Hendrik Dietz: Making tiny components with DNA

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Hendrik Dietz says that he has a strongly visual imagination – useful for designing amino acid-based nanostructures. Quelle: Heddergott / TUM

22.02.2010  - 

“It is as if the DNA had learnt yoga,” commented impressed US colleagues on the discovery in which Hendrik Dietz was significantly involved. During his two-year stay at Harvard Medical School, together with William Shih he succeeded in creating a collection of nanoscale component parts using DNA fragments. Experts in the field were astounded, and on account of his achievements, in June 2009 Dietz was named Professor of Experimental Biophysics at the Technical University Munich - aged just 31.

Perhaps it’s good that Hendrik Dietz first studied physics before dedicating himself to biology. The quantum of strangeness from the physics world, and this outsider’s perspective has helped him become a shooting star in the world of biophysics. The scientific community is electrified by his work, although he refers to it with a touch of irony as “handicraft and knitting on a nanoscale.” In just two years, working alongside Harvard colleagues William M. Shih, and Shawn M. Douglas, he succeeded in manufacturing all manner of forms using just DNA - deoxyribonucleic acid, from which our genes are constructed. Among these were tiny bricks, balls, gears, straight and curved bands, and others, including many extremely complex structures. What at first seemed like a gimmick has since become a recognised and automated manufacturing procedure for nanostructures.

Using pincer molecules and targeted insertions of base pairs, Hendrik Dietz encourages the DNA to bend to his will into tiny components. Source: HD/SMD

Gauging the protein world

Born in 1977 in Dresden, Dietz studied physics in Paderborn and in Saragossa, Spain. He is familiar with the Technical University of Munich since the time of his dissertation at the Department of Applied Physics under Professor Hermann Gaub. “What fascinates me is the complexity of the processes in a cell,” says Dietz. “About 4000 to 5000 proteins work together, each performing its task, and all of these tasks are interconnected. To explore how this functions was a challenge that I found immediately exciting.” So, Dietz applied a procedure that was still quite fresh: examining protein molecules using an atomic force microscope (or scanning force microscope). This uses an extremely fine tip that can exert and measure forces on an atomic level.

Hendrik Dietz’ supervisor Matthias Rief had already used the microscope to stretch a chain-like muscle protein. Dietz decided to pursue a different path. “Proteins are three-dimensional structures, and if you pull them apart, all the information contained in the spatial folding is lost,” he explains. He developed a method that enabled him to bundle the tiny parts into wholes at extremely different points in their structures, and to pull them into different directions. This approach preserves the folding, and the subsequently measured forces provide information on the internal structure, stability and elasticity of the molecules.

Amino acid tools

Dietz caught a glimpse of something after completing his doctoral degree - and he is still pursuing this goal today: using the components of proteins - amino acids - to construct tiny tools, which in turn are able to produce substances. However, working with proteins on this scale is extremely difficult; they are too complex in form and function. Dietz thus looked for another route that would enable him to build the imagined nanotools. DNA provided the key. Their molecules are chain-like, regular and stable and, above all, very well researched.

As far back as 1991, researchers Junghuei Chen and Nadrian C. Seeman had created tiny cubes of DNA. This marked the beginning of a new field of science; they were the first to show that you can build with DNA. There followed a series of small advances, “but 2006 really was a revolution,” says Dietz. In that year, Paul W. K. Rothemund from Caltech in California succeeded in producing complex shapes using DNA. He named his method origami after the Japanese art of paper folding, and demonstrated them in nanoscale with smiley faces and a map of North and South America. The disadvantage of these objects, however, is that they are two-dimensional, i.e. a flat pattern on an underlay.

A puzzle that completes itself

At some point, Hendrik Dietz learned during a symposium that William Shih at the Harvard Medical School was seeking to create three-dimensional objects using DNA, and in 2007 he joined Shih’s research group. Together with the computer scientist Shawn Douglas, over the next two years the scientists pulled off a coup. They “stapled” together single-stranded DNA produced by viruses, which they called the “backbone”, with tiny, artificially produced DNA snippets, so-called “pincer molecules”, thereby following a preprogrammed process. The miracle takes place in a test tube: “You combine all the required parts, heat them up, stir, and see what comes out,” says Dietz.

With his method of combining DNA strands with pincer molecules at specific points, Hendrik Dietz initially managed to create essentially straight structures, such as rectangles or blocks. Source: Hendrik Dietz / TUM

Like a puzzle that can complete itself, the small objects emerged as a result of self-organisation – millions at a time. Scientists could identify the form under an electron microscope, and check if the process had been successful. Over time, the researchers became more experienced in handling their building materials. It was soon possible to systematize the rules for the DNA assembling, and to save them as computer programs. “We now have a set of rules that can be used to program the smallest DNA building blocks. You can combine them at will, like Lego blocks,” says Dietz. In the meantime, it is even possible to bend and twist the DNA.

Pretzel-shaped DNA

There’s been a great deal of interest in the physicist since Dietz and his colleagues published their findings in Nature in May 2009 and in Science in August 2009. Even the New York Times reported on their work, and the American news network MSNBC featured the invention in an article called “DNA twisted into pretzels”. His peers are also full of praise: Thomas H. LaBean at Duke University in North Carolina, commenting euphorically on the article in Nature, said  “it’s a third revolution in DNA nanotechnology,” and “it opens up a new dimension in the art of DNA.” Scientists Yan Liu and Hao Yan at Arizona State University were equally enthusiastic in Science: “It is as if the DNA had learnt yoga to adopt a variety of different positions on the nanoscale.”

Dietz decided to go back to Germany because he wanted to start his own research group, and not work exclusively on other people’s ideas. The offer from the Technical University of Munich came at just the right time. In June 2009, he accepted the Chair of Experimental Physics in Munich and is now the youngest professor of the TU Physics Department. In addition to practical applications for his nano-objects, such as microscopy or basic research, he has continued to pursue his goal of imitating nature, or perhaps even improving on it a little. For example, he is hoping to construct proteins that perform specific tasks within cells, such as open and close pores in the cell membrane, or produce chemicals by compacting reaction components into the right shape at the atomic level, forcing them to react. Recreating natural proteins one by one is not a good solution, thinks Dietz. “These molecules carry evolutionary ballast with them, parts that are possibly not necessary for their functioning. This can perhaps be better achieved with a synthetic approach.” Being able to implement these kinds of revolutionary ideas has bolstered Dietz’s reputation as a creative scientist, and has brought a great deal of attention to his highly regarded publications. He’s able to propose “crazy” ideas that might be ridiculed in other circumstances. Nevertheless, there’s room for self-doubt: “I could still fail resoundingly...”

Author: Brigitte Röthlein

Extract from Issue 5 of “Faszination Forschung”, the scientific journal of the Technical University of Munich