Cholesterol’s Role in the Response to Graphene
Due to its interesting array of physical and chemical properties, graphene is the focus of exciting new applications in biomedical research, drug delivery, neuroprosthetics, and tissue engineering. However, little is known about how graphene interacts with cells or its potential toxicity. Prior work demonstrated substantial toxicity of graphene flakes in bacteria, but other studies have suggested that eukaryotic cells can be grown on graphene surfaces with limited harmful effects. To explain these disparate results, Vanderbilt Basic Sciences investigator Qi Zhang and his lab hypothesized that the differences might be explained by the fact that cholesterol or similar steroids are present in eukaryotic cells but absent in bacteria. To test this hypothesis, they first showed that cholesterol readily binds to graphene flakes under cell culture conditions and that rat neuronal cells grown on a graphene surface exhibit higher membrane cholesterol levels than cells grown on glass. Compared to glass-grown cells, neuronal cells grown on graphene also demonstrated an increase in excitability, as indicated by a higher frequency of spontaneous excitatory post-synaptic potentials. The researchers attributed this to an increase in the number of synaptic vesicles responsible for neurotransmitter release. Depletion of membrane cholesterol in graphene-exposed cells eliminated the observed increased excitability, whereas cholesterol supplementation of cells grown on glass resulted in excitability levels similar to those observed in cells grown on graphene. Further studies revealed that graphene exposure also led to increased membrane cholesterol in NIH 3T3 cells, accompanied by facilitated ATP-stimulated calcium signaling by the P2YR receptor. The findings demonstrate that cholesterol plays a key role in the response of mammalian cells to graphene and that graphene-mediated changes in cholesterol levels can modulate important membrane-associated cellular functions. Further work will be required to determine how this important interaction can best be exploited for future bioapplications of graphene. The work is published in the journal Nature Communications [K. E. Kitko, et al. Nat. Commun., (2018) 9, 796].