To date, scientists’ understanding of how cells communicate with each other has been limited, in large part because the electrical activity of cells has been limited to simple, 2D measurements. However, that may change soon, thanks to research being led by Carnegie Mellon University faculty.
Tzahi Cohen-Karni, an assistant professor of biomedical engineering and materials science and engineering at Carnegie Mellon, is developing nanosensors to monitor the electrical activity of cells in three dimensions — a feat that until now has not been possible. Cohen-Karni recently received an NSF CAREER award for his project, which aims to understand how cells talk to each other in three dimensions.
“We, as humans, are not two-dimensional,” Cohen-Karni said. “When you culture cells in a dish, it is not as they are organized in nature. We are trying to measure the electrophysiology of a cellular arrangement that is closer to the way it is in nature.”
Traditionally, cells are cultured in two dimensions, on a 2D flat surface where researchers cannot get a full sense of the electrical activity happening in a close to natural 3D geometry. Current techniques that measure in 3D only monitor the surface of one side of the cellular arrangement. However, Cohen-Karni’s technique surrounds the 3D cell construct with sensors and monitors it from all sides.
This project has huge long-term implications. In the biological field, heart cells, or cardiomyocytes, serve as a potential therapy for heart defects and conditions. Monitoring these cells in 3D will provide more insight into the way cells really communicate.
“When it comes to the heart and the brain,” Cohen-Karni said, “whatever we do is due to this intracellular communication. To some extent, we know what is happening inside. But having the tools to explore it in a quasi-controlled manner will help us to understand exactly how they talk to each other.”
Cohen-Karni’s sensors are made of nanowires that are 1,000 times smaller than the diameter of a human hair and will measure the electrophysiology of 3D cell constructs that are a few times larger than a human hair diameter. The nanomaterial that makes up the devices is synthesized within Cohen-Karni’s lab and then assembled into sensors in the form of field effect transistors.
Cohen-Karni’s nanosensors surround the cells in a series of steps. First, the nanosensors are attached to a strip of polymer only a few hundred microns long, on a chip lined with thin strips of metal, which serve as leads to the nanosensors and lift the polymer from the surface of the chip. When the polymer is released from the surface of the chip, it self-rolls around the cells into a three-dimensional barrel-like entity. The nanosensors on the polymer surround the cells and are able to take measurements from all sides.
Cohen-Karni’s device will monitor the electrophysiology of induced pluripotent cells derived cardiomyocytes (iPS-CM). In the future, the platform will be able to compare the electrical activity of normal heart or brain cells with that of diseased cells.
“It’s the idea of monitoring something that is not on a plane-that’s the big idea,” Cohen-Karni said. “You take something that was for years pinned on a surface, and kick it out.”