@ARTICLE{10.3389/fcell.2020.00678, AUTHOR={Domingues, Catarina and Geraldo, A. Margarida and Anjo, Sandra Isabel and Matos, André and Almeida, Cláudio and Caramelo, Inês and Lopes-da-Silva, José A. and Paiva, Artur and Carvalho, João and Pires das Neves, Ricardo and Manadas, Bruno and Grãos, Mário}, TITLE={Cofilin-1 Is a Mechanosensitive Regulator of Transcription}, JOURNAL={Frontiers in Cell and Developmental Biology}, VOLUME={8}, YEAR={2020}, URL={https://www.frontiersin.org/articles/10.3389/fcell.2020.00678}, DOI={10.3389/fcell.2020.00678}, ISSN={2296-634X}, ABSTRACT={The mechanical properties of the extracellular environment are interrogated by cells and integrated through mechanotransduction. Many cellular processes depend on actomyosin-dependent contractility, which is influenced by the microenvironment’s stiffness. Here, we explored the influence of substrate stiffness on the proteome of proliferating undifferentiated human umbilical cord-matrix mesenchymal stem/stromal cells. The relative abundance of several proteins changed significantly by expanding cells on soft (∼3 kPa) or stiff substrates (GPa). Many such proteins are associated with the regulation of the actin cytoskeleton, a major player of mechanotransduction and cell physiology in response to mechanical cues. Specifically, Cofilin-1 levels were elevated in cells cultured on soft comparing with stiff substrates. Furthermore, Cofilin-1 was de-phosphorylated (active) and present in the nuclei of cells kept on soft substrates, in contrast with phosphorylated (inactive) and widespread distribution in cells on stiff. Soft substrates promoted Cofilin-1-dependent increased RNA transcription and faster RNA polymerase II-mediated transcription elongation. Cofilin-1 is part of a novel mechanism linking mechanotransduction and transcription.} }