June 15, 2018 (Vol. 38, No. 12)

Graphene Plates Use Light-Induced Electricity to Make Cardiomyocytes “Beat”

Scientists at the University of California-San Diego (UCSD) have used the ability of graphene to convert light to electricity in order to pace and control heart cells cultured on the semimetal.

The team believes its work opens the door to new avenues of bioelectrical research and novel forms of implantable medical devices.

Graphene is one of those discoveries of materials science with properties that can seem straight from science fiction: A two-dimensional structure of pure carbon, the atoms arranged in a hexagonal lattice one atom thick, graphene has a tensile strength more than 200 times that of steel while weighing in at less than a gram per square meter, and is an excellent electrical conductor—attributes that make graphene appealing for use in everything from consumer electronics to scaffolding for bone tissue engineering.

But it was another property of graphene that interested Alex Savtchenko, a Ph.D. biophysicist and his colleagues at the UCSD School of Medicine, along with his collaborator, biophysicist Elena Molokanova, Ph.D., CEO of Nanotools Bioscience: the fact that graphene efficiently converts light to electric charge.

Dr. Savtchenko wondered if this could be exploited as a means to control the electrical activity of cells such as neurons or cardiomyocytes, heart muscle cells. Cultured cardiomyocytes typically beat at their own rate in a petri dish, Dr. Savtchenko explains. What if graphene could be used to photoelectrically pace the cells cultured on it?

As described in a paper in the May 18 issue of Science Advances, Dr. Savtchenko’s team found exactly this effect—after culturing cardiomyocytes on sheets of graphene, they discovered they could shine a light on the graphene and elicit an action potential, a “beat,” in the cultured cells.

 What’s more, they could control the rate of beat by increasing or decreasing the intensity of the light, an effect Dr. Savtchenko said drew a crowd of grad students and researchers from neighboring labs.

“I was able to actually turn the light and cells like puppies would run faster and you turn that knob up or down, and they run even faster or slower,” he says. “People gathered around asking, ‘Can I turn the knob so I can see this with my own eyes?’”

Illustration of the atomic-scale molecular structure of graphene, a single hexagonal layer of graphite. It is composed of hexagonally arranged carbon atoms linked by strong covalent bonds. Graphene is strong and flexible and transports electrons highly efficiently. [Alfred Pasieka/Science Photo Library/Getty Images]

Elegant Effect

The elegance of such an effect, in a biological experiment, is impressive, says Calum MacRae, M.D., Ph.D., associate professor at Harvard Medical School and until recently the chief of cardiovascular medicine at Brigham and Women’s Hospital, and it’s a discovery that could offer new avenues to researchers interested in how electrical impulses modulate cell behaviors.

“There is a beautiful linearity of response,” he says. “It’s a nice example of how materials science can really begin to have us change the way we think about what we do in biology and biomedicine and they are to be congratulated.”

That was part of the aim going into the study, according to Dr. Savtchenko. While other techniques exist for modulating the electrical activity and signaling of cells, such as direct electrical stimulation or optogenetic techniques, he says, many of those alter the cells in some fashion. His team was looking for a less-invasive method “to elicit some kind of response without perturbing what the cells are supposed to do.”

Cardiomyocytes, like neurons, typically maintain a resting potential of around –70mv to –90mv across the cell membrane, i.e., their interior is more negatively charged than their exterior. When a cell is depolarized to a sufficient degree, say between –70mv to –50mv, it triggers an action potential, the beating of heart cell or an electrical impulse down a neuron’s axon.

Optically stimulated graphene produces excited, negatively charged electrons, which through capacitive charge transfer make the extracellular environment more negative, effectively depolarizing the cells and inducing an action potential, Dr. Savtchenko says.

Moreover, he adds, all human cells in the body exist in an electrically conductive environment, so graphene can provide both basic researchers with a more realistic and controllable tissue model. Outside basic research, he sees initial applications for the new technology in both tissue engineering and drug testing and discovery.

If you want to test a new anti-arrhythmia or anti-tachycardia drug, for instance, current techniques involve cultured cardiomyocytes that are contracting at their own rate. Graphene could provide a way to pace cardiomyocytes to the exact state the drug is intended to treat. “We can actually create a cardiac arrest with these cells,” Dr. Savtchenko says. “If you apply a lot of light, the cells contract faster and faster…we can apply enough light that they will contract and never relax.”

Tissue Engineering Application

That same technique could be used to improve tissue engineering, according to Dr. Savtchenko. The discovery of human-derived, induced pluripotent stems cells has raised the possibility of growing replacement tissues for damaged organs from cells taken from a patient’s own body, he says, but many tissues, including heart and muscle cells, need to be active in order to grow well. Optically stimulated graphene provides a way to train those tissues in vitro. “We are going to pretty much subject them to a boot camp,” Dr. Savtchenko says.

Further in the future, he sees the possibility of using graphene’s light to charge properties to address certain diseases of the eye, such as retinitis pigmentosa, where implanted graphene could substitute for the loss of photoreceptive cells in the retina.

Dr. MacRae even sees potential uses for graphene that could extend beyond medicine, such as in the lab-grown meat industry, where the ability to contract muscle tissues could give products a more realistic texture. “Maybe the first applications for this is completely outside biology,” he says. “Maybe it’s an implantable payment system? Who knows what it is. There’s just lots of ways something like this could be really useful.”

But Dr. MacRae also says it’s important not to get too far ahead of the basic research and to keep in mind that not every new technology proves better than existing clinical interventions. Dr. Savtchenko’s team, for example, is interested in using graphene as an optically controlled pacemaker, and as part of their study, they successfully used injected graphene flakes to pace the hearts of zebrafish embryos.

But traditional pace-making technology today is so good, Dr. MacRae says, that the level of reliability Dr. Savtchenko’s team demonstrated in their study “would never make it past the first preclinical study with a modern pacemaker.”

Dr. MacRae also suggests cautious optimism around the apparent non-toxicity of graphene to the human body, which could make rejection and scarring less likely with implanted devices such as pacemakers. While there is no evidence graphene interfaces are toxic right now, he says, “it’s also not the first time people thought there would be zero toxicity and there ended up being some.”

It’s true that carbon is abundant in the human body, but structure and electrical properties also matter, he points out. Diamonds are pure carbon, “but you get a foreign body reaction to diamonds and nobody quite understands why.”

But that’s not to say Dr. MacRae isn’t excited about the implications of Dr. Savtchenko’s team’s work, especially in the growing field of electrobiology research, which seeks to understand the way information is encoded in biology and how to modulate that information. It’s a field that requires thinking outside the traditional constraints of biomedicine.

 “The things that we thought were outside medicine or outside biology before, now we realize they are an integral part,” Dr. MacRae says. “We need to think about the interfaces and the interactions between different fields much more. This is a physical manifestation of the interaction between physics, chemistry, and biology. That may be the take-home point right there.”

Previous articleThe Present and Future of Mini Brains
Next articleKinetic Imaging: Using Zebrafish to Study Toxicology