Nucleocytoplasmic transport senses mechanical forces independently of cell density in cell monolayers
Cells sense and respond to mechanical forces through mechanotransduction, which regulates processes in health and disease. In single adhesive cells, mechanotransduction involves the transmission of force from the extracellular matrix to the cell nucleus, where it affects nucleocytoplasmic transport (NCT) and the subsequent nuclear localization of transcriptional regulators, such as YAP (also known as YAP1). However, if and how NCT is mechanosensitive in multicellular systems is unclear. Here, we characterize and use a fluorescent sensor of nucleocytoplasmic transport (Sencyt) and demonstrate that NCT responds to mechanical forces but not cell density in cell monolayers. Using monolayers of both epithelial and mesenchymal phenotype, we show that NCT is altered in response both to osmotic shocks and to the inhibition of cell contractility. Furthermore, NCT correlates with the degree of nuclear deformation measured through nuclear solidity, a shape parameter related to nuclear envelope tension. In contrast, YAP is sensitive to cell density, showing that the YAP response to cell-cell contacts is not via a mere mechanical effect of NCT. Our results demonstrate the generality of the mechanical regulation of NCT.
Authors
- Ignasi Granero-Moya (ORCID: https://orcid.org/0000-0003-2554-9318)
- Marc Molina-Jordán (ORCID: https://orcid.org/0000-0001-7484-8918)
- Valeria Venturini (ORCID: https://orcid.org/0000-0003-2526-6473)
- Xavier Trepat (ORCID: https://orcid.org/0000-0002-7621-5214)
- Ion Andreu (ORCID: https://orcid.org/0000-0002-8374-152X)
- Pere Roca‐Cusachs (ORCID: https://orcid.org/0000-0001-6947-961X)
- Bart Groenen (ORCID: https://orcid.org/0000-0002-0790-3494)
- Jacco van Rheenen (ORCID: https://orcid.org/0000-0001-8175-1647)
- Guillaume Belthier (ORCID: https://orcid.org/0000-0002-4857-0008)
- Miguel González-Martín
Institutions
- Ikerbasque (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- The Netherlands Cancer Institute (NL)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Oncode Institute (NL)
- Instituto Biofisika (ES)
- Fundación Biofísica Bizkaia (ES)
- Barcelona Institute of Science and Technology (ES)
- Institute for Bioengineering of Catalonia (ES)
- Universitat de Barcelona (ES)
- Eindhoven University of Technology (NL)
Publication Details
- Journal
- Journal of Cell Science
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1242/jcs.262363
- Citations
- 9
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 2.93
Funders
- Fundació la Marató de TV3
- Generalitat de Catalunya
- Eusko Jaurlaritza
- Institució Catalana de Recerca i Estudis Avançats
- Ministerio de Ciencia e Innovación
- Universitat de Barcelona