Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

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

NUS researchers achieve major breakthrough in flexible electronics: New classes of printable electrically conducting polymer materials make better electrodes for plastic electronics and advanced semiconductor devices January 14th, 2017

Manchester scientists tie the tightest knot ever achieved January 13th, 2017

Nanoscale Modifications can be used to Engineer Electrical Contacts for Nanodevices January 13th, 2017

Chemistry on the edge: Experiments at Berkeley Lab confirm that structural defects at the periphery are key in catalyst function January 13th, 2017

Govt.-Legislation/Regulation/Funding/Policy

Chemistry on the edge: Experiments at Berkeley Lab confirm that structural defects at the periphery are key in catalyst function January 13th, 2017

Recreating conditions inside stars with compact lasers: Scientists offer a new path to creating the extreme conditions found in stars, using ultra-short laser pulses irradiating nanowires January 12th, 2017

Deciphering the beetle exoskeleton with nanomechanics: Understanding exoskeletons could lead to new, improved artificial materials January 12th, 2017

New laser based on unusual physics phenomenon could improve telecommunications, computing January 12th, 2017

Chip Technology

NUS researchers achieve major breakthrough in flexible electronics: New classes of printable electrically conducting polymer materials make better electrodes for plastic electronics and advanced semiconductor devices January 14th, 2017

Nanoscale Modifications can be used to Engineer Electrical Contacts for Nanodevices January 13th, 2017

New laser based on unusual physics phenomenon could improve telecommunications, computing January 12th, 2017

NIST physicists 'squeeze' light to cool microscopic drum below quantum limit January 12th, 2017

Self Assembly

Manchester scientists tie the tightest knot ever achieved January 13th, 2017

Captured on video: DNA nanotubes build a bridge between 2 molecular posts: Research may lead to new lines of direct communication with cells January 9th, 2017

Researchers fabricate high performance Cu(OH)2 supercapacitor electrodes December 29th, 2016

Nanoscale 'conversations' create complex, multi-layered structures: New technique leverages controlled interactions across surfaces to create self-assembled materials with unprecedented complexity December 22nd, 2016

Nanomedicine

New active filaments mimic biology to transport nano-cargo: A new design for a fully biocompatible motility engine transports colloidal particles faster than diffusion with active filaments January 11th, 2017

Keystone Nano Announces FDA Approval Of Investigational New Drug Application For Ceramide NanoLiposome For The Improved Treatment Of Cancer January 10th, 2017

Captured on video: DNA nanotubes build a bridge between 2 molecular posts: Research may lead to new lines of direct communication with cells January 9th, 2017

Arrowhead Provides Response to New Minority Shareholder Announcement January 7th, 2017

Discoveries

NUS researchers achieve major breakthrough in flexible electronics: New classes of printable electrically conducting polymer materials make better electrodes for plastic electronics and advanced semiconductor devices January 14th, 2017

Manchester scientists tie the tightest knot ever achieved January 13th, 2017

Nanoscale Modifications can be used to Engineer Electrical Contacts for Nanodevices January 13th, 2017

Chemistry on the edge: Experiments at Berkeley Lab confirm that structural defects at the periphery are key in catalyst function January 13th, 2017

Announcements

NUS researchers achieve major breakthrough in flexible electronics: New classes of printable electrically conducting polymer materials make better electrodes for plastic electronics and advanced semiconductor devices January 14th, 2017

Manchester scientists tie the tightest knot ever achieved January 13th, 2017

Nanoscale Modifications can be used to Engineer Electrical Contacts for Nanodevices January 13th, 2017

Chemistry on the edge: Experiments at Berkeley Lab confirm that structural defects at the periphery are key in catalyst function January 13th, 2017

Military

Manchester scientists tie the tightest knot ever achieved January 13th, 2017

Recreating conditions inside stars with compact lasers: Scientists offer a new path to creating the extreme conditions found in stars, using ultra-short laser pulses irradiating nanowires January 12th, 2017

Deciphering the beetle exoskeleton with nanomechanics: Understanding exoskeletons could lead to new, improved artificial materials January 12th, 2017

New laser based on unusual physics phenomenon could improve telecommunications, computing January 12th, 2017

Energy

Stability challenge in perovskite solar cell technology: New research reveals intrinsic instability issues of iodine-containing perovskite solar cells December 26th, 2016

Nanoscale 'conversations' create complex, multi-layered structures: New technique leverages controlled interactions across surfaces to create self-assembled materials with unprecedented complexity December 22nd, 2016

Safe and inexpensive hydrogen production as a future energy source: Osaka University researchers develop efficient 'green' hydrogen production system that operates at room temperature in air December 21st, 2016

Going green with nanotechnology December 21st, 2016

Nanobiotechnology

Nanoscale Modifications can be used to Engineer Electrical Contacts for Nanodevices January 13th, 2017

New active filaments mimic biology to transport nano-cargo: A new design for a fully biocompatible motility engine transports colloidal particles faster than diffusion with active filaments January 11th, 2017

Keystone Nano Announces FDA Approval Of Investigational New Drug Application For Ceramide NanoLiposome For The Improved Treatment Of Cancer January 10th, 2017

Captured on video: DNA nanotubes build a bridge between 2 molecular posts: Research may lead to new lines of direct communication with cells January 9th, 2017

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




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project