Many scientists and health professionals have long dreamed of creating nanoscale computers that can be used for precision health treatment. Now, for the first time, researchers at Penn State have produced a nanocomputing agent that can control the function of a particular protein that is involved in cell movement and cancer metastasis. This research opens the doors to the development of advanced nanoscale computers that can be used to treat and prevention of cancer and other diseases.
Nikolay Dokholyan is the G. Thomas Passananti Professor at the Penn State College of Medicine. He and his colleagues – which includes Yashavantha Vishiwaiah who is an assistant professor in the field of pharmacology at Penn State – created a transistor-like logic gate’, which is a kind of computation that has multiple inputs control the output of.
“Our logic gate is just the beginning of what you can call cellular computing,” he said, “but it is a significant step because it shows the ability to embed conditional functions into a protein and control its function, said Dokholyan. “It will enable us to gain a better understanding of the human body’s biology and diseases and opens up possibilities for the development of precise treatments.”
The logic gate of the team comprised of two sensor domains which could respond to light or drug rapamycin. Because it is involved with cell adhesion and movement (which are the first steps in metastatic cancer development) the team targeted the protein focal adhesionkinase (FAK).
Vishweshwaraiah said that “first we introduced the rapamycin sensitive domain, known as uniRapr that the lab previously designed and studied, into the gene that encodes FAK.” “Next we introduced the domain, LOV2 which is sensitive to light. After optimizing both domains, we combined them to create a logic gate design.”
The modified gene was introduced into HeLa cancer cells. Confocal microscopy was utilized to observe the cells in the laboratory. They examined the effects of each input separately and also the combined effects of the inputs, on the cells and their behavior.
They found that they not only were they able to rapidly activate FAK with light and rapamycin, but that activation led to the cells going through internal changes that increased their adhesive capabilities, which ultimately reduced their mobility.
Their results published today (Nov. 16) in the journal Nature Communications.
“We show for the first time that we can construct a functioning nanocomputing agent in living cells that can influence the behavior of cells,” said Vishweshwaraiah. “We also identified interesting properties in the FAK protein, such as the changes it triggers within cells when activated.”
Dokholyan said that the group hopes to eventually test the nanocomputing agents in vivo with living organisms.
Other Penn State authors on the paper include Jiaxing Chen, a graduate student; Venkat R. Chirasani postdoctoral fellow, and Erdem D. Tabdanov, assistant professor of pharmacology.
The National Institutes of Health and the Passan Foundation supported this research.
Vishweshwaraiah, Y.L., et al. (2021) Two-input protein logic gate to perform computation in living cells. Nature Communications. doi.org/10.1038/s41467-021-26937-x.
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