Scientists have captured the highest-resolution images ever taken of DNA, revealing previously unseen twisting and squirming behaviours.
Deoxyribonucleic acid, otherwise known as DNA, can be surprisingly active when crammed and contorted inside a cell, according to new research published in Nature Communications. These hidden movements were revealed by computer simulations fed with the highest-resolution images ever taken of a single molecule of DNA. The new study is exposing previously unseen behaviours in the self-replicating molecule, and this research could eventually lead to the development of powerful new genetic therapies.
“Seeing is believing, but with something as small as DNA, seeing the helical structure of the entire DNA molecule was extremely challenging,” Alice Pyne, the first author of the paper and a materials scientist at the University of Sheffield, said in a statement from the university. “The videos we have developed enable us to observe DNA twisting in a level of detail that has never been seen before.”
Scientists have previously used microscopes to gaze upon DNA and its twisted ladder-like configuration, but these were limited to static views of the molecule. What scientists haven’t been able to see is how the intense coiling of DNA affects its double-helical structure. To accomplish this, Pyne and her colleagues combined high-resolution atomic force microscopy (AFM) with molecular dynamics computer simulations, which revealed the writhing.
Long, highly organised strands of DNA are crammed tightly inside our cells. As the new study shows, this results in some surprisingly dynamic physical behaviours.
Agnes Noy, a lecturer at the University of York and a co-author of the study, said the microscopy images and the computer simulations agreed so well that they boosted the resolution of their experiments, allowing the team to “track how each atom of the double helix of DNA dances.”
For the study, the researchers analysed DNA minicircles, in which a small strand is joined at both ends, forming a loop structure. DNA minicircles have been described before, and they’re believed to be important indicators of health.
Microscopic images of DNA minicircles in their “relaxed” position (i.e. no twists) revealed very little movement, but extra twists brought the loop to life, resulting in more vigorous movements. These dynamic moves may serve an important purpose, helping the DNA to find binding partners and facilitate growth.
The new atomic force microscopy shows, “with remarkable detail,” how “wrinkled, bubbled, kinked, denatured, and strangely shaped” the DNA minicircles really are, “which we hope to be able to control someday,” Baylor College of Medicine biologist Lynn Zechiedrich, who supplied the minicircles for the study, said in the University of Sheffield statement.
Indeed, further insights into DNA, and how it’s able to get so compact, could lead to the development of completely new medical interventions, including improved DNA-based diagnostics and therapeutics, according to the researchers.