Traditional synthetic biology approaches to cell-based therapies, such as those that kill cancer cells or promote tissue regeneration after injury, rely on the expression or suppression of proteins that produce a desired action within a cell. Basically it is about preventing or encouraging a cell to perform a certain function. This approach can take time, one necessary for proteins to be expressed and degraded. And that costs cellular energy. Now a team of scientists from Pennsylvania State University, led by Nikolay Dokholyan, has created the first protein-based nanocomputing agent that works like a circuit.
“We are designing proteins that directly produce a desired action,” Dokholyan explains. “Our protein-based devices or nanocomputing agents respond directly to stimuli (inputs) and then produce a desired action (outputs).”
In the study, published in Science Advances, the authors describe how they designed a target protein by integrating two sensors that respond to stimuli. In this case, the target protein responds to light and a drug called rapamycin by adjusting its orientation or position in space. To test their design, the team introduced their modified protein into living cells in culture. During exposure of cultured cells to stimuli, changes in cell orientation were measured.
In previous studies, Dokholyan’s team had designed a similar system only that it needed two inputs or stimuli to produce an output. Now there are two possible outputs and that output depends on the order in which the stimuli are received. If rapamycin is detected first, followed by light, the cell will assume one cell orientation angle, but if the stimuli are received in reverse order, the cell will assume a different orientation angle. This experimental proof of concept opens the door for the development of more complex nanocomputing agents.
“Theoretically, the more inputs you incorporate into a nanocomputing agent, the more potential results could result from different combinations,” says Jiaxing Chen, co-author of the study. Potential inputs could include physical or chemical stimuli and outputs could include changes in cell behaviors, such as cell steering, migration, modification of gene expression, and immune cell cytotoxicity against cancer cells.”
The team plans to further develop their nanocomputing agents and experiment with different applications so that they may one day be used in cell-based therapies for autoimmune diseases, viral infections, diabetes, nerve injury and cancer.
