An electron microscope image of a CdS quantum dot made with ConK. Image courtesy of the Hecht and Scholes labs.Nature uses 20 canonical amino acids as building blocks to make proteins, combining their sequences to create complex molecules that perform biological functions.
But what happens with the sequences not selected by nature? And what possibilities lie in constructing entirely new sequences to make novel, or de novo, proteins bearing little resemblance to anything in nature? That’s the terrain that researchers in Princeton University’s Hecht Lab work in. And recently, their curiosity for designing their own sequences paid off.
They have discovered the first known de novo protein that catalyzes, or drives, the synthesis of quantum dots, which are fluorescent nanocrystals used in electronic applications from LED screens to solar panels. Their work, reported in a paper in the Proceedings of the National Academy of Sciences, opens the door to making nanomaterials in a more sustainable way by demonstrating that protein sequences not derived from nature can be used to synthesize functional materials – with pronounced benefits for the environment.
Quantum dots are normally made in industrial settings with high temperatures and toxic, expensive solvents – a process that is neither economical nor environmentally friendly. But the Hecht Lab researchers managed to pull off this process at the bench using water as a solvent, making a stable end-product at room temperature.
“We’re interested in making life molecules, proteins, that did not arise in life,” said Michael Hecht, a professor of chemistry at Princeton University, who led the research with Greg Scholes, also a professor of chemistry and chair of the department. “In some ways we’re asking, are there alternatives to life as we know it? All life on Earth arose from common ancestry. But if we make lifelike molecules that did not arise from common ancestry, can they do cool stuff?
“So here, we’re making novel proteins that never arose in life doing things that don’t exist in life.”
The team’s process can also tune the size of the nanoparticles, which determines the color that the quantum dots glow, or fluoresce, in. That holds possibilities for tagging molecules within a biological system, like staining cancer cells in vivo.
“Quantum dots have very interesting optical properties due to their sizes,” said Yueyu Yao, a fifth-year graduate student in the Hecht Lab and a co-author of the paper. “They’re very good at absorbing light and converting it to chemical energy – that makes them useful for being made into solar panels or any sort of photosensor.
“But, on the other hand, they’re also very good at emitting light at a certain desired wavelength, which makes them suitable for making LED screens.”
And because they’re small – comprised of only about 100 atoms and maybe 2nm across – they’re able to penetrate some biological barriers, making their utility in medicine and biological imaging especially promising.
“I think using de novo proteins opens up a way for designability,” said Leah Spangler, a former postdoc in the Scholes Lab and lead author of the paper. “A key word for me is ‘engineering’. I want to be able to engineer proteins to do something specific, and this is a type of protein you can do that with.
“The quantum dots we’re making aren’t great quality yet, but that can be improved by tuning the synthesis. We can achieve better quality by engineering the protein to influence quantum dot formation in different ways.”
Based on work done by Sarangan Chari, a senior chemist in the Hecht Lab and a corresponding author of the paper, the team used a de novo protein it designed named ConK to catalyze the quantum dot reaction. The researchers first isolated ConK in 2016 from a large combinatorial library of proteins. It’s still made of natural amino acids, but it qualifies as de novo because its sequence doesn’t have any similarity to a natural protein.
The researchers found that ConK allowed Escherichia coli cells to survive in otherwise toxic concentrations of copper, suggesting it might be useful for metal binding and sequestration. The quantum dots used in this research are made of cadmium sulfide (CdS). As cadmium is a metal, the researchers wondered whether ConK could be used to synthesize these quantum dots.
Their hunch paid off. They found that ConK can break down cysteine, one of the 20 amino acids, into several products, including hydrogen sulfide. This acts as the active sulfur source that can then go on to react with the metal cadmium to produce CdS quantum dots.
“To make a cadmium sulfide quantum dot, you need the cadmium source and the sulfur source to react in solution,” said Spangler. “What the protein does is make the sulfur source slowly over time. So, we add the cadmium initially, but the protein generates the sulfur, which then reacts to make distinct sizes of quantum dots.”
This story is adapted from material from Princeton University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.