How to view tiny parts of DNA? Make them ‘blink’

BOSTON, Mass. — A new technique can home in on parts of a cell that are smaller than 10 nanometers (billionths of a meter) in size without damaging the cell. On February 17, Vadim Backman described how he and his group makes cells do this. They take advantage of DNA’s natural ability to “blink” on when hit with the right color of light.

Backman and Hao Zhang work at Northwestern University in Evanston, Ill. Together, the biomedical engineers found a way to make some materials in a cell briefly shine more brightly than if they had been labeled with one of the most powerful fluorescent chemicals. Their trick: They tickle cells with a particular wavelength — or color — of light.

Backman presented the details, here, at the annual meeting of the American Association for the Advancement of Science. This new approach, he argues, can offer views of genetic material and other cellular parts that had been too small to see without dyes or techniques that might destroy them.

DNA and other proteins don’t naturally glow. So to make them show up in the darkness of a cell, scientists use special dyes that glow. They can attach a dye to the desired molecule in a cell, then flash some light on it. This will “excite” the dye, meaning the light will release some of its energy to the dye. Shortly afterward, the dye will fluoresce — releasing that energy again. But the light that the cell now gives off has a slightly different color. Taking a photo of this light can show biologists what was happening at that moment in a cell’s life cycle.

Backman and Zhang can now make cells glow much the same way — but without the dye. They still shine light on the cells. And if they use the right color, certain proteins inside the cell will become “excited.” Later, they too will blink on, emitting a brief, tell-tale glow.

The researchers call their new process SICLON. It’s short for a very long term: spectroscopic (SPEK-troh-SKOP-ik) intrinsic-contrast photon-localization optical nanoscopy (Naa-NOS-ko-pee).

So far, the engineers have used SICLON to peer at the inner walls of microtubules. These are structures that help separate chromosomes as a cell divides. Their technique has made it possible to resolve structures that are a mere 6.2 nanometers across. For comparison, a DNA molecule is around 3 nanometers wide. Backman says his group hopes their new blinking trick will make it possible to one day image how tiny inner structures change as a cell turns cancerous.