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Title: | Graphene oxide activates canonical TGFβ signalling in a human chondrocyte cell line <i>via</i> increased plasma membrane tension |
Authors: | Ogene, L Woods, S Hetmanski, J Lozano, N Karakasidi, A Caswell, PT Kostarelos, K Domingos, MAN Vranic, S Kimber, SJ |
Issue Date: | 19-Feb-2024 |
Publisher: | Royal Society of Chemistry |
Citation: | Ogene, L. et al. (2024) 'Graphene oxide activates canonical TGFβ signalling in a human chondrocyte cell line <i>via</i> increased plasma membrane tension', Nanoscale, 16 (11), pp. 5653 - 5664. doi: 10.1039/d3nr06033k. |
Abstract: | 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. |
Description: | Data availability:
No new data. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Footnote: Electronic supplementary information (ESI) available. See doi: https://doi.org/10.1039/d3nr06033k . |
URI: | https://bura.brunel.ac.uk/handle/2438/28528 |
DOI: | https://doi.org/10.1039/d3nr06033k |
ISSN: | 2040-3364 |
Other Identifiers: | ORCiD: Leona Ogene https://orcid.org/0000-0003-2041-4377 ORCiD: Joseph Hetmanski https://orcid.org/0000-0002-1493-351X ORCiD: Neus Lozano https://orcid.org/0000-0002-9026-1743 ORCiD: Kostas Kostarelos https://orcid.org/0000-0002-2224-6672 ORCiD: Marco A. N. Domingos https://orcid.org/0000-0002-6693-790X ORCiD: Sandra Vranic https://orcid.org/0000-0002-6653-7156 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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