09 Dec Esq. Jon Cartu Writes – Advanced microscopy reveals unusual DNA structure »…
An advanced imaging technique reveals new structural details of S-DNA, ladder-like DNA that forms when the molecule experiences extreme tension. This work conducted at Sandia National Laboratories and Vrije University in the Netherlands provides the first experimental evidence that S-DNA contains highly tilted base pairs.
The predictable pairing and stacking of the DNA base pairs help to define the molecule’s double-helical shape. Understanding how the base pairs realign when DNA is stretched might provide insight into a range of biological processes and improve the design and performance of nanodevices built with DNA. Tilted base pairs in stretched S-DNA have been previously predicted using computer simulations, but never conclusively demonstrated in experiments until now, according to a recent article in Science Advances.
DNA is most commonly known as the molecular carrier of genetic information. However, in research labs around the world, it also has another use: construction material for nanoscale devices. To do this, scientists prepare computer-generated sequences of single-stranded DNA so that certain sections form base pairs with other sections. This forces the strand to bend and fold like origami. Researchers have used this principle to fold DNA into microscopic smiley faces, nanomachines with moving hinges and pistons and “smart” materials that spontaneously adjust to changes in the surrounding chemical environment.
“To build an airplane or a bridge, it’s important to know the structure, strength and stretchiness of every material that went into it,” said Adam Backer, an optical scientist at Sandia and lead author of the study. “The same thing is true when designing nanostructures with DNA.”
While much is known about the mechanical properties of DNA’s double helix, mysteries remain about the details of its shape when the molecule is stretched in a laboratory to form the ladder-like structure of S-DNA. Standard ways of visualizing DNA structure cannot track structural changes while the molecule untwists.
To characterize the structure and stretchiness of S-DNA, Backer worked with colleagues in the Physics of Living Systems research group at LaserLaB Amsterdam at Vrije University. The researchers described their process in the journal article. “This experiment provides the most direct evidence to date supporting the hypothesis that S-DNA contains tilted base pairs,” said Backer. “To gain this fundamentally new understanding of DNA, it was necessary to combine a number of cutting-edge technologies and bring scientists from a range of different technical disciplines together to work toward a common goal.”
There is widespread speculation among scientists that structures resembling S-DNA may form during the daily activities of human cells, but, at present, the biological purpose of S-DNA is still unknown. S-DNA might facilitate the repair of damaged or broken DNA, helping to guard against cell death and cancer. Backer hopes this clearer understanding of the physical principles governing DNA deformation will guide further research into the role of S-DNA in cells.
When Backer joined Sandia as a Truman Fellow in November 2016, he had the opportunity to start an independent research program of his own design. He had developed a method for polarization microscopy during graduate school at Stanford University and thought the technique had potential. Said Backer: “At Sandia I wanted to push this technique as far as it could go. The fact that this work has led to results with potential relevance to fields such as biology and nanotechnology has been extraordinary.”