Issue 11, 2024

Graphene oxide activates canonical TGFβ signalling in a human chondrocyte cell line via increased plasma membrane tension

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.

Graphical abstract: Graphene oxide activates canonical TGFβ signalling in a human chondrocyte cell line via increased plasma membrane tension

Supplementary files

Article information

Article type
Paper
Submitted
27 11 2023
Accepted
18 2 2024
First published
19 2 2024
This article is Open Access
Creative Commons BY license

Nanoscale, 2024,16, 5653-5664

Graphene oxide activates canonical TGFβ signalling in a human chondrocyte cell line via increased plasma membrane tension

L. Ogene, S. Woods, J. Hetmanski, N. Lozano, A. Karakasidi, P. T. Caswell, K. Kostarelos, M. A. N. Domingos, S. Vranic and S. J. Kimber, Nanoscale, 2024, 16, 5653 DOI: 10.1039/D3NR06033K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements