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DOE office focusing on atomically precise manufacturing

David Forrest ScD, PE, FASM
Technology Manager, Advanced Manufacturing Office,
U.S. Department of Energy

Longtime Foresight member David Forrest has been involved with nanotechnology development since his student days at MIT with Foresight co-founders Eric Drexler and Christine Peterson, and since October 2012 he has been Technology Manager, Advanced Manufacturing Office, U.S. Department of Energy. At Foresight Institute’s Breakthrough Technologies for Energy workshop this past spring, Dr. Forrest spoke about “Progress in Atomically Precise Manufacturing at the Advanced Manufacturing Office”. The strategic goals of this effort include developing a suite of manufacturing technologies capable of building a broad range of macroscopic atomically precise products, and transitioning these to commercial practice to transform the U.S. manufacturing base to APM-centric production. The motivation from the standpoint of DOE is to reduce energy use. Current efforts began with a DOE workshop held August 5-6, 2015 in Berkeley, CA “Workshop on Integrated Nanosystems for Atomically Precise Manufacturing“. The six plenary presentations that can be downloaded from the workshop web page comprise arguably the best overview of progress toward APM since Foresight Institute and Battelle unveiled a Technology Roadmap for Productive Nanosystems in 2007. When complete, the workshop report is expected to be available from this page.

To inform the public of the importance of APM, a recent “Nano Nuggets” You Tube video features Dr. Forrest explaining how nanotechnology—specifically atomically precise manufacturing—will impact manufacturing. For example, making membranes with every atom positioned to make molecularly perfect pores to filter clean water from salt water using far less energy.

To focus on the importance of APM for advanced materials for industry, Dr. Forrest visited Austria this past November “AMO’s David Forrest Attends Prestigious George C. Marshall Visit to Austria Program“.

Each year since 2007, the Austrian government has brought industry and technology experts from the United States together through the George C. Marshall Visit to Austria Program. The program is designed to connect U.S. change makers together and to highlight Austrian innovations and build a collaborative relationship between the two countries.

This year, Dr. David Forrest, Technology Manager in the Advanced Manufacturing Office (AMO), received an invitation to join this prestigious delegation focused on advanced materials. Dr. Forrest has more than 30 years of award-winning work across industry, academia, and government. At AMO, his work centers around atomically precise manufacturing, high performance materials, and advanced material processes. Other delegates came from American universities and AMO partners such as Lawrence Berkeley National Laboratory and the National Science Foundation’s Advanced Manufacturing Program.

This November, Dr. Forrest joined eight advanced materials experts from the U.S. in Austria for dialogue with top Austrian universities and companies doing work in advanced materials and processes. The first day of the event, Dr. Forrest joined a panel discussion on “The Role of Advanced Materials in the Industry” which brought together other Marshall delegates along with experts from Austrian universities. …

The profile and scope of the activities of DOE’s Advanced Manufacturing Office seem to be increasing. See tomorrow’s post for news of a new funding opportunity from the Office of Energy Efficiency and Renewable Energy (EERE), on behalf of the Advanced Manufacturing Office.
—James Lewis, PhD

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New Funding Opportunity from U.S. DOE

U.S. Department of Energy Mission Innovation – a joint effort by more than 20 nations to double clean energy R&D by 2020.

David Forrest, Technology Manager, Advanced Manufacturing Office, U.S. Department of Energy, writes with news of a new funding opportunity at DOE:

Dear Friends and Colleagues who have shown some interest in Atomically Precise Manufacturing (APM),

I am pleased to forward this funding opportunity announcement (FOA) to you from the Advanced Manufacturing Office. The FOA includes a range of topics in advanced materials and processes, and explicitly includes a subtopic on Atomically Precise Manufacturing.

Note: scroll down to the line “DE-FOA-0001465 – Advanced Manufacturing Projects for Emerging Research Exploration (Last Updated: 12/21/2016 05:28 PM ET)” Download the PDF and scroll down to page 11/91 – “Subtopic 1.5 – Atomically Precise Manufacturing”

As some of you know, we have been soliciting SBIR projects in this space for several years now but this is the first AMO R&D Projects FOA in this space. And the application space has been expanded from the SBIR offerings—responsive concept papers and proposals will include atomically precise membranes and catalysts, sensors, molecular electronic computer circuits, and also tools and systems to perform APM through positional assembly (whether tip-based, or molecular machine-based–aka molecular additive manufacturing). Announcement is [here].

So there is no confusion, we define APM in the same fashion as the definition from our workshop on this subject, Integrated Nanosystems for Atomically Precise Manufacturing, and, curiously, as in Wikipedia.

Subtopic 1.5 – Atomically Precise Manufacturing

Atomically precise manufacturing is the production of materials, structures, devices, and finished goods in a manner such that every atom is at its specified location relative to the other atoms, and in which there are no defects, missing atoms, extra atoms, or incorrect (impurity) atoms. In current practice, atomically precise molecular sheets are possible using macromolecular chemistry with densely-packed designs for near zero defects, and full cross-linking for near theoretical strength and chemical stability. Spiroligomers, Metal Organic Frameworks, engineered proteins, enzymes, ribozymes, peptoids, and engineered DNA and RNA are examples of atomically precise building blocks that can be crafted for macromolecular assemblies, or which can be designed as atomically precise receptor sites to catalyze chemical reactions. In future practice, more complex atomically precise structures and devices could be fabricated using positional assembly with advanced scanning probe systems, or with integrated nanosystems for molecular additive manufacturing. Advances in these current or future practice techniques will be considered for funding for high energy impact applications such as (but not limited to) atomically precise membranes, atomically precise catalysts, molecular electronic computer circuits, and high sensitivity molecular sensors.

There will be a webinar on January 5th to walk those interested through the basics of the FOA. Please send any inquiries to the email address shown on the FOA website rather than directly to me.

The Informational Webinar mentioned in the FOA will be held on January 5, 2017 at 1:00 PM ET Eastern Standard Time. Please click or copy and paste this link from the FOA into your browser for registration:
—James Lewis, PhD

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Nobel Prize in Chemistry recognizes molecular machines

Sir Fraser receiving the 2007 Foresight Feynman Prize for Experiment

Sir J. Fraser Stoddart, joint winner of the 2016 Nobel Prize in Chemistry, accepting the 2007 Foresight Institute Feynman Prize for Experiment.

The 2016 Nobel Prize in Chemistry was awarded to three scientists who “developed the world’s smallest machines”. From the Royal Swedish Academy of Sciences “Press Release: The Nobel Prize in Chemistry 2016“:

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2016 to
Jean-Pierre Sauvage, University of Strasbourg, France
Sir J. Fraser Stoddart, Northwestern University, Evanston, IL, USA, and
Bernard L. Feringa, University of Groningen, the Netherlands
“for the design and synthesis of molecular machines” …

A tiny lift, artificial muscles and minuscule motors. The Nobel Prize in Chemistry 2016 is awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for their design and production of molecular machines. They have developed molecules with controllable movements, which can perform a task when energy is added.

The development of computing demonstrates how the miniaturisation of technology can lead to a revolution. The 2016 Nobel Laureates in Chemistry have miniaturised machines and taken chemistry to a new dimension.

The first step towards a molecular machine was taken by Jean-Pierre Sauvage in 1983, when he succeeded in linking two ring-shaped molecules together to form a chain, called a catenane. Normally, molecules are joined by strong covalent bonds in which the atoms share electrons, but in the chain they were instead linked by a freer mechanical bond. For a machine to be able to perform a task it must consist of parts that can move relative to each other. The two interlocked rings fulfilled exactly this requirement.

The second step was taken by Fraser Stoddart in 1991, when he developed a rotaxane. He threaded a molecular ring onto a thin molecular axle and demonstrated that the ring was able to move along the axle. Among his developments based on rotaxanes are a molecular lift, a molecular muscle and a molecule-based computer chip.

Bernard Feringa was the first person to develop a molecular motor; in 1999 he got a molecular rotor blade to spin continually in the same direction. Using molecular motors, he has rotated a glass cylinder that is 10,000 times bigger than the motor and also designed a nanocar.

2016′s Nobel Laureates in Chemistry have taken molecular systems out of equilibrium’s stalemate and into energy-filled states in which their movements can be controlled. In terms of development, the molecular motor is at the same stage as the electric motor was in the 1830s, when scientists displayed various spinning cranks and wheels, unaware that they would lead to washing machines, fans and food processors. Molecular machines will most likely be used in the development of things such as new materials, sensors and energy storage systems.

The award of this chemistry Nobel demonstrates that the scientific establishment is moving toward the vision of constructing atomically-precise products through the use of systems of molecular machines. This vision was first elucidated by Nobel laureate physicist Richard Feynman, who proposed in 1959 that “The problems of chemistry and biology can be greatly helped if our ability to see what we are doing, and to do things on an atomic level, is ultimately developed — a development which I think cannot be avoided.” The Foresight Institute was founded in 1986 on a vision of the emerging field of nanotechnology in which current capabilities in several areas of science and technology lead eventually to fabrication of complex products with atom-by-atom control of the manufacturing process. This vision was inspired by analogy with the biological molecular machines that form the basis of life, with the added insight that biology points “to the development of general capabilities for molecular manipulation”, initially termed molecular engineering.

Although Foresight’s initial focus on molecular engineering paths to molecular nanotechnology was on protein engineering, it was soon (1987) realized that relatively simple organic molecules could perform functions like those of natural proteins. A few years after he began working on rotaxanes—work recognized by the Nobel this year—J. Fraser Stoddart, then at the University of Birmingham, spoke in 1995 at the Fourth Foresight Conference on Molecular Nanotechnology on “The Art and Science of Self-Assembling Molecular Machines“. Eight years later Stoddart, then at the California NanoSystems Institute/Department of Chemistry and Biochemistry, University of California, Los Angeles, was a keynote speaker at the 11th Foresight Conference on Molecular Nanotechnology, speaking on “Meccano on the NanoScale: A Blueprint for Making Some of the World’s Tiniest Machines“.

In 2007, Sir Fraser, by then at Northwestern University, was recognized by the award of Foresight’s 2007 Feynman Prize in Nanotechnology in the Experiment category for pioneering “the synthesis and assembly of unique active molecular machines for manufacturing into practical nanoscale devices. His many accomplishments in synthetic chemistry have produced functional molecular machines, in particular a ‘molecular muscle’ for the purposes of amplifying and harnessing molecular mechanical motions, that may ultimately lead to the construction of atomically-precise products through the use of molecular machine systems.” In accepting the award, Sir Fraser commented that the Feynman awards that year represented a unique, scientific “father and son” celebration since the winner in the Theory category was David A. Leigh, then of the University of Edinburgh, for “the design and synthesis of artificial molecular motors and machines from first principles” … “focusing on the construction of molecular machine systems that function in the realm of Brownian motion”. Prof. Leigh had obtained his PhD in 1987 under Prof. Stoddart’s supervision at the University of Sheffield.

At Foresight Institute’s 25th Anniversary Reunion Conference in 2011 Sir Fraser spoke on “Integrating Molecular Switches and Machines with the Everyday World”. He co-chaired the 2013 Foresight Conference “Illuminating Atomic Precision“, chaired the session on “Molecular Machines and Non-Equilibrium Processes”, and lectured on “Autonomous Artificial Molecular Transport”. His most recent work that was featured in this blog includes addressable molecular machines arranged in a porous crystal (September, 2015) and an artificial molecular pump (May 2015). The graduate student who was first author of the molecular pump paper (Chuyang Cheng, now a postdoctoral researcher in Stoddart’s group) won Foresight’s 2015 Distinguished Student Award, the second of Prof. Stoddart’s graduate students to win this award. Finally, we noted in December of 2011 that Prof. Stoddart co-authored a review of molecular machines that addressed whether artificial molecular machines could deliver the performance that visionaries expect. His senior co-authors of that review subsequently themselves became Foresight Feynman prize winners: R. Dean Astumian (2011, Theory category), and Bartosz A. Grzybowski (2016, Theory category).

The discovery by Jean-Pierre Sauvage in 1983 of the mechanical bond, which made possible the avalanche of work on molecular machines, occurred several years before Foresight came into existence; however, in June of 2011 we pointed to a major book co-edited by Prof. Sauvage on supramolecular chemistry and molecular machines, published that year, that collected papers and discussions from the 21st Solvay Conference on Chemistry (held in 2007). The third Nobel laureate, Prof. Bernard Feringa, spoke at Foresight’s 2013 Conference on “Molecular Rotary Motors“. A year ago in this blog we noted his demonstration of “One-directional rotation in a new artificial molecular motor“, and a post in October 2012 pointed to a review that included a description of a molecular car developed by Feringa. A post here from October 2006 pointed to an article from Prof. Feringa on “Making molecular machines work”. One of the earliest posts on this blog pointed to commentary by Feringa in Nature “In control of molecular motion”, which included commentary on Prof. Sauvage’s work on molecular muscles implemented by contraction and stretching of a linear rotaxane dimer.

We are not the only ones to see the 2016 Chemistry Nobel as a turning point for nanotechnology. CBC news blogger Bob McDonald compares this award to Michael Faraday’s discovery of electromagnetic induction “BLOG: Nanotechnology on the cusp: Bob McDonald“:

The Nobel Prize in Chemistry awarded this week for developments in nanotechnology heralds a new era in science, akin to the discovery of electromagnetic induction 185 years ago. And like electricity, nanotechnology could influence the world in dramatic ways, not even imaginable today. …

There have been revolutions in technology since people discovered that metals made better tools than stone, or that computer chips could calculate better than mechanical machines. These are exciting times to be alive at the beginning of what could be another powerful game changer in human achievement.

Another appreciation of the importance of molecular machines recognized by this Nobel comes from a post on The Week by Ryan Cooper (hat tip to Gayle Pergamit) “Why organic chemistry is awesome“:

… the recently awarded Nobel Prize in Chemistry affords a great opportunity to appreciate the subtleties of organic chemistry. It’s not about sweeping theories of reality or evolution, but instead about building up, through years of painstaking and elaborate work, new and astonishing ways to manipulate atoms and molecules that could change how we live our lives. …

It’s not entirely clear yet what you could do with this stuff. But as Richard Feynman pointed out in 1959, the eventual end goal is to be able to build things one atom at a time. This would be tremendously powerful. We could create new objects with incredible precision, which means far less waste. “Technology has never had this kind of precise control; all of our technologies today are bulk technologies,” explains The Foresight Institute. “We take a lump of something and add or remove pieces until we’re left with whatever object we were trying to create.” The rest gets tossed aside. No more with molecular manufacturing.

And imagine what we could do by sending tiny machines into hard-to-reach places. For example, the blood stream:

Theorists envision creating machines that will be able to travel through the circulatory system, cleaning the arteries as they go; sending out troops to track down and destroy cancer cells and tumors; or repairing injured tissue at the site of the wound, even to the point of replacing missing limbs or damaged organs. [The Foresight Institute]

There will surely be more applications to come, and with them, perhaps more well-deserved Nobel Prizes. And maybe chemistry will get its own household name, after all. But in the mean time, let us celebrate the marvels of this field and all it has to offer our future.

Foresight looks forward to covering how molecular machines and other technologies will eventually bring general purpose, high-throughput atomically precise manufacturing, and how this breakthrough will synergize with breakthroughs in biotechnology and medicine, artificial intelligence, and other rapidly developing transformative technologies to create a flourishing and and abundant future for humanity.
—James Lewis, PhD

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Assembling a large, stable, icosahedral protein molecular cage

The design model of the icosahedral nano-cage shows its large, empty volume. UW Institute for Protein Design

It feels like progress in the design and fabrication of atomically precise nanostructures and molecular machines is accelerating along several different paths. A couple days ago we cited advances in molecular machines fabricated using organic synthesis. Earlier this year we cited a number of advances along the protein design pathway to atomically precise manufacturing (here, here, here, here, here). A hat tip to Nanowerk for reprinting this recent advance from the University of Washington Health Sciences news room, written by Leila Gray, and describing work from the University of Washington Institute for Protein Design directed by David Baker, co-winner of the 2004 Feynman Prize, Theory categorySelf-assembling protein icosahedral shell designed“:

The same 20-sided solid that was morphed into geodesic domes in the past century may be the shape of things to come in synthetic biology.

For University of Washington Institute of Protein Design scientists working to invent molecular tools, vehicles, and devices for medicine and other fields, the icosahedron’s geometry is inspiring. Its bird cage-like symmetry and spacious interior suggest cargo-containing possibilities.

The protein designers took their cue from the many viruses that, en route to living cells, transport their genomes inside protective icosahedral protein shells. These delivery packages, termed viral capsids, are formed to be tough enough to withstand the trip, efficiently use storage room, and break apart to release their contents when conditions are right.

The researchers’ paper [abstract, full text PDF from Baker Lab] in the scientific journal Nature reports on their computational design and experimental testing of a highly stable icosahedral protein nano-cage. Engineered at the atomic level, this nano-cage can construct itself from biochemical building blocks and information encoded in strands of DNA.

After selecting the design for this icosahedral nano-cage through computer modeling, the researchers produced it in bacteria. Electron microscopy of the resulting icosahedral particles confirmed that they were nearly identical to the design model.

The leads on the project were Yang Hsia, a University of Washington graduate student in biological physics, structure and design, and Jacob B. Bale, a recent graduate from the UW molecular and cellular biology Ph.D. program, and now a research scientist at Arzeda Corporation in Seattle. The senior authors were Neil P. King, translational investigator at the UW Institute for Protein Design, and David Baker, director of the Institute and UW professor of biochemistry. Baker is also an investigator with the Howard Hughes Medical Institute.

“The ability to design proteins that self-assemble into precisely specified, robust, and highly order icosahedral structures,” the researchers wrote, “would open the door to a new generation of protein containers with properties custom-made for applications of interest.”

Among these applications might be fabricating nanoscale icosahedral vehicles. Such research might create tiny, spacecraft-like devices that could encapsulate and deliver therapies directly to specific types of cells, such as cancer cells.

The designed icosahedron, while sturdy, proved to disassemble and reassemble itself under certain environmental conditions. This reversible property is essential if it eventually becomes part of packaging, carrying and delivering a biochemical payload.

In addition, the flexibility to modify these miniature cages, the researchers said, “should have considerable utility for targeted drug delivery, vaccine design and synthetic biology.”

The newly designed icosahedron has considerably larger internal volume than previously designed nano-cages of other shapes, and so could hold more cargo as molecular shipping containers.

Working towards that end, the researchers were able to design barriers for the center of each of the twenty faces of the icosahedron. These could block molecules from entering and leaving the cage. In future iterations, gated cages might be filled to carry a medication into particular kinds of cell and then discharge it.

Moreover, the protein building blocks making up the cage retain their natural enzymatic activity, which is the ability to speed up chemical reactions. This suggests the possibility of custom designing them as nano-reactors to catalyze specific biochemical processes.

The nano-cages were, in addition, amenable to genetic fusions to enhance their properties. For example, the researchers created standard candles for light microscopy by adding a fluorescent protein to each of the 60 subunits that frame the icosahedron. The fluorescent intensity was proportional to the number of these proteins attached to each subunit. The distinctive shape of the icosahedron makes it a readily spotted marker.

The authors note that various approaches to designing proteins to self-assemble into complexes have often yielded polydisperse distributions including unanticipated products. Recently, more sophisticated modeling has generated tetrahedral and octahedral nanocages, but these are relatively small complexes, less than 16 nm in diameter, with limited internal volume. Trimeric protein scaffolds were designed to assemble with icosahedral symmetry, packing as closely as possible without steric clashes, and 17 designs selected for expression in bacteria and characterization. One design was selected that gave soluble protein that could be purified to yield a 60-subunit icosahedron. Further analysis showed a monodisperse population of particles with a hydrodynamic radius of 14 nm, consistent with the design model. The trimeric building block was stable to 80 °C and 6.7 M guanidine hydrochloride, but the icosahedron rapidly dissociates into the trimeric building blocks between 2 M an 2.25 M guanidinium thiocyanate. The disassembly is completely reversible upon decreasing the guanidinium thiocyanate concentration. Cryo-electron microscopy of the particles confirmed realization of the design goal of an icosahedron of 25 nm diameter and an interior volume of about 3000 nm3, comparable to small viral capsids. The ability to design precise and stable structures of such high internal volume is indeed impressive, despite the need to make and test a number of similar designs to accomplish the design goal.
—James Lewis, PhD

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Chemical fuel keeps molecular motor moving

Earlier this year we cited further progress on molecular machines, in this case transporting cargo, from the group of Professor David A Leigh FRS FRSE MAE and winner of the 2007 Feynman Prize in Nanotechnology, Theoretical category. Further molecular machine progress was recently reported by Belle Dumé at “Chemically powered nanomotor goes autonomous“:

Researchers at the University of Manchester, UK have made the first autonomous chemically powered synthetic small-molecule motor. The new device, which is very much like the protein motors found in biological cells, might be used to design artificial molecular machines similar to those found in nature. Such machines could be important for applications such as synthetic muscles, nano- and micro-robots and advanced mechanical motors.

Molecular machines are ubiquitous in nature and are at the heart of nearly every biological process. They have evolved over billions of years to exploit energy from sunlight or complex chemical reactions in the body, and are made up of complicated assemblies of proteins responsible for a host of processes in living organisms, such as ion transport, ATP synthesis and cell division.

“Our synthetic molecular motor works in a manner reminiscent of motor proteins, in which motion is powered by the protein catalyzing the hydrolysis of ATP,” explains team leader David Leigh. “Our molecular motor also runs using a chemical fuel, Fmoc-Cl, and it derives its energy by catalytically decomposing the fuel to dibenzofulvene and CO2.” …

The article continues by explaining that previous chemically-fueled molecular motors required several fuel molecules to be continuously fed in different steps, while this new motor, once it is given the fuel molecule, moves continuously around a molecular track until the fuel is exhausted. The article quotes Leigh explaining that the motor works as an ‘information ratchet’ in compliance with the second law of thermodynamics, and that this initial version is very inefficient but that he expects incremental improvements to lead to applications like transporting building blocks for molecular construction. The motors might also be used as power packs for molecular muscles, nanoscale robotics and molecular factories, to name but a few.

Also quoted is Fraser Stoddard of Northwestern University, winner of the 2007 Feynman Prize in Nanotechnology, Experimental category who was not involved in this work. He described this advance as an important proof-of-principle in a burgeoning field of scientific endeavour that is intellectually challenging and experimentally demanding in the extreme. Another key milestone on the long road to applications in molecular nanotechnology has been reached.

Addition of Fmoc-Cl causes the blue ring to continuously rotate in a clockwise direction around the cyclic track. The Fmoc-Cl is activated by the bulky pyridine catalyst and reacts with any free OH groups on the track to form the Fmoc carbonate. Contemporaneously Fmoc groups are slowly cleaved from the track by Et3N. The rate of addition of the Fmoc groups depends on the position of the ring on the track, whereas the rate of cleavage does not. This biases the direction of Brownian motion of the blue ring causing directional rotation of the motor components. Image credit: Leigh group, University of Manchester

The operation of this molecular motor is diagrammed and described on the Leigh Group web site “Cracking Nanomotor, Gromit!“:

Designing molecular motors is rarely an intuitive process because behaviour at the molecular level is often very different to what we observe in our ‘big’ world. … In the mechanical machines we are familiar with the parts (cogs, flywheels, pistons etc) do not move unless and until a force is applied to make them do so. At the molecular scale, however, molecules and their parts are constantly moving through Brownian motion and it is finding ways to control the directionality of that motion that is the key to developing working nanomachines. Now, scientists at the University of Manchester have invented a synthetic molecular motor that runs off chemical energy in a similar manner to the way that motor proteins use ATP (adenosine triphosphate) as a fuel …] In the man-made nanomotor, a synthetic molecular ring moves directionally around a molecular track powered by the motor’s catalysis of chemical reactions of a fuel. Remarkably, the motor mechanism depends on information transfer about the position of the ring to the track: when the ring is at the top of the track consumption of the fuel causes the motor to allow the ring to move faster to the right than to the left; when the ring is at the bottom of the track the motor allows the ring to move faster to the left than to the right. The net result is that the ring moves clockwise around the track as long as there is chemical fuel left for the motor to consume, just as a train can travel along a railway track until the diesel for its engine runs out.

The use of information transfer between molecular components to achieve directional motion in the motor mechanism is reminiscent of the Maxwell’s Demon thought experiment (although it requires more energy to be put in than is released and so does not challenge the Second Law of Thermodynamics!), a process that the Leigh group have previously used … to drive molecular systems away from equilibrium using light …

Continuing progress with molecular motors provides reason to be optimistic about the eventual development of atomically precise manufacturing and molecular robotics. We will eagerly await the next step forward.
—James Lewis, PhD

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Rational improvement of DNA nanodevice function

Left panel shows tweezers in the open position, with the enzyme (green) on the upper arm and the co-factor (gold) on the lower arm. Supplying a complementary fuel strand causes the tweezers to close, producing the reaction of the enzyme-cofactor pair. (Right panel) while a set strand restores the tweezers to their open position. Image credit: Biodesign Institute, Arizona State University

We have frequently cited examples of the artificial molecular machines that can be built from DNA. An open question is whether these prototype molecular machines can be improved toward practical applications. For example, can simple machines for manipulating molecules be improved to the point of implementing atomically precise manufacturing? A recent publication provides an example of rational improvement of a simple DNA machine reported three years ago. Three years ago a news release from the Biodesign Institute of Arizona State University reported “Tiny tweezers allow precision control of enzymes“:

Tweezers are a handy instrument when it comes to removing a splinter or plucking an eyebrow.

In new [2013] research, Hao Yan and his colleagues at Arizona State University’s Biodesign Institute describe a pair of tweezers shrunk down to an astonishingly tiny scale. When the jaws of these tools are in the open position, the distance between the two arms is about 16 nanometers—over 30,000 times smaller than a single grain of sand.

The group demonstrated that the nanotweezers, fabricated by means of the base-pairing properties of DNA, could be used to keep biological molecules spatially separated or to bring them together as chemical reactants, depending on the open or closed state of the tweezers.

In a series of experiments, regulatory enzymes—central components in a host of living processes—are tightly controlled with the tweezers, which can switch reactions on or off depending on their open or closed condition.

“The work has important implications for regulating enzymatic function and may help usher in a new generation of nanoscale diagnostic devices as well as aid in the synthesis of valuable chemicals and smart materials”, said Yan.

Results of the new research appear in the current issue of the journal Nature CommunicationsA DNA tweezer-actuated enzyme nanoreactor“. …

Enzymes are large molecules responsible for thousands of chemical interactions essential to life. A primary role for enzymes is to accelerate or catalyze myriad chemical reactions involved in processes ranging from digestion to DNA synthesis. To do this, enzymes lower the activation energy—the minimum energy needed for chemical reactions to occur—thereby speeding up the rate of such reactions. Enzymes are critical factors for health and disease, helping cells maintain their delicate homeostasis. When mutations lead to over- or under-production in certain key enzymes, severe genetic diseases—some of them, lethal—can result.

Because of the central importance of enzymes for biological systems, researchers want to gain a better understanding of how normal enzymatic reactions occur and how they may go awry. Such knowledge may encourage the development of techniques to mimic cellular processes involved in enzyme regulation.

In the current study, the authors create a nanoscale tool designed to manipulate enzymatic reactions with fine-grained control. The group dubs their device a tweezer-actuated enzyme nanoreactor.

The clever design separates an enzyme and a cofactor essential for successful reactions on separate arms of the tweezer-like instrument (See Figure 1). Enzyme function is inhibited when the tweezers are in their open position and the two molecules are held apart. Enzyme activation takes place when the tweezer prongs close, bringing enzyme and cofactor in contact. (The closing of the tweezers occurs when a specific DNA sequence is added, altering the thermodynamics of the system and causing a conformational change in the structure.)

The current study explores reactions in regulatory enzymes—multitasking entities that are important for modulating biochemical pathways. Regulatory enzymes, which can catalyze reactions over and over again, accomplish their feats by binding with biomolecular cofactors. (Hormone production and regulation are just one example of regulatory enzyme activity.)

In a series of experiments, the group was able to externally control the inhibition and activation of the enzyme through successive cycles. The authors stress that the nanoreactor tweezers could be used to regulate other types of enzymes and their control could be further refined by means of feedback and feed forward loops.

Engineering nanostructures from the bottom up, using DNA as a construction material, affords researchers exacting control over the resulting geometry. Previously, Yan has created nanostructures in two and three-dimensions, ranging from flat shapes to bowls, baskets, cages, Möbius strips and a spider-like autonomous walker.

In the tweezer design, a pair of 14 nm arms is connected at their ends by means of a 25 nucleotide single strand of DNA. This strand controls the opening and pinching of the tweezers, much the way a spring acts in a pair of gardening shears.

Two types of complementary sequence strand interact with this component, either forming a rigid DNA double helix, which supports the tweezers in their open position (set strands) or disabling the structural support and closing the tweezers, (fuel strands).

Two techniques were used to measure and analyze the resulting structures with nanoscale precision: Fluorescence Resonance Energy Transfer (FRET) and Atomic Force Microscopy (AFM). Experiments demonstrated a high yield for enzyme-bound tweezers, and successful switching between open and closed states was observed. The use of FRET allowed the process to be monitored in real time.

Lengthening the cofactor linker dangling from one of the tweezer’s arms enhanced successful opening and closing of the enzyme tweezers. Analysis revealed a 5-fold increase in enzymatic activity in the closed state compared with the open state. The study also demonstrated durability in the tweezers, which were able to cycle between the open and closed positions 9 times without losing structural integrity. The process was only limited by the accumulation of set strands and fuel strands.

Future work will explore similar responsive enzyme nanodevices capable of selective chemical amplification, with potentially broad impacts for medical diagnostics. Nanoreactors may also be applied as precision biocatalysts for the production of useful chemicals and smart materials.

The recent (2016) paper, from the Arizona State group working with groups from the University of Michigan and the Massachusetts Institute of Technology, endeavors to improve the relatively modest six-fold enhancement between open and closed tweezers positions seen in the first paper: “Rational design of DNA-actuated enzyme nanoreactors guided by single molecule analysis” (abstract, PDF made available by one of authors). To understand the structure-function relationships in the DNA tweezers, the authors combined molecular dynamics simulations with quantitative single molecule imaging using fluorescence resonance energy transfer (FRET) and atomic force microscopy (AFM). These experiments revealed two important deficiencies in the tweezers design: incomplete closure upon actuation, and conformational heterogeneity. Rational redesign of the DNA crossover motifs located in the hinge and arms regions led to more complete and more uniform closures.

FRET experiments with the initial tweezers designed showed one conformation in the open state, as expected, but two distinct conformations in the closed state, corresponding to distances between the two arms of > 10 nm and ~6.3 nm, respectively. Molecular dynamics simulations showed that incomplete closure was due to a flexible spacer of three thymidine residues. Eliminating the three-thymidine spacer, however, led to even less closure through the introduction of twisting between the arms of the tweezers. Switching to a one-thymidine spacer and re-designing the actuating hairpin by slightly extending the stem to increase stability improved performance, but did not eliminate heterogeneity.

Using the original enzyme plus cofactor activity assay to compare the original design with two of the above improved designs, one was found to be twice as active and the other three times as active. Single molecule observations suggest the presence of:

… two different mechanisms for improving nanoreactor performance: (i) a greater number of nanoreactors reach the critical [interarm] distance needed for activating their coupled enzyme with its cofactor due to improved closure upon optimized design of the actuator hairpin; and (ii) more frequent substrate turnover is achieved when stabilizing interarm tail–tail interactions are implemented that lead to straighter tweezer arms resulting from improved [Holliday junction] sequence design.

This research identified specific features of the original tweezers design that resulted in suboptimal performance and implemented a rational design strategy to improve each of two structural elements. The authors are confident that because the features identified here are general to many DNA nanostructures, they have established guidelines to rationally improving performance of a variety of nanodevices. It will be interesting to see how widely applicable these guidelines are, how far they can take performance improvement of various devices, and what new devices or systems such improvements make possible.
—James Lewis, PhD

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Atomically precise location of dopants a step toward quantum computers

An STM image showing the atomic level detail of the electron wave function of a sub-surface phosphorus dopant. Through highly precise matching with theoretical calculations the exact lattice site position and depth of the dopant can be determined. Credit: University of Melbourne

A couple months ago we cited the demonstration of a quantum simulator with dopant atoms placed in silicon with atomic precision. The same Australian and New Jersey teams have since further advanced the prospects for tomorrow’s silicon-based quantum computers. A hat tip to Nanowerk for reprinting this University of Melbourne news release “World-first pinpointing of atoms at work for quantum computers“:

Scientists can now identify the exact location of a single atom in a silicon crystal, a discovery that is key to greater accuracy in the operation of tomorrow’s silicon-based quantum computers.

It’s now possible to track and see individual phosphorus atoms in a silicon crystal allowing confirmation of quantum computing capability but which also has use in nano detection devices.

Quantum computing has the potential for enormous processing power in the future. Your current laptop has transistors that use a binary code, an on or off state (bits). But tomorrow’s quantum computer will use quantum bits ‘qubits’, which have multiple states.

Professor Lloyd Hollenberg, at the University of Melbourne and Deputy Director of the Centre for Quantum Computation and Communication Technology, led an international investigation on the fundamental building blocks of silicon based solid-state quantum processors.

His collaborators Professor Sven Rogge and Centre Director Professor Michelle Simmons [winner of the 2015 Foresight Institute Feynman Prize, Experimental] at the University of New South Wales, obtained atomic-resolution images from a scanning tunneling microscope (STM) allowing the team to precisely pinpoint the location of atoms in the silicon crystal lattice.

“The atomic microscope images are remarkable and sensitive enough to show the tendrils of an electron wave function protruding from the silicon surface. The theory is now visible, this is a world first,’ said Professor Hollenberg.

Lead author of the paper recently published in Nature Nanotechnology [abstract, PDF made available by authors], Dr Muhammad Usman from the University of Melbourne said: ‘The images showed a dazzling array of symmetries that seemed to defy explanation, but when the quantum state environment is taken into account, suddenly the images made perfect sense.’

The teams from University of Melbourne, UNSW and Purdue University USA are part of the world-leading research at the Centre focused on the demonstration of the fundamental building blocks of a silicon-based solid-state quantum processor.

The above research is an interesting confirmation of the synergistic relationships among nanotechnology, computation, and artificial intelligence. Nanotechnology in various stages of development is enabling the continual improvement of classical computer technology, while the beginnings of atomically precise nanotechnology—molecular nanotechnology—are providing promising paths to the development of much more powerful quantum computers. Improvements in computer technology enable accelerating advances in artificial intelligence. Both first principles computational nanotechnology and artificial intelligence are necessary to accelerate discovery and design in nanotechnology and other molecular sciences, including progress toward general purpose, high-throughput atomically precise manufacturing. The next in Foresight’s series of highly interactive, invitational workshops (energy 2014, medical applications 2015, energy 2016) will be Artificial Intelligence for Scientific Progress. See also this Facebook post.
—James Lewis, PhD

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Watching individual chemical bonds during a reaction

Identification of reactants, transient intermediates, and products in a bimolecular enediyne coupling and cyclization cascade on a silver surface by non-contact atomic force microscopy. The corresponding chemical structures are depicted below the nc-AFM images. Image credit: A. Riss, adapted from DOI: 10.1038/nchem.2506

One path to advanced nanotechnologies begins with using scanning probe microscopes (SPM) to make atomically precise surface modifications—see, for example p. xii of Productive Nanosystems: A Technology Roadmap. The more precisely the SPM tip can image and manipulate atoms on a surface, the more rationally this path can be planned and implemented. Some of the most impressive progress along this path has come from using noncontact-atomic force microscopy (NC-AFM), such as measuring individual chemical bonds using a carbon monoxide-functionalized tip. Now researchers have succeeded in seeing changes in bond configurations as an organic reaction is catalyzed on a surface. A hat tip to Nanowerk for reprinting this press release from the Max Planck Institute for the Structure and Dynamics of Matter “Viewing a catalytic reaction in action“:

To be able to follow and directly visualize how the structure of molecules changes when they undergo complex chemical transformations has been a long-standing goal of chemistry. While reaction intermediates are particularly difficult to identify and characterize due to their short lifetimes, knowledge of the structure of these species can give valuable insights into reaction mechanisms and therefore impact fields beyond the chemical industry, such as materials science, nanotechnology, biology and medicine. Now an international team of researchers led by Felix R. Fischer, Michael F. Crommie (University of California at Berkeley and Lawrence Berkeley National Laboratory), and Angel Rubio (Max Planck Institute for the Structure and Dynamics of Matter at CFEL in Hamburg and University of the Basque Country in San Sebastián) has imaged and resolved the bond configuration of reactants, intermediates and final products of a complex and technologically relevant organic surface reaction at the single-molecule level. The findings are published in the journal Nature Chemistry [abstract].

Chemical transformations at the interface between solid/liquid or solid/gaseous phases of matter lie at the heart of key industrial-scale manufacturing processes. Understanding the microscopic mechanisms of such surface-catalyzed organic reactions is a grand challenge for modern heterogeneous catalysis and its application to industrial-scale chemical processes. Competing pathways that lead to numerous intermediates and undesired side products often hamper investigation of the underlying reaction mechanisms of reactions in chemical technology, such as the transformation of crude feedstock into complex value-added chemicals at the surface of a heterogeneous catalyst bed. The precise structural identification of transient reaction intermediates can be particularly difficult due to their low concentrations in the sample stream.

In the present work, the chemical structures associated with different steps of a reaction cascade of enediyne molecules on a silver surface were imaged using noncontact atomic force microscopy (nc-AFM) with special functionalized tips (using a carbon monoxide molecule to enhance resolution). Identification of the precise bond configuration of the intermediate species has allowed determining the sequence of chemical transformations along the pathway from reactants via intermediates to end products and unraveling the microscopic mechanisms behind that intricate dynamical behavior. “It was striking to be able to directly measure and theoretically characterize the chemical structure of reaction intermediates in this complex system,” said Felix Fischer, Professor for Chemistry at the University of Berkeley California and co-lead author of the study.

“This is a huge step for chemical synthesis,” added co-lead author Angel Rubio, Director at the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg and Distinguished Professor for Physics at the University of the Basque Country. “However, we wanted to go deeper and understand why the intermediates are stabilized on the surface – this does not happen in solution.” A combination of extensive state-of-the-art numerical calculations with classic analytical models describing the kinetics of sequential chemical reactions has shown that it is not enough to consider the energy potential landscape (i.e. the energies of the species along the reaction pathway and the associated transformation barriers), but that energy dissipation to the substrate and changes in molecular entropy play a critical role for the stabilization of the intermediates. The surface, and in particular the interaction of molecular radicals with the surface, plays a key role for both, entropy and selective dissipation, highlighting fundamental differences of surface-supported reactions compared to gas-phase or solution chemistry.

“The fruitful collaboration between theory and experiment allowed us to identify the microscopic driving forces that govern the global reaction kinetics,” said Alexander Riss, first author of the study. Such detailed understanding constitutes a fundamental milestone in the analysis of chemical reactions that was achieved through the synergy between single-molecule visualization of chemical reactions and state-of-the-art high-performance computer modeling. By these means, many limitations of conventional ensemble averaging spectroscopic techniques are surpassed, and an unprecedented atomic-scale picture of the reaction mechanisms, driving forces and kinetics emerges. Such new insight may open countless of hitherto unexplored venues for the future design and optimization of heterogeneous catalytic systems, for the development of novel synthetic tools applied to carbon-based nanotechnology, as well as for biochemical and materials science applications.

The immediate and near-term application of this research is no doubt the design of better catalysts, but these methods may also speed the use of scanning probe tips to build increasingly complex atomic configurations on surfaces.
—James Lewis, PhD

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Engineered protein assembles molecules into atomically precise lattice

A buckyball, a sphere-like molecule composed of 60 carbon atoms shaped like a soccer ball. (Image credit: St Stev via / CC BY-NC-ND)

An important step as nanotechnology develops toward the ultimate goal of general purpose, high-throughput, atomically precise manufacturing is the use of molecules specifically designed to organize other molecules into precise orientations in space. Simple first steps would be to organize repeating lattices of one component to make novel functional materials; more complex further steps would be to precisely organize the multiple components of molecular machine systems. An early step in this process was reported this spring using a specially engineered protein. A hat tip to Nanowerk for reprinting this Dartmouth College news release “Researchers Create Artificial Protein to Control Assembly of Buckyballs“:

A Dartmouth College scientist and his collaborators have created an artificial protein that organizes new materials at the nanoscale.

“This is a proof-of-principle study demonstrating that proteins can be used as effective vehicles for organizing nano-materials by design,” says senior author Gevorg Grigoryan, an assistant professor of computer science at Dartmouth. “If we learn to do this more generally – the programmable self-assembly of precisely organized molecular building blocks — this will lead to a range of new materials towards a host of applications, from medicine to energy.”

The study appears in the journal in Nature CommunicationsProtein-directed self-assembly of a fullerene crystal” [OPEN ACCESS].

According to the U.S. National Nanotechnology Initiative, scientists and engineers are finding a wide variety of ways to deliberately make materials at the nanoscale – or the atomic and molecular level — to take advantage of their enhanced properties such as higher strength, lighter weight, increased control of light spectrum and greater chemical reactivity than their larger-scale counterparts.

Proteins are “smart” molecules, encoded by our genes, which organize and orchestrate essentially all molecular processes in our cells. The goal of the new study was to create an artificial protein that would self-organize into a new material — an atomically periodic lattice of buckminster fullerene molecules. Buckminster fullerene (buckyball for short) is a sphere-like molecule composed of 60 carbon atoms shaped like a soccer ball. Buckyballs have an array of unusual properties, which have excited scientists for several decades because of their potential applications. Buckyballs are currently used in nanotechnology due to their high heat resistance and electrical superconductivity, but the molecule is difficult to organize in desired ways, which hampers its use in the development of novel materials.

In their new research, Grigoryan and his colleagues show that their artificial protein does interact with buckyball and indeed does organize it into a lattice. Further, they determined the 3-dimensional structure of this lattice, which represents the first ever atomistic view of a protein/buckyball complex.

“Learning to engineer self-assembly would enable the precise organization of molecules by design to create matter with tailored properties,” Grigoryan says. “In this research, we demonstrate that proteins can direct the self-assembly of buckminsterfullerene into ordered superstructures. Further, excitingly, we have observed this protein/buckyball lattice conducts electricity, something that the protein-alone lattice does not do. Thus, we are beginning to see emergent material behaviors that can arise from combing the fascinating properties of buckyball and the abilities of proteins to organize matter at the atomic scale. Taken together, our findings suggest a new means of organizing fullerene molecules into a rich variety of lattices to generate new properties by design.”

The three high-resolution protein crystal structures presented here, respectively resolved to 0.167, 0.176, and 0.235 nm, reveal a protein lattice with C60 groups wedged between two helical protein segments. The authors suggest that binding of the protein motif to a C60 directs the organization of the protein units in the co-crystal. Perhaps a next step is to see if proteins can be designed to assemble C60 molecules into different lattice structures having different useful properties. It will be interesting to compare this approach using engineered proteins with approaches using DNA nanotechnology to organize nanoparticles into various crystal lattices.
—James Lewis, PhD

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Peptoid nanosheets assemble by different design rule

Snakes on a plane: This atomic-resolution simulation of a peptoid nanosheet reveals a snake-like structure never seen before. The nanosheet’s layers include a water-repelling core (yellow), peptoid backbones (white), and charged sidechains (magenta and cyan). The right corner of the nanosheet’s top layer has been “removed” to show how the backbone’s alternating rotational states give the backbones a snake-like appearance (red and blue ribbons). Surrounding water molecules are red and white. Image courtesy of Ranjan V. Mannige, Molecular Foundry, Berkeley.

The earliest proposal to “open a path to the fabrication of devices to complex atomic specifications” envisioned designing proteins to fold in predetermined ways. Over the years we have cited here numerous advances along this path, most recently here, here, here, here, and here. There has also been interest in polymers that are chemical cousins of proteins, for example, the peptoids, in which the side chains are appended to the nitrogen atom in the peptide bond joining the monomers, rather than to the alpha carbon atom, as is the case with proteins. Four years ago we cited a report of initial successes in the rational design of peptoids, speculated that it might be opening a path to advanced nanotechnology, but noted that their successful computer modeling had so far only produced structures composed of nine subunits. Now we can cite further work by a subset of that group reporting a peptoid nanosheet, two molecules thick but extending laterally for micrometers, based on a structural element not seen in the natural world. A hat tip to Nanowerk for reprinting this news release from the U.S. Dept.of Energy Office of Science “Understanding and Predicting Self-Assembly“:

To mimic complex natural proteins’ capabilities as sensors, catalysts, and more using synthetic materials that can withstand industrial conditions, scientists must first know how to finesse the building blocks they’ll use. Molecular Foundry staff worked with scientists to discover a new design rule that controls the way in which polymer building blocks adjoin to form the backbones that run the length of tiny biomimetic sheets.

Understanding the rules that govern how the nanosheets self-assemble could be used to piece together complex sheet structures and others, such as nanotubes and crystalline solids, that could be customized into incredibly sensitive chemical detectors or long-lasting catalysts, to name a few possibilities.

Scientists aspire to build nanostructures that mimic the complexity and function of nature’s proteins, but are made of durable and synthetic materials. These microscopic widgets could be customized into incredibly sensitive chemical detectors or long-lasting catalysts, to name a few possible applications.

But as with any craft that requires extreme precision, researchers must first learn how to finesse the materials they’ll use to build these structures. A recent discovery by scientists at the Molecular Foundry is a big step in this direction.

The researchers discovered a design rule that enables a recently created material to exist. The material is a peptoid nanosheet. It’s a flat structure only two molecules thick, and it’s composed of peptoids, which are synthetic polymers closely related to protein-forming peptides.

The design rule controls the way in which polymers adjoin to form the backbones that run the length of nanosheets. Surprisingly, these molecules link together in a counter-rotating pattern not seen in nature. This pattern allows the backbones to remain linear and untwisted, a trait that makes peptoid nanosheets larger and flatter than any biological structure.

The Molecular Foundry scientists say this never-before-seen design rule could be used to piece together complex nanosheet structures and other peptoid assemblies such as nanotubes and crystalline solids.

What’s more, they discovered it by combining computer simulations at National Energy Research Scientific Computing Center, another DOE user facility located at Berkeley Lab, with x-ray scattering and imaging methods to determine, for the first time, the atomic-resolution structure of peptoid nanosheets.

The research was reported in a paper published last fall in Nature [abstract]. Additional details are contained in a longer release from the Lawrence Berkeley Lab “Newly discovered ‘design rule’ brings nature-inspired nanostructures one step closer“:

“This research suggests new ways to design biomimetic structures,” says Steve Whitelam, a co-corresponding author of the Nature paper. “We can begin thinking about using design principles other than those nature offers.”

Whitelam is a staff scientist in the Theory Facility at the Molecular Foundry, a DOE Office of Science user facility located at Berkeley Lab. He led the research with co-corresponding author Ranjan Mannige, a postdoctoral researcher at the Molecular Foundry; and Ron Zuckermann, who directs the Molecular Foundry’s Biological Nanostructures Facility. They used the high-performance computing resources of the National Energy Research Scientific Computing Center (NERSC), another DOE Office of Science user facility located at Berkeley Lab.

Peptoid nanosheets were discovered by Zuckermann’s group five years ago. They found that under the right conditions, peptoids self assemble into two-dimensional assemblies that can grow hundreds of microns across. This “molecular paper” has become a hot prospect as a protein-mimicking platform for molecular design.

To learn more about this potential building material, the scientists set out to learn its atom-resolution structure. This involved feedback between experiment and theory. Microscopy and scattering data gathered at the Molecular Foundry and the Advanced Light Source, also a DOE Office of Science user facility located at Berkeley Lab, were compared with molecular dynamics simulations conducted at NERSC.

The research revealed several new things about peptoid nanosheets. Their molecular makeup varies throughout their structure, they can be formed only from peptoids of a certain minimum length, they contain water pockets, and they are potentially porous when it comes to water and ions.

These insights are intriguing on their own, but when the scientists examined the structure of the nanosheets’ backbone, they were surprised to see a design rule not found in the field of protein structural biology.

Here’s the difference: In nature, proteins are composed of beta sheets and alpha helices. These fundamental building blocks are themselves composed of backbones, and the polymers that make up these backbones are all joined together using the same rule. Each adjacent polymer rotates incrementally in the same direction, so that a twist runs along the backbone.

This rule doesn’t apply to peptoid nanosheets. Along their backbones, adjacent monomer units rotate in opposite directions. These counter-rotations cancel each other out, resulting in a linear and untwisted backbone. This enables backbones to be tiled in two dimensions and extended into large sheets that are flatter than anything nature can produce.

“It was a big surprise to find the design rule that makes peptoid nanosheets possible has eluded the field of biology until now,” says Mannige. “This rule could perhaps be used to build many more unrealized structures.”

Adds Zuckermann, “We also expect there are other design principles waiting to be discovered, which could lead to even more biomimetic nanostructures.”

Perhaps the most striking result from this work is the discovery that protein-like polymers can adopt secondary structures entirely unlike anything seen with natural proteins. The zigzag pattern that enables the formation of the nanosheet is termed by the authors a Σ (sigma) strand. The authors explain that the Σ strand results from the ability of adjacent monomers to rotate in opposite directions, while most elements of protein secondary structure are built from one rotational state. The authors note that this difference “might greatly expand the repertoire of folded polymeric building blocks.” They conclude taht this new building principle combined with a wide selection of chemically diverse monomers “offers a way to create new structured polymers through combinatorial design.”
—James Lewis, PhD

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