Biostudies database (accession number S-BIAD2611).\r\n\r\nAll raw frames, tilt series, metadata, tomograms and segmentations generated for this work are deposited in the Electron Microscopy Public Image Archive (EMPIAR)118 under accession code EMPIAR-13326. A representative tomogram associated with this entry is available in the Electron Microscopy Data Bank (EMDB)119 under entry EMD-56367.\r\n\r\nThe experimental imaging data for the filopodia analysis, the used Spotiflow model with corresponding training data and example datasets are available in the BioStudies database (accession number S-BIAD2611).\r\n\r\nRaw numbers for plots presented in this paper as well as western blot images are available in the Source Data. All other data and unique reagents that support this study are available from the corresponding authors upon request. Source data are provided in this paper. Source data are provided with this paper.\r\nThe code used for cortex analysis from binary segmentations obtained during cryo-ET data processing is available on GitHub with the following link: https://github.com/MahamidLab/actin_cortex_analysis/tree/revision.\r\n\r\nThe Napari plugin for reviewing and manually correct spot detections used in the filopodia analysis is available at GitHub with the following link: https://github.com/diz-lab/filospot.","date_published":"2026-09-04T00:00:00Z","PlanS_conform":"1","_id":"22911","intvolume":"        17","citation":{"ieee":"L. Strauss <i>et al.</i>, “The membrane-to-cortex distance regulates mDia1 activity to control cortical mechanics,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026.","mla":"Strauss, Léanne, et al. “The Membrane-to-Cortex Distance Regulates MDia1 Activity to Control Cortical Mechanics.” <i>Nature Communications</i>, vol. 17, 9501, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-72845-3\">10.1038/s41467-026-72845-3</a>.","chicago":"Strauss, Léanne, Sergio Lembo, Samuel F. Gérard, Marc Siggel, Dorothy Cheng, Martin Bergert, Sarah K. Foster, et al. “The Membrane-to-Cortex Distance Regulates MDia1 Activity to Control Cortical Mechanics.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-72845-3\">https://doi.org/10.1038/s41467-026-72845-3</a>.","ama":"Strauss L, Lembo S, Gérard SF, et al. The membrane-to-cortex distance regulates mDia1 activity to control cortical mechanics. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-72845-3\">10.1038/s41467-026-72845-3</a>","apa":"Strauss, L., Lembo, S., Gérard, S. F., Siggel, M., Cheng, D., Bergert, M., … Diz-Muñoz, A. (2026). The membrane-to-cortex distance regulates mDia1 activity to control cortical mechanics. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-72845-3\">https://doi.org/10.1038/s41467-026-72845-3</a>","short":"L. Strauss, S. Lembo, S.F. Gérard, M. Siggel, D. Cheng, M. Bergert, S.K. Foster, J. Vermeil, M. Toro-Nahuelpan, L.M. Fischer, Q. Yu, E. Sitarska, C.J. Chan, J. Kosinski, M. Piel, O. Du Roure, J. Heuvingh, J. Mahamid, A. Diz-Muñoz, Nature Communications 17 (2026).","ista":"Strauss L, Lembo S, Gérard SF, Siggel M, Cheng D, Bergert M, Foster SK, Vermeil J, Toro-Nahuelpan M, Fischer LM, Yu Q, Sitarska E, Chan CJ, Kosinski J, Piel M, Du Roure O, Heuvingh J, Mahamid J, Diz-Muñoz A. 2026. The membrane-to-cortex distance regulates mDia1 activity to control cortical mechanics. Nature Communications. 17, 9501."},"publication_identifier":{"eissn":["2041-1723"]},"DOAJ_listed":"1","publisher":"Springer Nature","publication_status":"published","abstract":[{"text":"The shape of animal cells is controlled by their surface, which comprises the cell cortex, a peripheral actin network, tethered to the plasma membrane by membrane-to-cortex attachment proteins. Changes in cortical components have long been considered to dominate the regulation of forces and mechanical properties at the cell surface and drive morphogenesis. Here, we show that the coupling of the cortex to the membrane is also key for the regulation of its mechanical properties. By combining molecular engineering with biophysical approaches and in-cell cryo-electron tomography we describe the cell surface with nanometer-resolution and link its organization to cell-scale mechanics. We find that membrane-to-cortex attachment proteins can physically draw the cortex closer to the membrane, in a density and length-dependent manner. This reduction of the membrane-to-cortex distance controls the activity of the formin mDia1, leading to a reduction in cortical tension. Our study thus defines a novel mechanism whereby the membrane-to-cortex distance is a functional geometrical parameter that regulates cell surface properties.","lang":"eng"}],"corr_author":"1","oa_version":"Published Version","tmp":{"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)","image":"/images/cc_by.png"},"pmid":1,"language":[{"iso":"eng"}],"scopus_import":"1","department":[{"_id":"MiSi"}],"oa":1,"article_number":"9501","article_processing_charge":"Yes (via OA deal)","ddc":["570"],"license":"https://creativecommons.org/licenses/by/4.0/","month":"09","file_date_updated":"2026-09-15T12:51:36Z","researchdata_availability":"yes","fulldoi":"https://doi.org/10.1038/s41467-026-72845-3","date_updated":"2026-09-15T12:58:06Z","supplementarymaterial":"yes","OA_place":"publisher","date_created":"2026-09-13T22:01:51Z","publication":"Nature Communications","has_accepted_license":"1","title":"The membrane-to-cortex distance regulates mDia1 activity to control cortical mechanics","article_type":"original","file":[{"file_id":"22932","content_type":"application/pdf","checksum":"adc0d16fcb2a65e1a5913481700fa19f","date_created":"2026-09-15T12:51:36Z","file_size":3154967,"file_name":"2026_NatureComm_Strauss.pdf","date_updated":"2026-09-15T12:51:36Z","access_level":"open_access","relation":"main_file","success":1,"creator":"dernst"}],"das_tickbox":"1","OA_type":"gold","external_id":{"pmid":["42697882"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","day":"04","author":[{"last_name":"Strauss","first_name":"Léanne","full_name":"Strauss, Léanne"},{"first_name":"Sergio","last_name":"Lembo","id":"d993a7b2-292f-11ed-aaac-fb045a912e31","full_name":"Lembo, Sergio","orcid":"0000-0002-2253-8771"},{"last_name":"Gérard","first_name":"Samuel F.","full_name":"Gérard, Samuel F."},{"full_name":"Siggel, Marc","last_name":"Siggel","first_name":"Marc"},{"full_name":"Cheng, Dorothy","first_name":"Dorothy","last_name":"Cheng"},{"first_name":"Martin","last_name":"Bergert","full_name":"Bergert, Martin"},{"first_name":"Sarah K.","last_name":"Foster","full_name":"Foster, Sarah K."},{"full_name":"Vermeil, Joseph","last_name":"Vermeil","first_name":"Joseph"},{"last_name":"Toro-Nahuelpan","first_name":"Mauricio","full_name":"Toro-Nahuelpan, Mauricio"},{"last_name":"Fischer","first_name":"Lena M.","full_name":"Fischer, Lena M."},{"first_name":"Qin","last_name":"Yu","full_name":"Yu, Qin"},{"first_name":"Ewa","last_name":"Sitarska","full_name":"Sitarska, Ewa"},{"full_name":"Chan, Chii Jou","last_name":"Chan","first_name":"Chii Jou"},{"first_name":"Jan","last_name":"Kosinski","full_name":"Kosinski, Jan"},{"full_name":"Piel, Matthieu","last_name":"Piel","first_name":"Matthieu"},{"full_name":"Du Roure, Olivia","first_name":"Olivia","last_name":"Du Roure"},{"full_name":"Heuvingh, Julien","first_name":"Julien","last_name":"Heuvingh"},{"full_name":"Mahamid, Julia","first_name":"Julia","last_name":"Mahamid"},{"last_name":"Diz-Muñoz","first_name":"Alba","full_name":"Diz-Muñoz, Alba"}]}