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Nucleocytoplasmic transport senses mechanical forces independently of cell density in cell monolayers.
Granero-Moya, Ignasi; Venturini, Valeria; Belthier, Guillaume; Groenen, Bart; Molina-Jordán, Marc; González-Martín, Miguel; Trepat, Xavier; van Rheenen, Jacco; Andreu, Ion; Roca-Cusachs, Pere.
Afiliación
  • Granero-Moya I; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08014 Barcelona, Spain.
  • Venturini V; University of Barcelona, 08036 Barcelona, Spain.
  • Belthier G; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08014 Barcelona, Spain.
  • Groenen B; Oncode Institute, 1066 CX Amsterdam, The Netherlands.
  • Molina-Jordán M; Department of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
  • González-Martín M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08014 Barcelona, Spain.
  • Trepat X; Eindhoven University of Technology, Department of Biomedical Engineering, PO Box 513, 5600 MB Eindhoven, The Netherlands.
  • van Rheenen J; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08014 Barcelona, Spain.
  • Andreu I; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08014 Barcelona, Spain.
  • Roca-Cusachs P; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 08014 Barcelona, Spain.
J Cell Sci ; 137(17)2024 Sep 01.
Article en En | MEDLINE | ID: mdl-39120491
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Celular / Transporte Activo de Núcleo Celular / Mecanotransducción Celular Límite: Animals / Humans Idioma: En Revista: J Cell Sci Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Celular / Transporte Activo de Núcleo Celular / Mecanotransducción Celular Límite: Animals / Humans Idioma: En Revista: J Cell Sci Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido