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...

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Detalles Bibliográficos
Autores: Granero-Moya, Ignasi, Venturini, Valeria, Belthier, Guillaume, Groenen, Bart, Molina-Jordán, Marc, González-Martín, Miguel, Trepat, Xavier, Rheenen, Jacco van, Andreu, Ion, Roca-Cusachs, Pere
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/373034
Acceso en línea:http://hdl.handle.net/10261/373034
https://api.elsevier.com/content/abstract/scopus_id/85204102069
Access Level:acceso abierto
Palabra clave:Mechanotransduction
Sensor
Mechanobiology
Cell nucleus
Descripción
Sumario: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.