Communicating with Cells in Their Natural Language

Researchers have been trying to replicate cells’ system of communication for decades, with no success. Now, Associate Professor Chuanhua Duan (ME, MSE) and colleagues have figured it out. Their biomimetic method of talking to cells might lead to targeted drug delivery, improved prosthetics and other applications.

“Essentially, we’ve cleared the way to communicate with cells using their natural language,” says Duan.

We respond to stimuli because the cells in our bodies communicate with one another and their surroundings by transmitting signals in the form of small chemical molecules. Cells that are set up to receive certain signals each have a receptor for that signal. The cells use protein nanopores— tiny openings that act as gates—to trigger the molecules’ release.

Instead of a door, though, picture a ball on a chain. The ball, made up of amino acids, blocks the pore opening until the correct signal arrives. Then the chain—a string of residues—swings the ball out of the way to let the nanopore open. All this happens in milliseconds, repeatedly.

For nearly two decades, researchers tried to replicate this gating system with artificial devices. “But none of the attempts could completely close the pore,” Duan explains. “And none of them could reach that speed. And none of them could do this reversible gating multiple times.”

And so the trail went cold.

Then in 2018, Duan won a Defense Advanced Research Projects Agency (DARPA) Young Faculty Award to replicate cell-cell information transfer. Along with graduate research assistants Rami Yazbeck (ENG’16,’18,’22) and Yixin Xu (ENG’22) and former ENG faculty member Tyrone Porter, Duan sought to develop the first device that would mimic real-life protein gating.

The team struggled through their own only partially successful attempts before hitting upon a novel solution. They removed the chain from the ball-and-chain gate, used different nanoparticles as the ball and used electrokinetics to drive the nanoparticles to the nanopore.

The result? The gate closes (and opens) completely, rapidly and repeatedly, the first time this gating function has been completely achieved with artificial means.

Someday, devices that use this technology might target a medication to a precise location—such as a tumor—at precise times. The team’s findings were published in Proceedings of the National Academy of Sciences.

Ironically, in nanofluidics, blockage is usually considered a failure, says Duan. “If something blocks the pore, you would think it’s useless. But we essentially converted this from a failure to such exciting potential applications.

“People have asked, ‘How did you guys have this idea?’ But we didn’t have the idea— we learned from nature.” —

PATRICK L. KENNEDY