Scientists have created genetic circuits that can be controlled in a variety of ways, such as by light. Now, researchers have found a way to control cellular activity with ultrasound. When ultrasonic waves were applied to either human cells growing in a dish or living mice, a protein channel was stimulated. The findings have been reported in Nature Communications.
Ultrasound is known to be a safe technology that can be used to observe various tissues. Now it may soon be possible to manipulate cells that are deep in the body. "Going wireless is the future for just about everything," said senior study author Sreekanth Chalasani, an associate professor at the Salk Institute's Molecular Neurobiology Laboratory.
Chalasani has been investigating the use of ultrasonic waves to trigger certain genetically tagged cells, naming the technique sonogenetics. His research team has used a roundworm model to show that cells will become sensitive to ultrasound if a protein called TRP4 is added to them. But they found that TRP4 does not make mammalian cells sensitive to ultrasound.
The researchers then began searching for a mammalian protein that could cause ultrasound sensitivity (at a frequency of 7 MHz) in those cells. They began analyzing one protein at a time, studying hundreds to look for one that would cause ultrasound sensitivity in a common cell type used in the research lab called HEK cells. Cells that carried a protein of interest were exposed to ultrasound, and the scientists could monitor how the cells changed.
It took over a year to screen many proteins, and after assessing about 300 of them, the team identified a protein that caused HEK cells to be sensitive to the 7 MHz ultrasound frequency. The protein TRPA1, which creates a membrane channel, normally senses noxious compounds, and can activate biochemical pathways. When TRPA1 is exposed to 7MHz ultrasound, the channel opens.
"We were really surprised," said co-first study author Marc Duque, a Salk exchange student. "TRPA1 has been well-studied in the literature but hasn't been described as a classical mechanosensitive protein that you'd expect to respond to ultrasound."
The human TRPA1 protein was expressed in the brains of genetically engineered, live mice that were then exposed to ultrasound. Only neurons that were engineered to carry human TRPA1 responded to the ultrasound.
Deep brain stimulation is used in therapeutics for several conditions including epilepsy and Parkinson's disease. But in those cases, electrodes are surgically implanted in the brain. Sonogenetics may one day be used in this approach as an alternative to those implants, noted Chalasani. This technique could also be used to treat heart cells, like a pacemaker that doesn't have to be inserted.
"Gene delivery techniques already exist for getting a new gene, such as TRPA1, into the human heart. If we can then use an external ultrasound device to activate those cells, that could really revolutionize pacemakers," Chalasani explained.
The team is learning more about how TRPA1 detects the ultrasonic frequency, and they are looking for other proteins that might be used in similar ways.