For years, textbooks have been preaching that macromolecules within living cells, such as DNA, RNA, and proteins, do not absorb light and fluoresce—at least on their own. But a team from Northwestern University's McCormick School of Engineering is about to debunk that belief. 

Fluorescence is the emission of light by a substance that has absorbed either light or some kind of electromagnetic radiation. In life sciences, this form of luminescence is used as a way to track or analyze biological molecules without destroying them. Now, some proteins or small molecules in cells are naturally fluorescent, but it is typical for researchers to rely on special fluorescence dyes when imaging macromolecules to enhance contrast. 

But using artificial dyes may soon be a thing of the past.  


Auto-fluorescence of an individual chromosome. Credit: Northwestern

Northwestern Professors Vadim Backman, Hao Zhang, and Cheng Sun have caught DNA doing something it has never been seen doing before: It blinked. 

In their research published in the Proceedings of the National Academy of Sciences, the team described how they discovered the macromolecules getting excited and lighting up when illuminated with visible light. In fact, the molecules lit up better than they would have if a powerful fluorescent label was used. 

So why has no one spotted the fluorescence before? That's because the molecules spend much of their time in the "dark state," a condition in which they neither absorb nor emit light, according to Backman. He likened the situation to athletic interval training, where runners, for example, alternate running very, very fast and resting. 

"You might catch them when they are resting and assume they aren’t doing anything. That's what DNA and proteins do. They fluoresce for a very short time and then rest for a very long time," he said. 

This discovery could pave the way for label-free, super-resolution nanoscopic imaging—one that is free of toxic staining that makes it tricky for researchers to get an active image of living cells. This could go well with the improved DNA imaging technique that can examine DNA strands at the nanoscale. 

"This is ideal because staining is toxic," Zhang said, "and it makes imaging less precise." 

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