18 August 2010—A living quail embryo's heart can be forced to beat to the pulse of a laser, new research shows. The optical-pacing technique may allow scientists to investigate the origins of genetic defects in the heart and may help create a new class of medical devices.
Biomedical engineers at Case Western Reserve University, in Cleveland, and Vanderbilt University, in Nashville, used a laser beam with a 1.875-micrometer wavelength to force the quail embryo's heartbeat to speed up, changing the way that blood splashes against the walls of the heart. Having shown that they can control the pace of the organ with infrared light, the researchers now hope to test how different heart rates may trigger genetic defects that can later lead to heart failure.
The group chose two- to three-day-old embryos whose hearts each consisted of a single pulsing tube that had not yet looped around into the four chambers typical of an adult mammalian heart. Previous studies have shown that the wall of the cardiac tube is sensitive to different patterns of blood flow, which can trigger varying genetic and molecular responses, potentially causing defects. By inserting the laser right next to the organ and forcing the heart to beat in lockstep with the laser's pulses, the biomedical engineers can now design experiments that will force the blood flow to speed up or slow down, changing the amount of stress placed on the walls of the embryonic heart.
These types of experiments would be much more difficult, if not impossible, using traditional electric pacing techniques, the authors say. "When I dump current into some tissue to stimulate it, the current goes everywhere, and I end up stimulating a large region of tissue," says Michael Jenkins, a biomedical engineer at Case Western Reserve and one of the researchers who reported the breakthrough this week in Nature Photonics. "Optically, we focus a beam, and theoretically we could stimulate a single cell." The authors also showed that optical stimulation did not do immediate damage to the little organ. Electrical stimulation, by contrast, tends to kill off some cells, potentially introducing another variable into experiments.
The engineers also hope that this work might one day lead to an optical pacemaker for humans, but several obstacles remain. For one thing, the mechanisms by which the pulses from the laser control the heart are not fully understood. One theory being investigated holds that the laser's photons are absorbed by water molecules in the heart cells, causing an increase in temperature in the vicinity of those molecules. Certain temperature gradients in a cell seem to cause sodium ions to cross the cell membrane, causing a voltage spike to ripple through the cell and make it contract. The Vanderbilt team had already demonstrated that the technique triggers voltage spikes, called action potentials, in peripheral nerves.
The use of light to directly stimulate cells has only recently come into practice. A slightly more established technique, used in the growing field of optogenetics, also relies on light to trigger responses in cells. But the optogenetic approach involves extracting light-sensitive genes from bacteria and inserting them into mammalian nerve cells. Shining a light on those modified cells then causes sodium channels to open, just as in the cardiac cells.
Broadly speaking, direct optical stimulation is a simpler and more straightforward method because it relies on water molecules rather than bacterial DNA, which must first be painstakingly inserted into each target cell. But Loren Frank, a professor of physiology at the University of California, San Francisco, cautions that there are limitations to the optical stimulation of water molecules. Frank notes that the technique is only likely to work in cells that fire in response to temperature changes and in parts of the body where one type of cell predominates, excluding, for instance, much of the brain, in which neither is necessarily true. The ability to stimulate only a specific subset of neurons instead—flagged by the insertion of light-sensitive genetic material, say—might be the better way to provide the level of control needed to manipulate neural circuits, he says.
The heart, however, is a much less complex organ than the brain. E. Duco Jansen, a professor of biomedical engineering at Vanderbilt who worked on the laser-pacing discovery, hopes that optical techniques can be incorporated into the design of more biocompatible medical devices. Compared with metallic electrodes, glassy fibers are relatively inert, allowing for finer control and fewer unwanted interactions with the surrounding tissue. Unlike their electrical predecessors, optical pacemakers would also be safe in magnetic resonance imaging (MRI) machines, Jenkins notes. And the responsiveness of nerve cells outside the brain—observed both in the spinal cord and in the peripheral nervous system—to pulses of light bodes well for a broader category of optical devices, Jansen says.
"We now have a device with beautiful spatial resolution, an enabling tool for studying congenital heart defects," Jansen says. "But can we use this for controlling prosthetic limbs? Can we mimic true motor functions? These are the kinds of questions I'd like to start answering."