Graphene oxide activates canonical TGFβ signalling in a human chondrocyte cell line via increased plasma membrane tension
Ogene, Leona (The University of Manchester)
Woods, Steven (The University of Manchester)
Hetmanski, Joseph (University of Manchester)
Lozano, Neus (Institut Català de Nanociència i Nanotecnologia)
Karakasidi, Angeliki (The University of Manchester)
Caswell, Patrick T. (University of Manchester)
Kostarelos, Kostas (Institut Català de Nanociència i Nanotecnologia)
Domingos, Maco A.N. (The University of Manchester. Department of Solids and Structure, School of Engineering)
Vranic, Sandra (The University of Manchester)
Kimber, Susan J. (The University of Manchester)

Data:	2024
Resum:	Graphene Oxide (GO) has been shown to increase the expression of key cartilage genes and matrix components within 3D scaffolds. Understanding the mechanisms behind the chondroinductive ability of GO is critical for developing articular cartilage regeneration therapies but remains poorly understood. The objectives of this work were to elucidate the effects of GO on the key chondrogenic signalling pathway - TGFβ and identify the mechanism through which signal activation is achieved in human chondrocytes. Activation of canonical signalling was validated through GO-induced SMAD-2 phosphorylation and upregulation of known TGFβ response genes, while the use of a TGFβ signalling reporter assay allowed us to identify the onset of GO-induced signal activation which has not been previously reported. Importantly, we investigate the cell-material interactions and molecular mechanisms behind these effects, establishing a novel link between GO, the plasma membrane and intracellular signalling. By leveraging fluorescent lifetime imaging (FLIM) and a membrane tension probe, we reveal GO-mediated increases in plasma membrane tension, in real-time for the first time. Furthermore, we report the activation of mechanosensory pathways which are known to be regulated by changes in plasma membrane tension and reveal the activation of endogenous latent TGFβ in the presence of GO, providing a mechanism for signal activation. The data presented here are critical to understanding the chondroinductive properties of GO and are important for the implementation of GO in regenerative medicine.
Ajuts:	Agencia Estatal de Investigación CEX2021-001214-S Agencia Estatal de Investigación SEV-2017-0706
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nanoscale, Vol. 16, Issue 11 (March 2024) , p. 5653-5664, ISSN 2040-3372

DOI: 10.1039/d3nr06033k
PMID: 38414413

12 p, 3.0 MB

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