Nanotechnology Now

Our NanoNews Digest Sponsors
Heifer International



Home > Press > DNA nanotechnology places enzyme catalysis within an arm's length

Abstract:
Using molecules of DNA like an architectural scaffold, Arizona State University scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway that could prove important for future biomedical and energy applications.

DNA nanotechnology places enzyme catalysis within an arm's length

Tempe, AZ | Posted on May 25th, 2014

The findings were published in the journal Nature Nanotechnology. Led by ASU Professor Hao Yan, the research team included ASU Biodesign Institute researchers Jinglin Fu, Yuhe Yang, Minghui Liu, Professor Yan Liu and Professor Neal Woodbury along with colleagues Professor Nils Walter and postdoctoral fellow Alexander Johnson-Buck at the University of Michigan.

Researchers in the field of DNA nanotechnology, taking advantage of the binding properties of the chemical building blocks of DNA, twist and self-assemble DNA into ever-more imaginative 2- and 3-dimensional structures for medical, electronic and energy applications.

In the latest breakthrough, the research team took up the challenge of mimicking enzymes outside the friendly confines of the cell. These enzymes speed up chemical reactions, used in our bodies for the digestion of food into sugars and energy during human metabolism, for example.

"We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level," Yan said, who holds the Milton Glick Chair in the ASU Department of Chemistry and Biochemistry and directs the Center for Molecular Design and Biomimicry at the Biodesign Institute.

With enzymes, all moving parts must be tightly controlled and coordinated, otherwise the reaction will not work. The moving parts, which include molecules such as substrates and cofactors, all fit into a complex enzyme pocket just like a baseball into a glove. Once all the chemical parts have found their place in the pocket, the energetics that control the reaction become favorable, and swiftly make chemistry happen. Each enzyme releases its product, like a baton handed off in a relay race, to another enzyme to carry out the next step in a biochemical pathway in the human body.

For the new study, the researchers chose a pair of universal enzymes, glucose-6 phosphate dehydrogenase (G6pDH) and malate dehydrogenase (MDH), that are important for biosynthesis—making the amino acids, fats and nucleic acids essential for all life. For example, defects found in the pathway cause anemia in humans. "Dehydrogenase enzymes are particularly important since they supply most of the energy of a cell", said Walter. "Work with these enzymes could lead to future applications in green energy production such as fuel cells using biomaterials for fuel."

In the pathway, G6pDH uses the glucose sugar substrate and a cofactor called NAD to strip hydrogen atoms from glucose and transfer to the next enzyme, MDH, to go on and make malic acid and generate NADH in the process, which is used for as a key cofactor for biosynthesis.

Remaking this enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology.

To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes.

In the middle of the DNA scaffold, they affixed a single strand of DNA, with the NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes.

Once the system was made in a test tube by heating up and cooling the DNA, which leads to self-assembly, the enzyme parts were added in. They confirmed the structure using a high-powered microscope, called an AFM, which can see down to the nanoscale, 1,000 times smaller than the width of a human hair.

Like architects, the scientists first built a full-scale model so they could test and measure the spatial geometry and structures, including in their setup a tiny fluorescent dye attached to the swinging arm. If the reaction takes place, they can measure a red beacon signal that the dye gives off---but in this case, unlike a traffic signal, a red light means the reaction works.

Next, they tried the enzyme system and found that it worked just the same as a cellular enzyme cascade. They also measured the effect when varying the distance between the swinging arm and the enzymes. They found there was a sweet spot, at 7nm, where the arm angle was parallel to the enzyme pair.

With a single swinging arm in the test tube system working just like the cellular enzymes, they decided to add arms, testing the limits of the system with up to 4 added arms. They were able to show that as each arm was added, the G6pDH could keep up to make even more product, while the MDH had maxed out after only two swinging arms. "Lining enzymes up along a designed assembly line like Henry Ford did for auto parts is particularly satisfying for someone living near the motor city Detroit," said Walter.

The work also opens a bright future where biochemical pathways can be replicated outside the cell to develop biomedical applications such as detection methods for diagnostic platforms.

"An even loftier and more valuable goal is to engineer highly programmed cascading enzyme pathways on DNA nanostructure platforms with control of input and output sequences. Achieving this goal would not only allow researchers to mimic the elegant enzyme cascades found in nature and attempt to understand their underlying mechanisms of action, but would facilitate the construction of artificial cascades that do not exist in nature," said Yan.

###

The research is supported by a Multi-disciplinary University Research Initiative (MURI) grant from Army Research Office, with the goal of translating biochemical pathways into non-cellular environments.

####

About Arizona State University
Remaking an artificial enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology.

To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes.

In the middle of the DNA scaffold, they affixed a single strand of DNA, with the NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes.

Credit: Jason Drees, The Biodesign Institute at ASU

For more information, please click here

Contacts:
Joe Caspermeyer

480-258-8972

Copyright © Arizona State University

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related Links

Video:

Related News Press

News and information

New method in the fight against forever chemicals September 13th, 2024

Energy transmission in quantum field theory requires information September 13th, 2024

Breakthrough in proton barrier films using pore-free graphene oxide: Kumamoto University researchers achieve new milestone in advanced coating technologies September 13th, 2024

Quantum researchers cause controlled ‘wobble’ in the nucleus of a single atom September 13th, 2024

Govt.-Legislation/Regulation/Funding/Policy

Giving batteries a longer life with the Advanced Photon Source: New research uncovers a hydrogen-centered mechanism that triggers degradation in the lithium-ion batteries that power electric vehicles September 13th, 2024

New discovery aims to improve the design of microelectronic devices September 13th, 2024

Physicists unlock the secret of elusive quantum negative entanglement entropy using simple classical hardware August 16th, 2024

Single atoms show their true color July 5th, 2024

Chip Technology

New discovery aims to improve the design of microelectronic devices September 13th, 2024

Groundbreaking precision in single-molecule optoelectronics August 16th, 2024

Enhancing electron transfer for highly efficient upconversion: OLEDs Researchers elucidate the mechanisms of electron transfer in upconversion organic light-emitting diodes, resulting in improved efficiency August 16th, 2024

Physicists unlock the secret of elusive quantum negative entanglement entropy using simple classical hardware August 16th, 2024

Self Assembly

Diamond glitter: A play of colors with artificial DNA crystals May 17th, 2024

Liquid crystal templated chiral nanomaterials October 14th, 2022

Nanoclusters self-organize into centimeter-scale hierarchical assemblies April 22nd, 2022

Atom by atom: building precise smaller nanoparticles with templates March 4th, 2022

Nanomedicine

NYU Abu Dhabi researchers develop novel covalent organic frameworks for precise cancer treatment delivery: NYU Abu Dhabi researchers develop novel covalent organic frameworks for precise cancer treatment delivery September 13th, 2024

Unveiling the power of hot carriers in plasmonic nanostructures August 16th, 2024

Nanobody inhibits metastasis of breast tumor cells to lung in mice: “In the present study we describe the development of an inhibitory nanobody directed against an extracellular epitope present in the native V-ATPase c subunit.” August 16th, 2024

The mechanism of a novel circular RNA circZFR that promotes colorectal cancer progression July 5th, 2024

Discoveries

Energy transmission in quantum field theory requires information September 13th, 2024

Breakthrough in proton barrier films using pore-free graphene oxide: Kumamoto University researchers achieve new milestone in advanced coating technologies September 13th, 2024

Quantum researchers cause controlled ‘wobble’ in the nucleus of a single atom September 13th, 2024

New nanomaterial could transform how we visualise fingerprints: Innovative nanomaterials have the potential to revolutionise forensic science, particularly in the detection of latent (non-visible) fingermarks September 13th, 2024

Announcements

Giving batteries a longer life with the Advanced Photon Source: New research uncovers a hydrogen-centered mechanism that triggers degradation in the lithium-ion batteries that power electric vehicles September 13th, 2024

NYU Abu Dhabi researchers develop novel covalent organic frameworks for precise cancer treatment delivery: NYU Abu Dhabi researchers develop novel covalent organic frameworks for precise cancer treatment delivery September 13th, 2024

New discovery aims to improve the design of microelectronic devices September 13th, 2024

New method in the fight against forever chemicals September 13th, 2024

Military

Single atoms show their true color July 5th, 2024

NRL charters Navy’s quantum inertial navigation path to reduce drift April 5th, 2024

What heat can tell us about battery chemistry: using the Peltier effect to study lithium-ion cells March 8th, 2024

The Access to Advanced Health Institute receives up to $12.7 million to develop novel nanoalum adjuvant formulation for better protection against tuberculosis and pandemic influenza March 8th, 2024

Energy

Unveiling the power of hot carriers in plasmonic nanostructures August 16th, 2024

Groundbreaking precision in single-molecule optoelectronics August 16th, 2024

Development of zinc oxide nanopagoda array photoelectrode: photoelectrochemical water-splitting hydrogen production January 12th, 2024

Shedding light on unique conduction mechanisms in a new type of perovskite oxide November 17th, 2023

Nanobiotechnology

NYU Abu Dhabi researchers develop novel covalent organic frameworks for precise cancer treatment delivery: NYU Abu Dhabi researchers develop novel covalent organic frameworks for precise cancer treatment delivery September 13th, 2024

Nanobody inhibits metastasis of breast tumor cells to lung in mice: “In the present study we describe the development of an inhibitory nanobody directed against an extracellular epitope present in the native V-ATPase c subunit.” August 16th, 2024

The mechanism of a novel circular RNA circZFR that promotes colorectal cancer progression July 5th, 2024

A New Blue: Mysterious origin of the ribbontail ray’s electric blue spots revealed July 5th, 2024

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project