Any thought you’ve ever had, any motion you’ve ever made, any twinge of pain you’ve ever felt is the result, in part, of neurons in the brain and throughout your body sending chemical signals from one to the next. Now, Stanford scientists are a step closer to actually watching those signals as they take shape inside individual neurons — and watching lots of other previously hidden biological processes, too.
Their innovation: a new, finely crafted nanoparticle that lights up on command and lasts days, months or even longer: “Even the lifetime of a graduate student,” says Steven Chu, PhD, a professor of physics and of molecular and cellular physiology. Chu is the senior author of a new paper, published in Nature Photonics, on the development of the nanoparticles.
Biologists and others interested in tracking what’s going on with the molecules inside our cells have a few main choices, all of which involve attaching fluorescent tags to the molecules researchers are interested in. The first choice is fluorescent dyes or proteins, but those typically degrade after just a few seconds — not long enough to track biological processes like neuron signaling, says Qian Liu, PhD, a postdoctoral fellow in Chu’s lab and, along with fellow lab members Yunxiang Zhang and Sam Peng, a lead author on the new paper.
Another common choice is quantum dots, which last longer but come with an irritating problem: they blink on and off, making it tricky to track individual molecules over time.
Liu, Chu and colleagues’ solution was based on a third option, so-called upconversion nanoparticles, which don’t suffer the problems of dyes or quantum dots. Like the other methods, these nanoparticles light up brightly when an external light shines on them — the problem is, that external light needed to be so bright it could damage live cells. But by playing around with the structure and size of different layers of their nanoparticles, the team got a combination that would light up brightly even under fairly dim light.
Now, the scientists say, they are turning their attention to applications — and, first things first, tracking neurons’ molecular signals. Researchers know that those molecules are shuttled within neurons by two other proteins, called kinesin and dynein, but no one knows the details. Soon, and for the first time, researchers will be able to take prolonged videos of those molecules in action.
“It’s definitely new territory,” says Zhang.
The research was funded in part by the Stanford Neurosciences Institute as part of the first phase of its Big Ideas initiative, which aims to bring together researchers from across disciplines to better understand the brain.
Photo by N. Gupta, National Institute of Child Health and Human Development, NIH