Chem
Volume 1, Issue 2, 11 August 2016, Pages 273-286
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Article
Graphene Oxide Nanosheets Stimulate Ruffling and Shedding of Mammalian Cell Plasma Membranes

https://doi.org/10.1016/j.chempr.2016.06.019Get rights and content
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Highlights

  • Graphene oxide (GO) induces ruffling and shedding of mammalian cell plasma membranes

  • GO-induced plasma membrane responses induce loss of contact inhibition in RBL cells

  • GO-treated plasma membranes undergo nuanced structural and functional changes

The Bigger Picture

It is essential to understand the biological effects of nanomaterials to safely and effectively deploy them in living cells. Graphene oxide (GO) is a leading candidate material for use within biological systems because of its low cost, water solubility, and low toxicity. Here, we identified changes in mammalian cell behavior and the plasma membranes in the presence of GO. GO induces dramatic ruffling and shedding of plasma membranes, which correlates with the formation of uncharacteristic multilayers in these cells. These findings should encourage others to look for non-lethal cellular responses by GO or GO composites in other contexts. Once the biochemical basis of these effects is better understood, GO's ability to present multiple functional chemical handles and modulate cellular responses might be exploited for tissue engineering, stem cell differentiation, or reducing the invasiveness of cancer cells.

Summary

Graphene oxide (GO) has attracted intense interest for use in living systems and environmental applications. GO's compatibility with mammalian cells is sometimes inferred from its low cytotoxicity, but such conclusions ignore non-lethal effects that will influence GO's utility. Here, we used confocal and live-cell fluorescence microscopy, as well as scanning electron microscopy, of rat basophilic leukemia (RBL) cells to demonstrate profound plasma membrane (PM) ruffling and shedding induced by GO. These membrane structures contain immunoglobulin E receptors, are resistant to detergents, and lack detectable fluorescence labeling of F-actin and fibronectin. The formation of these membrane structures correlates with a loss of contact inhibition between RBL cells. We observed similar cellular responses toward GO for NIH-3T3 fibroblast cells and MDA-MB-231 human breast cancer cells. These findings reveal a previously uncharacterized cellular response toward foreign nanomaterials. Membrane ruffling and shedding raise fundamental questions about how GO interacts with the PM, as well as its potential to modulate cellular mechanosensing for tissue engineering, stem cell differentiation, and other biomedical applications.

UN Sustainable Development Goals

SDG3: Good health and well-being

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