11th April 2016

The first high-res 3D images of DNA segments

First-of-their-kind images by researchers at Berkeley Lab could aid in the use of DNA to build nanoscale devices.



Credit: Berkeley Lab

An international team working at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has captured the first high-resolution 3-D images from individual double-helix DNA segments, attached at either end of gold nanoparticles. The images detail the flexible structure of the DNA segments, which appear as nanoscale "jump ropes".

This unique imaging capability, pioneered by Berkeley Lab scientists, could aid in the use of DNA segments as building blocks for molecular devices that function as nanoscale drug-delivery systems, markers for biological research, and components for computer memory and electronic devices. It could also lead to images of disease-relevant proteins that have proven elusive for other imaging techniques, and of the assembly process that forms DNA from separate, individual strands.

The shapes of the coiled DNA strands, which were sandwiched between polygon-shaped gold nanoparticles, were reconstructed in 3-D using a cutting-edge electron microscope technique called individual-particle electron tomography (IPET). This was combined with a protein-staining process and sophisticated software that provided structural details down to a scale of just 2 nanometres (nm), or about two billionths of a metre.

"We had no idea about what the double-strand DNA would look like between the nanogold particles," said Gang Ren, a Berkeley Lab scientist who led the research. "This is the first time for directly visualising an individual double-strand DNA segment in 3-D."

While the 3-D reconstructions show the basic nanoscale structure of the samples, Ren said the next step will be to improve the resolution to the sub-nanometre scale: "Even in this current state, we begin to see 3-D structures at 1- to 2-nanometre resolution," he said. "Through better instrumentation and improved computational algorithms, it would be promising to push the resolution to that visualising a single DNA helix within an individual protein."

The technique, he said, has already excited interest among some prominent pharmaceutical companies and nanotechnology researchers, and his science team already has dozens of related research projects being planned. In future studies, they could attempt to improve the imaging resolution for complex structures that incorporate more DNA segments as a sort of "DNA origami," Ren said. Researchers hope to build and better characterise nanoscale molecular devices using DNA segments that can, for example, store and deliver drugs to targeted areas in the body.

"DNA is easy to program, synthesise and replicate, so it can be used as a special material to quickly self-assemble into nanostructures and to guide the operation of molecular-scale devices," he said. "Our current study is just a proof of concept for imaging these kinds of molecular devices' structures."

His team's work is published in the journal Nature Communications.



Berkeley Lab researchers Gang Ren (standing) and Lei Zhang. Photo by Roy Kaltschmidt/Berkeley Lab.

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