Nanocomputing Agents Respond to Stimuli


Penn State Scientists have created the first protein-based nanocomputing agent that functions as a circuit. This achievement brings them closer to developing the next generation of cell-based therapies to treat diseases such as diabetes and cancer.

Intuitive Nano-Computing Agents Respond to Stimuli, Producing Desired Actions

Jiaxing Chen, a bioinformatics and genomics doctoral student at Penn State College of Medicine and Penn State Huck Institutes of the Life Sciences, was part of a Penn State research team to create the first protein-based nanocomputing agents that function as circuits. Image Credit: Penn State Huck / Penn State Institute of Life Sciences

Conventional synthetic biology techniques for cell-based therapies, such as those that kill cancer cells or enhance tissue regeneration after injury, rely on the expression or suppression of proteins that perform desired actions within cells. This method takes time (for protein to be expressed and degraded) and consumes cellular energy. A research team from Penn State College of Medicine and Huck Institutes of the Life Sciences is trying a new approach.

We engineer proteins that directly produce the desired actions. Our protein-based devices or nanocomputing agents respond directly to stimuli (input) and then produce the desired action (output)..

Nikolay Dokholian, G. Thomas Passananti Professor and Deputy Chair, Department of Pharmacology, Pennsylvania State University

Doctoral student Jiaxing Chen and bioinformatics and genomics detail their strategy for building their nanocomputing agent on May 26th2023, in Science Advances. They create target proteins by joining two sensor domains, or regions of the protein that respond to stimuli. In this scenario, the target protein adjusts its orientation, or position in space, in response to light and the drug rapamycin.

To test their discovery, the researchers introduced their modified protein into living cells in culture. They used equipment to evaluate changes in cellular orientation after exposing cultured cells to stimuli from sensory domains.

Their previous nanocomputing agent required two inputs to produce one output. Chen now claims that there are two alternative outputs, and that the outputs are determined by the order in which the inputs are received.

If rapamycin is sensed first, followed by light, the cell will adopt an angular orientation; however, if the stimuli are received in reverse order, the cells will adopt a different orientation angle. This experimental proof-of-concept, according to Chen, paves the way for the development of more complicated nanocomputing agents.

Theoretically, the more inputs you embed into a nanocomputing agent, the more potential results can be generated from different combinations. Potential inputs can include physical or chemical stimuli and outputs can include changes in cellular behavior, such as cell orientation, migration, modification of gene expression, and cytotoxicity of immune cells against cancer cells..

Jiaxing Chen, Doctoral Student, Pennsylvania State University

The group intends to improve their nanocomputing agent and experiment with other uses of the technology. Dokholian, a researcher at the Penn State Cancer Institute and Penn State Neuroscience Institute believes their idea has the potential to form the basis for the next generation of cell-based therapies for diseases such as viral infections, autoimmune diseases, nerve injury, diabetes, and cancer.

Yashavantha Vishweshwaraiah, Richard Mailman, and Erdem Tabdanov of Penn State College of Medicine also contributed to the research. The authors declare that they have no conflict of interest.

The National Institutes of Health (grant 1R35GM134864) and the Passan Foundation supported this research.



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