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Dynamic nanomachines for DNA nanotechnology inspired by proteins

Posted by Jim Lewis on June 4th, 2015

This is an artist's impression of shape-complementary DNA components that self-assemble into nanoscale machinery. CREDIT C. Hohmann / NIM

Several of our most recent posts on DNA origami and structural DNA nanotechnology have cited research aimed at creating more mechanically dynamic structures (here, here, and here). Another approach to using DNA origami to make nanomachines with moving parts has been published by a German research group inspired by how proteins function by forming and reconfiguring relatively weak bonds. A hat tip to ScienceDaily for reprinting this Technische Universitaet Muenchen news release published on AAAS EurekAlert “Designer’s toolkit for dynamic DNA nanomachines: Arm-waving nanorobot signals new flexibility in DNA origami“:

The latest DNA nanodevices created at the Technische Universitaet Muenchen (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 [abstract] 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.”

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Preserving protein function in DNA-protein nanostructures

Posted by Jim Lewis on June 1st, 2015

(A) Single-stranded M13 DNA (dark blue) and complementary DNA oligonucleotides (golden-rods), two of which have been chemically linked to two different peptides, each containing a GGG site that identifies the N-terminal recognition site of sortase. (B) Annealing places each peptide one third of the way from one end of the M13 DNA. (C) Treatment with sortase and protein CDH23 containing the C-terminal recognition sequence for sortase links protein CDH23 to the GGG-modified oligonucleotide one third from the right of the M13. The other oligo is protected because its N terminus is blocked by the Flag-TEV sequence. (D) Addition of the TEV protease removes the block. (E) Addition of sortase and the PCDH15 protein, also containing the C-terminal recognition sequence for sortase, places that protein on the site at the left. Under conditions in which CDH23 and PCDH15 bind, the loop closes, producing a shorter end-to-end length of the nanoswitch. Credit: Koussa et al. Methods.

We have frequently cited (for example, here, here, and here) the importance of modular molecular composite nanosystems (MMCNs} for the development of atomically precise productive nanosystems and eventually atomically precise manufacturing. One of the recommendations made by the 2007 Productive Nanosystems Technology Roadmap (Executive Summary, p. xi) to support the development of MMCNs is to “Develop systematic methodologies for building MMCNs in which proteins bind specific functional components to specific sites on DNA structural frameworks.” Two months ago, while researching DNA nanoswitches developed by Wesley Wong’s research group to study molecular interactions, I noted on his lab’s publications page a major contribution to achieving this objective through addressing a practical problem that could occur when making DNA-protein nanostructures “Protocol for sortase-mediated construction of DNA-protein hybrids and functional nanostructures” (open access). The abstract of the paper:

Recent methods in DNA nanotechnology are enabling the creation of intricate nanostructures through the use of programmable, bottom-up self-assembly. However, structures consisting only of DNA are limited in their ability to act on other biomolecules. Proteins, on the other hand, perform a variety of functions on biological materials, but directed control of the self-assembly process remains a challenge. While DNA–protein hybrids have the potential to provide the best-of-both-worlds, they can be difficult to create as many of the conventional techniques for linking proteins to DNA render proteins dysfunctional. We present here a sortase-based protocol for covalently coupling proteins to DNA with minimal disturbance to protein function. To accomplish this we have developed a two-step process. First, a small synthetic peptide is bioorthogonally and covalently coupled to a DNA oligo using click chemistry. Next, the DNA–peptide chimera is covalently linked to a protein of interest under protein-compatible conditions using the enzyme sortase. Our protocol allows for the simple coupling and purification of a functional DNA–protein hybrid. We use this technique to form oligos bearing cadherin-23 and protocadherin-15 protein fragments. Upon incorporation into a linear M13 scaffold, these protein–DNA hybrids serve as the gate to a binary nanoswitch. The outlined protocol is reliable and modular, facilitating the construction of libraries of oligos and proteins that can be combined to form functional DNA–protein nanostructures. These structures will enable a new class of functional nanostructures, which could be used for therapeutic and industrial processes.

The introduction to the paper points out that many chemistries conventionally used to link proteins and DNA react with functional groups that are ubiquitous in biology so that the DNA oligo could react to amy of several sites on the protein, increasing the risk of interfering with protein function. This risk is avoided by coupling the DNA oligo to a small, synthetic peptide, so there is no need to optimize coupling protocols for each protein. The protein of interest is then coupled to this DNA-peptide chimera using sortase, a microbial enzyme that recognizes a short amino acid sequence LPX1TGX2 near the C-terminus of one protein and couples it to a GGG sequence at the N-terminus of another protein to produce a fusion of the two proteins. The variant of sortase used was evolved to optimize coupling under conditions favorable for protein stability. Thus all of the chemistry that might be damaging to proteins is front-loaded so that is performed on a small peptide designed to be compatible with those conditions. The peptide can also be designed to facilitate easy purification of the DNA oligo-synthetic peptide-fusion protein. The end result of this process is that it is straight-forward to systematically build a library of proteins linked to DNA oligos, which can then be used to bind any of those proteins to any desired site on a DNA origami structure.

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Single molecule pump concentrates small molecules

Posted by Jim Lewis on May 26th, 2015

Credit: Stoddart research group, Northwestern University

Among the classes of molecular machines that make life possible are the protein pumps that move ions and small molecules across membranes, from one compartment to another. These ions and molecules are driven uphill energetically, from low concentrations to high concentrations, forming systems that are high in energy and can perform work on their environments. Demonstration of this basic principle using a much smaller artificial molecular pump comes this month from the laboratory of Sir Fraser Stoddart, winner of the 2007 Feynman Prize in Nanotechnology in the Experimental category. Hat tips to and ECN for reprinting this Northwestern University news release written by Megan Fellman “Nature inspires first artificial molecular pump“:

Using nature for inspiration, a team of Northwestern University scientists is the first to develop an entirely artificial molecular pump, in which molecules pump other molecules. This tiny machine is no small feat. The pump one day might be used to power other molecular machines, such as artificial muscles.

The new machine mimics the pumping mechanism of life-sustaining proteins that move small molecules around living cells to metabolize and store energy from food. For its food, the artificial pump draws power from chemical reactions, driving molecules step-by-step from a low-energy state to a high-energy state — far away from equilibrium.

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Conference video: Microscopic Reversibility: The Organizing Principle for Molecular Machines

Posted by Jim Lewis on May 13th, 2015

Credit: Dean Astumian

A select set of videos from the 2013 Foresight Technical Conference: Illuminating Atomic Precision, held January 11-13, 2013 in Palo Alto, have been made available on vimeo. Videos have been posted of those presentations for which the speakers have consented. Other presentations contained confidential information and will not be posted.

The second speaker at the Molecular Machines and Non-Equilibrium Processes session, the winner of the 2011 Feynman Prize for Theoretical work, Dean Astumian, presented his prize-winning work “Microscopic Reversibility: The Organizing Principle for Molecular Machines” biography and abstract, – video length 42:12. He addressed how we should think about molecular machines, and in particular, molecular machines inspired by biology, which operate in water at slightly more than room temperature. A molecule called kinesin converts chemical energy from the hydrolysis of ATP (adenosine triphosphate) to walk in one direction on a molecular track called a microtubule. We could try to think of it in terms of a macroscopic deterministic picture, as in mechanics, or we could think of it in probabilistic terms more consistent with chemistry.

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Conference video: Multi-Million Atom Simulations for Single Atom Transistor Structures

Posted by Jim Lewis on May 12th, 2015

Credit:Gerhard Klimeck

A select set of videos from the 2013 Foresight Technical Conference: Illuminating Atomic Precision, held January 11-13, 2013 in Palo Alto, have been made available on vimeo. Videos have been posted of those presentations for which the speakers have consented. Other presentations contained confidential information and will not be posted.

The 8th speaker at the Atomic Scale Devices session was Gerhard Klimeck. His talk was titled “Multi-Million Atom Simulations for Single Atom Transistor Structures” biography and abstracts, video – video length 26:37.

From an electrical engineer’s perspective, Prof. Klimeck began with the observation that over the years the number of transistors on a chip has increased exponentially to more than two billion transistors on a chip, but for the last six to eight year the clock speed has not increased beyond two gigahertz because the power consumption on the chip, about 100 watts per square centimeter, limits the clock speed. Currently the major contribution to this power consumption is “static power”—the power leaking through the transistor whether it is switching or not. The amount of leakage is a fundamental limit of the thermal distribution of charge carriers in the CMOS chip. A solution would be to develop a tunneling transistor that is no longer thermally limited, but instead gives current flow in a narrow energy window. Modeling potential solutions, such as a double gate or a nanowire, to see how current flow can be modulated by the gate of transistor requires an atomistic modeling tool. We and others have shown that nanowire gates can dramatically reduce voltage, so that tunneling transistors may be able to solve the power consumption problem, but perhaps only for a short time. One multi-gate device called a finFET depends on a thin silicon “fin”, so that although the device is nominally a 22-nm device, the active region is only 8 nm wide—64 atoms. In devices currently of interest the number of critical atoms can be as low as 14. This is the reason Klimeck’s group has been building their NEMO (NanoElectronicMOdeling) tool. Further, the number of electrons under the gate in today’s technology is already in the hundreds and is rapidly approaching the tens. So the regime of single electron and quantum dot devices is not so far away. Thus Klimeck’s NEMO tool spans the range from modeling current devices to designing single electron and quantum dot devices.

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Nanoparticles shepherd DNA into cells to regulate immune response

Posted by Jim Lewis on May 6th, 2015

Credit Mirkin research group

One of biotechnology’s most powerful tools is the introduction of nucleic acids of specific sequence into cells to implement a specific pre-determined change. Not surprisingly, nucleic acids incorporated into nanostructures are often much more functional than isolated nucleic acid molecules. It is sometimes not necessary for such nanostructures to be totally atomically precise, as has been demonstrated by Spherical Nucleic Acids (SNAs), dense conjugates of oriented nucleic acids on the surfaces of various nanoparticles, introduced by Chad Mirkin, winner of the 2002 Feynman Prize in Nanotechnology, Experimental. An informative animation available on the Mirkin group web site shows how SNAs are constructed and explains the advantages of SNAs, such as efficient entry into cells via endocytosis, resistance to nucleases, lack of unintended immunogenicity, and much better binding to intracellular nucleic acid targets. A recent success of the Mirkin group with SNAs is described over at “Spherical nucleic acids train immune system to fight disease“:

A research team led by Northwestern University nanomedicine expert Chad A. Mirkin and Sergei Gryaznov of AuraSense Therapeutics has shown that spherical nucleic acids (SNAs) can be used as potent drugs to effectively train the immune system to fight disease, by either boosting or dampening the immune response. The initial treatment triggers a cell-specific immune response all over the body.

By increasing the body’s immune response toward a specific cell type, SNAs could be used to target anything from influenza to different forms of cancer. They also can be used to suppress the immune response, a tactic important in treating autoimmune disorders, such as rheumatoid arthritis and psoriasis, where the body’s immune system mistakenly attacks healthy tissues.

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Nanowires and bacteria harnessed for artificial photosynthesis

Posted by Jim Lewis on May 4th, 2015

This break-through artificial photosynthesis system has four general components: (1) harvesting solar energy, (2) generating reducing equivalents, (3) reducing CO2 to biosynthetic intermediates, and (4) producing value-added chemicals. Credit Berkeley Lab

One of the major areas in which improved precision in our control of matter is likely to deliver major benefits is the area of energy technology, as evidenced by Foresight Institute’s 2014 Workshop on Directed/Programmable Matter for Energy. Gayle Pergamit forwards this news of a major advance in artificial photosynthesis made possible by current-day nanotechnology. A hat tip to Controlled Environments for reprinting this Berkeley Lab news release written by Lynn Yarris “Major Advance in Artificial Photosynthesis Poses Win/Win for the Environment“:

A potentially game-changing breakthrough in artificial photosynthesis has been achieved with the development of a system that can capture carbon dioxide emissions before they are vented into the atmosphere and then, powered by solar energy, convert that carbon dioxide into valuable chemical products, including biodegradable plastics, pharmaceutical drugs and even liquid fuels.

Scientists with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have created a hybrid system of semiconducting nanowires and bacteria that mimics the natural photosynthetic process by which plants use the energy in sunlight to synthesize carbohydrates from carbon dioxide and water. However, this new artificial photosynthetic system synthesizes the combination of carbon dioxide and water into acetate, the most common building block today for biosynthesis.

“We believe our system is a revolutionary leap forward in the field of artificial photosynthesis,” says Peidong Yang, a chemist with Berkeley Lab’s Materials Sciences Division and one of the leaders of this study. “Our system has the potential to fundamentally change the chemical and oil industry in that we can produce chemicals and fuels in a totally renewable way, rather than extracting them from deep below the ground.”

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Science and technology roadmaps for nanotechnology

Posted by Jim Lewis on May 3rd, 2015

From the cover of the European Science and Technology Roadmap for Graphene, Related Two-Dimensional Crystals, and Hybrid Systems.

A decade ago Foresight participated in a two-year effort to produce the first technology roadmap from current, incremental nanotechnology to productive nanosystems capable of general purpose, high-throughput atomically precise manufacturing (APM). The purpose of roadmaps, such as the well-known and extremely successful International Technology Roadmap for Semiconductors, is to define the future technology requirements for complex systems so that present-day research world-wide can be coordinated to develop all the necessary components for the future target system, be it a next generation semiconductor fabrication facility for computer chips, or a nanofactory.

With ITRS the challenge is to develop the next generation of a mature, commercially successful technology. With APM the first generation does not yet exist so the challenge is how to go from a set of disparate enabling technologies, including various molecular sciences and surface physics, to the first functional prototype of a nanofactory. With ITRS the current and earlier technology generations have enabled a flourishing industry that lies at the foundation of much of the world economy and has vast financial resources, providing ample incentive to develop the next generation of the technology. With APM there is no legacy of previous generations, so the incentive to develop the first generation has to come from industries and needs served by different technologies (molecular sciences like chemistry and biotechnology, materials science) that could benefit by extension or replacement of those technologies with APM.

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Nanothreads formed from smallest possible diamonds

Posted by Jim Lewis on May 2nd, 2015

Diamond nanothreads promise extraordinary properties, including strength and stiffness greater than that of today's strongest nanotubes and polymers. The core of the nanothreads is a long, thin strand of carbon atoms arranged just like the fundamental unit of a diamond structure -- zig-zag cyclohexane rings of six carbon atoms bound together, in which each carbon is surrounded by others in the strong triangular-pyramid shape of a tetrahedron. The threads, made for the first time by a team led by John V. Badding of Penn State University, have a structure that has never been seen before. Credit: Enshi Xu, Vincent Crespi lab, Penn State University

A few months ago we cited a report of a new form of carbon—penta-graphene—that had been computationally simulated but not yet synthesized. Foresight Co-Founder Christine Peterson forwarded a link to this publication a couple months ago that reported the mechanical properties of yet another form of carbon—diamond nanothreads. This Nano Letters abstract reports that, based on molecular dynamics simulations, diamond nanothreads have a stiffness comparable to carbon nanotubes and a tenacity (specific strength) exceeding carbon nanotubes and graphene.

A Penn State news release reported the first production of diamond nanothreads last September “Smallest Possible Diamonds Form Ultra-thin Nanothreads“:

21 September 2014 — For the first time, scientists have discovered how to produce ultra-thin “diamond nanothreads” that promise extraordinary properties, including strength and stiffness greater than that of today’s strongest nanotubes and polymers. A paper describing this discovery by a research team led by John V. Badding, a professor of chemistry at Penn State University, will be published in the 21 September 2014 issue of the journal Nature Materials [abstract].

“From a fundamental-science point of view, our discovery is intriguing because the threads we formed have a structure that has never been seen before,” Badding said. The core of the nanothreads that Badding’s team made is a long, thin strand of carbon atoms arranged just like the fundamental unit of a diamond’s structure — zig-zag “cyclohexane” rings of six carbon atoms bound together, in which each carbon is surrounded by others in the strong triangular-pyramid shape of a tetrahedron. “It is as if an incredible jeweler has strung together the smallest possible diamonds into a long miniature necklace,” Badding said. “Because this thread is diamond at heart, we expect that it will prove to be extraordinarily stiff, extraordinarily strong, and extraordinarily useful.”

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UK SuperSTEM facility advances imaging and analysis of materials

Posted by Jim Lewis on April 30th, 2015

SuperSTEM2, a Nion UltraSTEM 100 microscope. Credit: EPSRC

In his classic 1959 talk “There’s Plenty of Room at the Bottom: An Invitation to Enter a New Field of Physics” Richard P. Feynman challenged his fellow physicists to make the electron microscope 100 times better:

… It is very easy to answer many of these fundamental biological questions; you just look at the thing! You will see the order of bases in the chain; you will see the structure of the microsome. Unfortunately, the present microscope sees at a scale which is just a bit too crude. Make the microscope one hundred times more powerful, and many problems of biology would be made very much easier. …

But if the physicists wanted to, they could also dig under the chemists in the problem of chemical analysis. It would be very easy to make an analysis of any complicated chemical substance; all one would have to do would be to look at it and see where the atoms are. The only trouble is that the electron microscope is one hundred times too poor. …

I put this out as a challenge: Is there no way to make the electron microscope more powerful? …

Foresight Co-Founder Christine Peterson points to this announcement that shows Feynman’s challenge has been answered. A hap tip to for reprinting this EPSRC press release “EPSRC unveils world-leading SuperSTEM microscope that sees single atoms“:

A new super powerful electron microscope that can pinpoint the position of single atoms, and will help scientists push boundaries even further, in fields such as advanced materials, healthcare and power generation, will be unveiled today, Thursday 19 February, by the Engineering and Physical Sciences Research Council (EPSRC).

The £3.7 million Nion Hermes Scanning Transmission Electron Microscope, one of only three in the world, will be sited at the EPSRC SuperSTEM facility at the Daresbury laboratory complex near Warrington, which is part of the Science and Technology Facilities Council (STFC).

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Gold nanotubes engineered for diagnosis and therapy

Posted by Jim Lewis on April 30th, 2015

Pulsed near infrared light (shown in red) is shone onto a tumour (shown in white) that is encased in blood vessels. The tumour is imaged by multispectral optoacoustic tomography via the ultrasound emission (shown in blue) from the gold nanotubes. Image credit: Jing Claussen (iThera Medical, Germany)

Across a range of applications, the move from limited control of nanostructure toward the goal of eventual atomic precision is providing increased functional capabilities. Foresight President Paul Melnyk sends this example from Medgadget (written by Joshua Chen) of added benefits from controlling the length of gold nanotubes “Advancements In Gold Nanotechnology for Fighting Cancer“:

A study published in the scientific journal Advanced Functional Materials [abstract] describes for the first time the treatment of a human cancer in a mouse model using gold nanotubes. The group is able to control the length and tunable absorption of these gold nanoparticles in the near-infrared (NIR) region using a length-controlled synthesis method. They then apply a coating of poly(sodium 4-styrenesulfonate) (PSS) to allow the nanoparticles to maintain colloidal properties while maintaining low cytotoxicity. …

Further details are contained in a University of Leeds news release “Gold nanotubes launch a three-pronged attack on cancer cells“:

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Foresight Institute Awards Feynman Prizes in Nanotechnology to Amanda S. Barnard, Joseph W. Lyding

Posted by Jim Lewis on April 23rd, 2015

Amanda S. Barnard (Theory) and Joseph W. Lyding (Experimental)

Feynman Prize winners for 2014 Amanda S. Barnard (Theory) and Joseph W. Lyding (Experimental).

Palo Alto, CA – April 23, 2015 – Foresight Institute, a leading think tank and public interest organization focused on molecular nanotechnology, announced the winners for the 2014 Foresight Institute Feynman Prizes. These prestigious prizes, named in honor of pioneer physicist Richard Feynman, are given in two categories, one for experiment and the other for theory in nanotechnology. Established in 1993, these prizes honor researchers whose recent work has most advanced the achievement of Feynman’s goal for nanotechnology: the construction of atomically-precise products through the use of productive nanosystems.

“The Foresight Institute Feynman Prizes in nanotechnology are among the most prestigious awards in science,” said Paul Melnyk, President of Foresight Institute. “Molecular nanotechnology is defined as the construction of atomically-precise products through the use of molecular machine systems.”

“Foresight Institute established these prizes to encourage research in the development of molecular nanotechnology. The Foresight Institute Feynman Prizes are awarded to those making significant advances toward that end,” said Christine Peterson, Co-Founder and Vice President of Foresight Institute. “Productive nanosystems will result in the ultimate manufacturing technology. This capability will help us tackle fundamental problems that face humanity and lead to solutions that are good for people and good for the planet.”

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Solid-phase synthesis of custom-made DNA nanotubes

Posted by Jim Lewis on April 9th, 2015

Nanotube scaffold. Credit: McGill University

A year ago we cited the development of “Bigger, stiffer, roomier molecular cages from structural DNA nanotechnology“. Another research group has just published a different method to achieve a similar goal: building scaffolds to organize functional components. A hat tip to for describing this new method for fabricating DNA nanotubes. The McGill University news release “Building tailor-made DNA nanotubes step by step“:

Researchers at McGill University have developed a new, low-cost method to build DNA nanotubes block by block – a breakthrough that could help pave the way for scaffolds made from DNA strands to be used in applications such as optical and electronic devices or smart drug-delivery systems.

Many researchers, including the McGill team, have previously constructed nanotubes using a method that relies on spontaneous assembly of DNA in solution. The new technique, reported today in Nature Chemistry [abstract], promises to yield fewer structural flaws than the spontaneous-assembly method. The building-block approach also makes it possible to better control the size and patterns of the DNA structures, the scientists report.

“Just like a Tetris game, where we manipulate the game pieces with the aim of creating a horizontal line of several blocks, we can now build long nanotubes block by block,” said Amani Hariri, a PhD student in McGill’s Department of Chemistry and lead author of the study. “By using a fluorescence microscope we can further visualize the formation of the tubes at each stage of assembly, as each block is tagged with a fluorescent compound that serves as a beacon. We can then count the number of blocks incorporated in each tube as it is constructed.”

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Flexible supercapacitor from stacked nanomaterial

Posted by Jim Lewis on April 8th, 2015

A schematic shows the process developed by Rice University scientists to make vertical microsupercapacitors with laser-induced graphene. The flexible devices show potential for use in wearable and next-generation electronics. Courtesy of the Tour Group

The exceptional properties of nanomaterials can make them useful in ways that are not immediately obvious. A hat tip to for reporting a new supercapacitor based on a novel material derived from graphene. This is yet another advance from the laboratory of James Tour, winner of the 2008 Feynman Prize in Nanotechnology in the Experimental category. From a Rice University news release written by Mike Williams “Laser-induced graphene ‘super’ for electronics“:

Rice University researchers test flexible, three-dimensional supercapacitors

Rice University scientists advanced their recent development of laser-induced graphene (LIG) by producing and testing stacked, three-dimensional supercapacitors, energy-storage devices that are important for portable, flexible electronics.

The Rice lab of chemist James Tour discovered last year that firing a laser at an inexpensive polymer burned off other elements and left a film of porous graphene, the much-studied atom-thick lattice of carbon. The researchers viewed the porous, conductive material as a perfect electrode for supercapacitors or electronic circuits.

To prove it, members of the Tour group have since extended their work to make vertically aligned supercapacitors with laser-induced graphene on both sides of a polymer sheet. The sections are then stacked with solid electrolytes in between for a multilayer sandwich with multiple microsupercapacitors.

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DNA nanoswitches open window on molecular interactions

Posted by Jim Lewis on April 5th, 2015

Gel electrophoresis, a common laboratory process, sorts DNA or other small proteins by size and shape using electrical currents to move molecules through small pores in gel. The process can be combined with novel DNA nanoswitches, developed by Wyss Associate Faculty member Wesley Wong, to allow for the simple and inexpensive investigation of life's most powerful molecular interactions. Credit: Wyss Institute at Harvard University

Part of the problem in building complex molecular machine systems—whether the evolved systems that are the foundation of biology, or the artificial systems being designed to implement various nanotechnology applications eventually leading to high-throughput atomically precise manufacturing (APM)—is the fabrication and organization of the needed nanostructures. The other part is understanding how these molecular components interact so that these interactions can be orchestrated to accomplish the desired functions. Conventional methods for studying molecular interactions are difficult and expensive, but now a simple form of DNA nanotechnology provides a method to make such studies much more accessible, as described in this press release from the Wyss Institutue “DNA nanoswitches reveal how life’s molecules connect“:

An accessible new way to study molecular interactions could lower cost and time associated with discovering new drugs

A complex interplay of molecular components governs almost all aspects of biological sciences — healthy organism development, disease progression, and drug efficacy are all dependent on the way life’s molecules interact in the body. Understanding these bio–molecular interactions is critical for the discovery of new, more effective therapeutics and diagnostics to treat cancer and other diseases, but currently requires scientists to have access to expensive and elaborate laboratory equipment.

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New scaffold for nanotechnology engineered from amyloid-like proteins

Posted by Jim Lewis on April 4th, 2015

Making spruce budworm antifreeze protein into amyloid fibrils. The cap structure (red) was removed and other structures adjusted so that molecules could link up as fibrils (bottom). Credit: UC Davis

Among the specific recommendations of the 2007 Productive Nanosystems Technology Roadmap is the development of modular molecular composite nanosystems (MMCNs) in which “million-atom-scale DNA frameworks with dense arrays of distinct, addressable, [atomically precise] binding sites” provide scaffolds for organizing various nanoscale functional components (page x of Executive Summary of Productive Nanosystems: A Technology Roadmap PDF). Despite the obvious advantages of large DNA scaffolds, other possibilities are conceivable. Would protein scaffolds engineered for tissue engineering or other applications be suitable? A hat tip to for reporting this news release from UC Davis “Engineering self-assembling amyloid fibers“:

Nature has many examples of self-assembly, and bioengineers are interested in copying or manipulating these systems to create useful new materials or devices. Amyloid proteins, for example, can self-assemble into the tangled plaques associated with Alzheimer’s disease — but similar proteins can also form very useful materials, such as spider silk, or biofilms around living cells. Researchers at UC Davis and Rice University have now come up with methods to manipulate natural proteins so that they self-assemble into amyloid fibrils. The paper is published online by the journal ACS Nano.

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Cotranscriptional folding of single RNA strand added to nanotechnology toolkit

Posted by Jim Lewis on March 31st, 2015

Artist's impression of RNA nanostructures that can fold up while they are being synthesized by polymerase enzymes that read DNA templates. Once formed, the RNAs assemble into hexagonal lattices on the mica surface below. Credit: Cody Geary.

We have drawn attention here to RNA nanotechnology because RNA can function as a genetic material, as can DNA, so it has a molecular recognition code similar (but not identical) to that of DNA, but it can also assume a wider range of secondary structures than can DNA, and thus can also function catalytically, as do proteins. Since the replication and transmission of genetic information and the catalysis of chemical reactions are the two most basic functions of the molecular machinery of life, it is of considerable interest to explore what role RNA nanotechnology could play in developing the artificial molecular machine systems that will lead both to near term advances in various areas of nanotechnology and to the ultimate development of high-throughput atomically precise manufacturing (APM). Structural DNA nanotechnology predates RNA nanotechnology by a decade or more, and one of key developments in building more complex nanostructures and devices from DNA has been DNA origami. So, what might we expect from last summer’s introduction of RNA origami? A hat tip to ScienceDaily for reprinting this news release from Aarhus University, and for adding an extremely useful “RNA fact sheet” at the bottom of the article that summarizes the key roles of RNA and the differences in structure and function between RNA and DNA. “Scientists Fold RNA Origami From a Single Strand“:

RNA origami is a new method for organizing molecules on the nanoscale. Using just a single strand of RNA, many complicated shapes can be fabricated by this technique. Unlike existing methods for folding DNA molecules, RNA origamis are produced by enzymes and they simultaneously fold into pre-designed shapes. These features may allow designer RNA structures to be grown within living cells and used to organize cellular enzymes into biochemical factories. The method, which was developed by researchers from Aarhus University (Denmark) and California Institute of Technology (Pasadena, USA), is reported in the latest issue of Science [abstract].

Origami, the Japanese art of paper folding, derives its elegance and beauty from the manipulation of a single piece of paper to make a complex shape. The RNA origami method described in the new study likewise involves the folding of a single strand of RNA, but instead of the experimenters doing the folding, the molecules fold up on their own.

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Automated synthesis expands nanotechnology building block repertoire

Posted by Jim Lewis on March 24th, 2015

A machine in University of Illinois chemistry professor Martin Burke's lab assembles complex small molecules out of simple chemical building blocks, like a 3-D printer on the molecular level. Credit: University of Illinois. Photo by L. Brian Stauffer

High-throughput atomically precise manufacturing (APM) has been described as a manufacturing technology that could be developed over the next few decades that could radically change civilization (Radical Abundance). APM has been alternatively referred to as “molecular nanotechnology”, “molecular manufacturing” and “productive nanosystems”.

For a very limited class of objects, chemists have been doing APM for two centuries by synthesizing small to mid-size molecules to atomic precision (plus large molecules with repeating subunits, like polymers and dendrimers). In the case of molecules without repeating subunits, the limits of synthetic chemistry are reached when molecules become large enough that chemists cannot devise methods to add the next group of atoms at one specific site on the growing molecule instead of at other chemically similar sites. In proposals to develop APM, this problem will be solved by guided molecular trajectories and positionally-controlled mechanosynthesis: reactive molecular fragments will be guided by molecular machine systems to a specific position and geometric orientation with respect to the growing atomically precise work piece so that the application of mechanical force will cause the desired bond to form.

APM has also been likened to an atomic scale version of 3D-printing (also called additive manufacturing) in which a small volume element (but a couple orders of magnitude larger than molecular scale) can be added at any arbitrary position to a growing object (see, for example, Radical Abundance pp 76-77). Thus APM and 3D-printing are both manufacturing systems in which arbitrarily complex 3D objects can be manufactured from the bottom-up through the positionally controlled placement of very small elements.

In recent weeks, the blogosphere has greeted a radical advance in synthetic organic chemistry with titles like “3-D Printer for Small Molecules Opens Access to Customized Chemistry” (Phys Org), “Scientists Unveil 3D Printer for Small Molecules” (STGIST), and “This Chemistry 3D Printer Can Synthesize Molecules from Scratch”. To what extent does this huge advance in synthetic chemistry technology amount to bringing the positional control of 3D-printing to the molecular scale? How close does it get us to APM? From the University of Illinois news bureau “Molecule-making machine simplifies complex chemistry”:

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Targeted nanoparticles deliver molecules to resolve atherosclerotic inflammation

Posted by Jim Lewis on March 9th, 2015

Schematic of a targeted nanoparticle with a hydrophilic polymer shell containing targeting ligands and a hydrophobic polymer core containing therapeutic cargo. Credit: Harvard Medical School and Science Translational Medicine.

Our most recent posts (here and here) focused on increasing acceptance of the idea that the ultimate future of nanotechnology rests with high throughput atomically precise manufacturing. This one exemplifies the use of atomically precise elements from biotechnology and chemistry incorporated into non-atomically precise but increasingly sophisticated nanostructures to advance one application area—medicine. In this case the area of medical interest is the number one cause of death in the industrial world: cardiovascular disease. Foresight President Paul Melnyk forwards this link “Nanotechnology ‘could signal the future of medicine’, scientists claim“:

Microscopic drones which can seek out and repair sections of artery damage could signal the future of treatments for heart disease and strokes, scientists claim.

Successful tests of the nanodrones have been carried out in mice – and researchers hope to conduct the first human trials soon.

The tiny particles are 1,000 times smaller than the tip of a human hair, and are designed to latch on to atherosclerotic plaques – hard deposits made from accumulated fat, cholesterol and calcium that build up on the walls of arteries and are prone to rupture, producing dangerous clots.

Once they have attached, they release a drug derived from a natural protein which can repair damage in the body.

In the mice, scientists found that just five weeks of treatment resulted in significant repairs to artery damage while the plaques were shrunk and stabilised, making it less likely for fragments to break off and cause clots.…

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Atomically precise manufacturing as the future of nanotechnology

Posted by Jim Lewis on March 8th, 2015

Screenshot of DNA nanorobot designed using cadnano. Credit: Nature Nanotechnology.

Continuing the theme of our previous post, is the idea of atomically precise manufacturing as the future of nanotechnology accruing credibility in the blogosphere? Over at Gizmodo Jamie Condliffe asks “What Will the Future of Molecular Manufacturing Really Be Like?“:

Molecular machines are nano-scale assemblers that construct themselves and their surroundings into ever more complex structures. Sometimes dubbed “nanotech” in the media, these devices are promising — but also widely misunderstood. Here’s what separates the science fact from science fiction.

The concepts that underpin this form of nanotechnology have certainly had long enough to percolate through modern science. Richard Feynman first speculated about the idea of “synthesis via direct manipulation of atoms” during a talk called There’s Plenty of Room at the Bottom. Looking back, that sparked much of the subsequent thinking about treating atoms and molecules more and more like simple building blocks.

Perhaps most famously, K. Eric Drexler considered the idea of taking the bottom-up manufacturing approach to its atomic extreme in his 1986 book Engines of Creation: The Coming Era of Nanotechnology. There, he posited the idea of a nan-oscale “assembler” that could scuttle around, building copies of itself or other molecular sized objects with atomic control; one which might in turn be able to create larger and more complex structures. A kind of microscopic production line, building products from the most basic ingredients of all. Coming when it did, in the mid-eighties, it felt very much like science fiction. …

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