(l-r) Thomas Gerling, Andrea Neuner, Klaus Wagenbauer, and Prof. Hendrik Dietz. (Photo: U. Benz / TUM)
(l-r) Thomas Gerling, Andrea Neuner, Klaus Wagenbauer, and Prof. Hendrik Dietz. (Photo: U. Benz / TUM)

Arm-waving nanorobot signals new flexibility in DNA origamiDesigner's toolkit for dynamic DNA nanomachines

The latest DNA nanodevices created at the Technische Universität München (TUM) – including a robot with movable arms, a book that opens and closes, a switchable gear, and an actuator – may be intriguing in their own right, but that's not the point. They demonstrate a breakthrough in the science of using DNA as a programmable building material for nanometer-scale structures and machines. Results published in the journal Science reveal a new approach to joining – and reconfiguring – modular 3D building units, by snapping together complementary shapes instead of zipping together strings of base pairs. This not only opens the way for practical nanomachines with moving parts, but also offers a toolkit that makes it easier to program their self-assembly.

The field popularly known as "DNA origami," in reference to the traditional Japanese art of paper folding, is advancing quickly toward practical applications, according to TUM Prof. Hendrik Dietz. Earlier this month, Dietz was awarded Germany's most important research award, the Gottfried Wilhelm Leibniz Prize, for his role in this progress.

In recent years, Dietz and his team have been responsible for major steps in the direction of applications:  experimental devices including a synthetic membrane channel made from DNA; discoveries that cut the time needed for self-assembly processes from a week to a few hours and enable yields approaching 100%; proof that extremely complex structures can be assembled, as designed, with subnanometer precision.

Yet all those advances employed "base-pairing" to determine how individual strands and assemblies of DNA would join up with others in solution. What's new is the "glue."

"Once you build a unit with base pairs," Dietz explains, "it's hard to break apart. So dynamic structures made using that approach tended to be structurally simple." To enable a wider range of DNA nanomachines with moving parts and potentially useful capabilities, the team adapted two more techniques from nature's biomolecular toolkit: the way proteins use shape complementarity to simplify docking with other molecules, and their tendency to form relatively weak bonds that can be readily broken when no longer needed.

Bio-inspired flexibility

For the experiments reported in Science, Dietz and his co-authors – doctoral candidates Thomas Gerling and Klaus Wagenbauer, and bachelor's student Andrea Neuner from TUM's Munich School of Engineering – took inspiration from a mechanism that allows nucleic acid molecules to bond through interactions weaker than base-pairing. In nature, weak bonds can be formed when the RNA-based enzyme RNase P "recognizes" so-called transfer RNA; the molecules are guided into close enough range, like docking spacecraft, by their complementary shapes.

The new technology from Dietz's lab imitates this approach. To create a dynamic DNA nanomachine, the researchers begin by programming the self-assembly of 3D building blocks that are shaped to fit together. A weak, short-ranged binding mechanism called nucleobase stacking can then be activated to snap these units in place. Three different methods are available to control the shape and action of devices made in this way.

"What this has given us is a tiered hierarchy of interaction strengths," Dietz says, "and the ability to position – precisely where we need them – stable domains that can recognize and interact with binding partners." The team produced a series of DNA devices – ranging from micrometer-scale filaments that might prefigure technological "flagella" to nanoscale machines with moving parts – to demonstrate the possibilities and begin testing the limits.

For example, transmission electron micrographs of a three-dimensional, nanoscale humanoid robot confirm that the pieces fit together exactly as designed. In addition, they show how a simple control method – changing the concentration of positive ions in solution – can actively switch between different configurations:  assembled or disassembled, with "arms" open wide or resting at the robot's side.

Another method for switching a DNA nanodevice between its different structural states – by simply raising and lowering the temperature – proved to be especially robust. For earlier generations of devices, this required separating and re-joining DNA base pairs, and thus the systems were "worn out" by dilution and side-reactions after just a few cycles of switching. A scissor-like actuator described in the current paper underwent more than a thousand temperature-switched cycles over a four-day period with no signs of degradation.

"Temperature cycling is a way to put energy into the system," Dietz adds, "so if the reversible conformational transition could be coupled to some continously evolving process, we basically now have a way not just to build nanomachines, but also to power them."

"A snap" – like child's play

There is yet another dimension to the flexibility gained by adding shape-complementary components and weak bonding to the DNA nanotechnology toolkit. Programming self-assembly by base-pairing alone is like writing computer code in machine language. The hope is that this new approach will make it easier to bend DNA origami toward practical ends, in much the same way the advent of higher-level computer programming languages spurred advances in software engineering.

Dietz compares it to building with children's toys like LEGO: "You design the components to be complementary, and that's it. No more fiddling with base-pair sequences to connect components.

This research was supported by the German Research Foundation (DFG) through the Excellence Clusters CIPSM and NIM, the Collaborative Research Center SFB863, the TUM Institute for Advanced Study, the TUM International Graduate School of Science and Engineering, and the Munich School of Engineering; the European Research Council (ERC Starting Grant); and the Hans L. Merkle Foundation.


Dynamic DNA devices and assemblies formed by shape-complementary, non-base pairing 3D components. Thomas Gerling, Klaus F. Wagenbauer, Andrea M. Neuner, and Hendrik Dietz. Science, 27 March, 2015. doi/10.1126/science.aaa5372

Prof. Hendrik Dietz
Technische Universität München
TUM Laboratory for Biomolecular Nanotechnology
Tel.:+49 (0) 89 289-11615

Technical University of Munich

Corporate Communications Center Patrick Regan

Article at tum.de

A research team at TUM has developed hollow nano-objects made of DNA material that bind viruses tightly and thus render them harmless.

The virus trap

To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses...

Elektrische Felder steuern den rotierenden Nano-Kran – 100.000 mal schneller als bisherige Methoden. (Bild: Enzo Kopperger / TUM)

Piecework at the nano assembly line

Scientists at the Technical University of Munich (TUM) have developed a novel electric propulsion technology for nanorobots. It allows molecular machines to move a hundred thousand times faster than with the biochemical...

Doppelsträngige DNA kann mithilfe von Proteinen in dreimdimensionale Formen gefaltet werden. (Bild: Ella Maru Studio & Dietz Lab / TUM)

Designer proteins fold DNA

Florian Praetorius and Prof. Hendrik Dietz of the Technical University of Munich (TUM) have developed a new method that can be used to construct custom hybrid structures using DNA and proteins. The method opens new...

Die Pinzetten-Struktur besteht aus zwei starren DNA-Balken, die durch ein Gelenk verbunden sind.

In the molecular bench vise

The genome molecule contains the blueprint for life. The manner in which the blueprint is packed into the cell determines which genes are active and which are set to inactive. Disturbing this structure can result in...

TUM-Vizepräsident Hofmann (l) überreicht Prof. Feringa die Ernennungsurkunde zum Honorary Hans Fischer Senior Fellow des TUM-IAS - Bild: Astrid Eckert / TUM

Nobel Prize goes to TUM IAS Fellow Prof. Bernard L. Feringa

Prof. Jean-Pierre Sauvage, Prof. Sir J. Fraser Stoddart and Prof. Bernard L. Feringa have received this year's Nobel Prize in Chemistry for their groundbreaking work on the design and production of molecular machines. Prof....

Illustration der Basenpaar-Stapelwechselwirkungen.

Measuring forces in the DNA molecule

DNA, our genetic material, normally has the structure of a twisted rope ladder. Experts call this structure a double helix. Among other things, it is stabilized by stacking forces between base pairs. Scientists at the...

DNA-Nanogreifer. Dietz Lab/TUM

Nanoscale rotor and gripper push DNA origami to new limits

Scientists at the Technical University of Munich (TUM) have built two new nanoscale machines with moving parts, using DNA as a programmable, self-assembling construction material. In the journal Science Advances, they...

Prof. Dr. Hendrik Dietz erhält den Leibniz-Preis 2015. (Foto: A. Eckert und A. Heddergott / TU München)

Fourth Leibniz prizewinner in the TUM Physics Department

Prof. Dr. Hendrik Dietz from the Technische Universität München (TUM) has been awarded the Gottfried Wilhelm Leibniz Prize of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). The 36-year-old...

3D Visualisierung von Versuchsdaten

Reality check for DNA nanotechnology

Two major barriers to the advancement of DNA nanotechnology beyond the research lab have been knocked down. This emerging technology employs DNA as a programmable building material for self-assembled, nanometer-scale...

Researchers build synthetic membrane channels out of DNA

As reported in the journal Science, physicists at the Technische Universität München (TUM) and the University of Michigan have shown that synthetic membrane channels can be constructed through "DNA nanotechnology." This...