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Researchers have developed a technique that allows them to speed up or slow down human heart cells, on command, by shining a light on the cells and varying the light intensity. The optical stimulation platform does not require genetic modification of cells but instead makes use of the optoelectronic properties of graphene, that is, graphene’s ability to efficiently convert light into electricity.
Researchers at the University of California San Diego School of Medicine and their collaborators generated heart cells from donated skin cells via an induced pluripotent stem cell (iPSC). They grew these iPSC-derived heart cells on a graphene surface. Researchers found that the efficiency of stimulation via the graphene biointerface (G-biointerface) was independent of light wavelength but could be tuned by changing the light intensity.
“We were surprised at the degree of flexibility that graphene allows you to pace cells literally at will,” researcher Alex Savchenko said. “You want them to beat twice as fast? No problem — you just increase the light intensity. Three times faster? No problem — increase the light or graphene density.”
Researchers demonstrated that an all-optical evaluation of use-dependent drug effects in vitro could be enabled using substrate-based G-biointerfaces. The team added mexiletine, a medication used to treat arrhythmias, to their heart cells. Mexiletine is known for being use-dependent; it only has an effect when there is an increase in heart rate. The researchers illuminated their heart cells on graphene with light of different intensities. The faster the heart cells beat, the better the mexiletine inhibited them.
Further, using dispersible G-biointerfaces in vivo, the team performed optical modulation of the heart activity in zebrafish embryos.
Researchers observed that cells in the lab grew better on graphene than on other materials, such as glass or plastic, and that cells grown on graphene behaved more like cells do in the body. They also observed an absence of toxicity as a result of introducing a new material (graphene) to the process.
“It makes us hopeful that we’ll be able to avoid harmful problems later on, as we test various medical applications,” Savchenko said.
The new graphene/light system could empower numerous fundamental and translational biomedical studies. Potential applications could include testing therapeutic drugs in more biologically relevant systems, developing use-specific drugs, and creating better medical devices.
The team is interested in eventually applying its graphene/light system to the search for drugs that specifically kill cancer cells, while leaving healthy cells alone. Researchers also envision using graphene to find opioid alternatives — use-dependent pain medications that would only work when and where a person is in pain, thus reducing systemic effects that could lead to misuse. Savchenko also envisions light-controlled pacemakers made of graphene, which could be safer and more effective than current models.
And, he added, “You can squeeze a half-year of animal experiments into a day of experiments with this graphene-based system.”
The research was published in Science Advances (doi:10.1126/sciadv.aat0351).
Mouse heart cells grown on graphene beat at a rate controlled by light stimulation (as indicated by a green circle at top left corner). Here, the cells are also engineered to produce a red fluorescent protein when stimulated by green light. Courtesy of UC San Diego Health.READ MORE