DNA-Origami Nanoengine Performing Pulsing Movements

An international team of scientists has just invented a revolutionary form of DNA nano-engine. It is powered by a smart mechanism and can execute pulsing motions. The researchers intend to attach a coupling to it and use it as a motor in complicated nanomachines. Their findings were published in the journal Nature Nanotechnology on October 19^th, 2023.

Petr Šulc, an assistant professor at the School of Molecular Sciences at Arizona State University and the Biodesign Center for Molecular Design and Biomimetics, has worked on this project with Professors Nils Walter from the University of Michigan and Michael Famulok (the project lead) from the University of Bonn, Germany.

Utilizing the computer modeling tools available to his group, Šulc has gained insight into the construction and functioning of this leaf-spring nano-engine. Nearly 14,000 nucleotides make up the structure; they are the fundamental building blocks of DNA.

Being able to simulate motion in such a large nanostructure would be impossible without oxDNA, the computer model that our group uses for design and design of DNA nanostructures. It is the first time that a chemically powered DNA nanotechnology motor has been successfully engineered. We are very excited that our research methods could help with studying it, and are looking forward to building even more complex nanodevices in the future.”

Petr Šulc, Assistant Professor, School of Molecular Sciences, Arizona State University

When used often, this innovative type of engine could improve the grip, much like a hand grip strength trainer. The motor is about a million times smaller, though. A spring connects two handles in a V-shaped design.

In a hand grip strength trainer, you squeeze the handles together against the resistance of the spring. Once you release your grip, the spring pushes the handles back to their original position.

Our motor uses a very similar principle. But the handles are not pressed together but rather pulled together.”

Michael Famulok, Project Lead and Professor, University of Bonn

The system that keeps plants and animals alive on Earth has been repurposed by the researchers. Each cell has its own little library. It includes the instructions for every type of protein that a cell needs to operate. The cell orders a copy of the relevant blueprint if it wants to manufacture a specific type of protein. The RNA polymerases are the enzymes responsible for producing this transcript.

RNA Polymerases Drive the Pulsing Movements

The original DNA blueprint is made up of lengthy strands. Letter by letter, the recorded information is replicated by the RNA polymerases as they travel along these strands.

Famulok added, “We took an RNA polymerase and attached it to one of the handles in our nanomachine. In close proximity, we also strained a DNA strand between the two handles. The polymerase grabs on to this strand to copy it. It pulls itself along the strand and the nontranscribed section becomes increasingly smaller. This pulls the second handle bit by bit towards the first one, compressing the spring at the same time.”

Just before its conclusion, a certain letter sequence can be found in the DNA strand that runs between the handles. The polymerase receives a signal from this so-called termination sequence instructing it to release the DNA.

The handles can then be moved apart by the spring, relaxing once more. As a result, the strand’s start sequence approaches the polymerase, allowing the molecular copy to initiate a fresh transcription cycle. Next, the cycle is repeated.

In this way, our nanomotor performs a pulsing action.”

Mathias Centola, Ph.D. Student. University of Bonn

An Alphabet Soup Serves as Fuel

Like any other motor, this one requires energy as well. The “alphabet soup,” from which the polymerase generates the transcripts, supplies it. Each of these letters—referred to as nucleotides in technical parlance—has a short tail made up of three phosphate groups, or triphosphates.

The polymerase must eliminate two of these phosphate groups to append a new letter to an already-existing phrase. This lets go of energy that it can utilize to connect the letters.

“Our motor thus uses nucleotide triphosphates as fuel. It can only continue to run when a sufficient number of them are available,” Famulok stated.

The motor’s ease of integration with various structures was shown by the researchers. This should enable it to do things like meander across a surface, akin to an inchworm pulling itself along a limb in a distinctive manner.

Famulok added, “We are also planning to produce a type of clutch that will allow us to only utilize the power of the motor at certain times and otherwise leave it to idle.”

Eventually, the motor could act as the central nervous system of an intricate nanomachine.

“However, there is still a lot of work to be done before we reach this stage,” Famulok further noted.

The extremely multidisciplinary lab of Šulc combines statistical physics and computer modeling techniques to a wide range of challenges in biology, chemistry, and nanotechnology. The group creates novel multiscale models to investigate the relationships between biomolecules, especially concerning the modeling and design of devices and nanostructures made of DNA and RNA.

He stated, “Just as complex machines in our everyday use—planes, cars and chips in electronics—require sophisticated computer-aided design tools to make sure they perform a desired function, there is a pressing need to have access to such methods in the molecular sciences.”

Professor Tijana Rajh, director of the School of Molecular Sciences, stated, “Petr Šulc and his group are doing extremely innovative molecular science, using the methods of computational chemistry and physics to study DNA and RNA molecules in the context of biology as well as nanotechnology. Our younger faculty members in the School of Molecular Sciences have an extraordinary record of achievement, and Professor Šulc is an exemplar in this regard.”

Advances in Bionanotechnology to Continue

The two fundamental molecules of life are DNA and RNA. They perform a variety of tasks in living cells, such as information transport and storage. Additionally, they have exciting potential uses in the realm of nanotechnology, where devices and structures at the nanoscale are assembled using engineered DNA and RNA strands.

“It is a little bit like playing with Lego blocks except that each Lego block is only a few nanometers (a millionth of a millimeter) in size, and instead of putting each block into the place where it should go, you put them inside a box and shake it randomly until only the desired structure comes out,” Šulc added.

He concluded, “The promising applications of this field include diagnostics, therapeutics, molecular robotics and building of new materials. My lab has developed the software to design these blocks, and we work closely with experimental groups at ASU as well as other universities in the US and Europe. It is exciting seeing our methods used to design and characterize nanostructures of increasing complexity, as the field progresses and we achieve new advanced designs and successfully operate them at nanoscale.”