New DNA Imaging Method Unveils Strands At Nanoscale

A new DNA imaging method developed by scientists has given researchers a deeper view into individual DNA strands than ever before. The new view is so good, in fact, that the new imaging methods can now make DNA strands visible on the nanoscale. Presumably, the new imaging method could allow scientists to understand how damaged DNA impacts diseases and other genetic or cellular processes.

The new DNA imaging method is actually not new; it’s an advancement/continuation of earlier imaging technology. The technology is called “single-molecule microscopy,” and the new DNA imaging method enhances it via added information pertaining to the movement and orientation of specialized fluorescent dyes, which are attached to individual strands of DNA prior to the magnification process, reports Phys.

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Single-molecule spectroscopy was developed at Stanford University back in 1989, and ever since it has been utilized by the scientific community for visualizing individual molecules using optical microscopy; prior to that time, it had been impossible.

“Of the 2014 Nobel Laureates for optical microscopy beyond the diffraction limit (Moerner, Hell & Betzig), Moerner and Betzig used single molecules to image a dense array of molecules at different times.”

In Optica, a team of researchers led by Moerner explains how the new technique works to help create ultra-HD images and orientations for literally thousands of infinitesimally tiny individual fluorescent dye molecules attached to strands of DNA in the new imaging method.

“You can think of these new measurements as providing little double-headed arrows that show the orientation of the molecules attached along the DNA strand,” said Moerner. “This orientation information reports on the local structure of the DNA bases because they constrain the molecule. If we didn’t have this orientation information the image would just be a spot.”

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DNA strands are very long and also very narrow, with a width of only a few nanometers. Using the new DNA imaging methods, the “string” of DNA can now been seen more clearly. Prior to the new imaging technology, it was completely impossible to discern how the dyes were oriented or how they were attacked to the DNA strands.

Essentially, the new DNA imaging method allows researchers to get a much better overall view of the DNA, and can give scientists a better understanding of each molecule of dye.

“Our new imaging technique examines how each individual dye molecule labeling the DNA is aligned relative to the much larger structure of DNA.”

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The new DNA imaging method gives scientists a more detailed view of the DNA than prior methods, and it’s also much faster. It can even be used for so-called “dim molecules,” which were problematic using older DNA imaging methods.

Scientists are hopeful that, due to the nanoscale visibility of the DNA using the new technique, they may be able to monitor changes to the conformation of DNA or damages to individual regions of DNA strands, both of which were impossible before. It’s even possible that the new DNA imaging method could be utilized to observe and monitor the basis of many processes at the cellular level, namely interaction between proteins and DNA itself.

In a single imaging experiment, scientists using the new DNA imaging method were able to observe 30,000 single-molecule orientations in under 15 minutes.

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The new DNA imaging method works by adding an electro-optic modulator to a commonly used, tried-and-true single-molecule microscope. The additional device changes the polarization of the laser light in each camera frame. This technique allowed scientists to determine the orientation and rotational dynamics on a frame-by-frame basis.

“If someone has a single-molecule microscope, they can perform our technique pretty easily by adding the electro-optic modulator. We’ve used fairly standard tools in a slightly different way and analyzed the data in a new way to gain additional biological and physical insight.”

In layman’s terms, this new DNA imaging method provides much more precise imaging in less time and with relatively little needed in terms of equipment upgrades.

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