The membrane-to-cortex distance regulates mDia1 activity to control cortical mechanics
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.
Authors
- Dorothy Cheng
- Léanne Strauss (ORCID: https://orcid.org/0000-0002-0680-593X)
- Sergio Lembo (ORCID: https://orcid.org/0000-0002-2253-8771)
- Mauricio Toro‐Nahuelpan (ORCID: https://orcid.org/0000-0001-5333-3640)
- E Sitarska (ORCID: https://orcid.org/0000-0001-6910-0876)
- Jan Kosiński (ORCID: https://orcid.org/0000-0002-3641-0322)
- Julia Mahamid (ORCID: https://orcid.org/0000-0001-6968-041X)
- Martin Bergert (ORCID: https://orcid.org/0000-0002-3222-8929)
- Julien Heuvingh (ORCID: https://orcid.org/0000-0002-6851-584X)
- Joseph Vermeil (ORCID: https://orcid.org/0000-0001-9636-739X)
- Olivia du Roure (ORCID: https://orcid.org/0000-0002-6364-612X)
- Marc Siggel (ORCID: https://orcid.org/0000-0003-3393-4988)
- Matthieu Piel (ORCID: https://orcid.org/0000-0002-2848-177X)
- Alba Diz-Muñoz (ORCID: https://orcid.org/0000-0001-6864-8901)
- Chii Jou Chan (ORCID: https://orcid.org/0000-0003-3177-3949)
- Qin Yu (ORCID: https://orcid.org/0000-0002-4652-0795)
- Samuel F. Gérard
- Sarah K. Foster
- Lena M. Fischer
Institutions
- Boston Children's Hospital (US)
- Centre National de la Recherche Scientifique (FR)
- European Bioinformatics Institute (GB)
- European Molecular Biology Organization (DE)
- Boehringer Ingelheim (Germany) (DE)
- Harvard University (US)
- Institute of Science and Technology Austria (AT)
- National University of Singapore (SG)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- The Francis Crick Institute (GB)
- Sorbonne Université (FR)
- Institut Pierre-Gilles de Gennes pour la Microfluidique (FR)
- Laboratoire Jean Perrin (FR)
- Institut Jacques Monod (FR)
- Physique et Mécanique des Milieux Hétérogènes (FR)
- European Molecular Biology Laboratory (DE)
- Centre for Structural Systems Biology (DE)
- Institut Curie (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-09-04
- DOI
- https://doi.org/10.1038/s41467-026-72845-3
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- École Polytechnique Fédérale de Lausanne
- Medizinischen Hochschule Hannover
- Science for Life Laboratory