The creation of nanoscale computers for use in precision healthcare has long been a dream of many researchers and healthcare providers. Now, for the first time, researchers at Penn State have produced a nanocomputer that can control the function of a particular protein involved in cell motions and cancer metastases. The research paves the way for the construction of complex nanoscale computers for the prevention and treatment of cancer and other diseases.
Nikolay Dokholyan, G. Thomas Passananti Professor, Penn State College of Medicine, and his colleagues – including Yashavantha Vishweshwaraiah, postdoc of pharmacology, Penn State – created a transistor-like ‘logic gate’, a form of computation operation in which multiple inputs control an output.
“Our logical gate is only the beginning of what might be called cellular computing,” he said, “but it is an important milestone because it demonstrates the ability to embed conditional operations in a protein and control its function,” Dokholyan said. “It will allow us to gain a deeper understanding of human biology and disease and introduce opportunities for the development of precision therapy.”
The team’s logical gate consisted of two sensor domains designed to respond to two inputs – light and the drug rapamycin. The team targeted the protein focal adhesion kinase (FAK) because it is involved in cell adhesion and movement, which are the first steps in the development of metastatic cancer.
“First, we introduced a rapamycin-sensitive domain, called uniRapr, which the laboratory had previously designed and studied, into the gene encoding FAK,” said Vishweshwaraiah. “Next, we introduced the domain, LOV2, which is sensitive to light. Once we had optimized both domains, we combined them into a final logic-gate design.”
The team inserted the modified gene into HeLa cancer cells and observed the cells in vitro using confocal microscopy. They examined the effects of each of the inputs separately, as well as the combined effect of the inputs, on the behavior of the cells.
They discovered that not only could they quickly activate FAK using light and rapamycin, but also that this activation resulted in the cells undergoing internal changes that improved their adhesiveness, ultimately reducing their motility.
Their results published today (November 16) in the journal Nature communication.
“We are showing for the first time that we can build a working nanocomputer in living cells that can control cell behavior,” Vishweshwaraiah said. “We also discovered some interesting features of the FAK protein, such as the changes it triggers in cells when activated.”
Dokholyan noted that the team hopes to eventually test these nanocomputers in vivo in living organisms.
Other Penn State writers on paper include Jiaxing Chen, a graduate student; Venkat R. Chirasani, postdoc; and Erdem D. Tabdanov, Assistant Professor of Pharmacology.
Transforming cells into computers with protein logic gates
Nature communication (2021). DOI: 10.1038 / s41467-021-26937-x
Provided by Pennsylvania State University
Citation: Nanoscale ‘computer’ controls protein function, affects cell behavior (2021, November 16) Retrieved November 16, 2021 from https://phys.org/news/2021-11-nanoscale-function-protein-cell-behavior.html
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