Productive Nanosystems as a Milestone Toward Geoethical Nanotechnology
James B. Lewis, Ph.D.
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Recent progress
Computational demonstration of minimal toolset for diamond mechanosynthesis; major funding for experimental tip-based approaches
Robert A. Freitas Jr. and Ralph C. Merkle [25] published quantum chemistry calculations that analyzed a complete set of reaction pathways for performing diamond mechanosynthesis using scanning probe microscopes under high vacuum conditions. The calculations show that nine tools, starting with simple bulk chemical inputs, including flat, depassivated diamond and germanium surfaces, and using only four feedstock molecules, can, in sixty-five reaction sequences, fabricate all nine tools, including their handles, recharge all nine tools, and build a variety of diamond and graphene structures. The use of three elements (carbon, germanium, and hydrogen) provides a number of different bond strengths for targeted bond breaking. Energies, reaction pathways, and geometries were analyzed computationally for several hundred reaction steps and side reactions. This work constitutes the first comprehensive theoretical treatment of diamondoid mechanosynthesis.
Professor Philip Moriarty has received a five-year grant support to perform a series of laboratory experiments to test the reactions proposed by Freitas and Merkle [26] so the practicality of those proposals should become evident over the next few years.
Another consortium led by John Randall of Zyvex Labs was awarded a $9.7M grant from DARPA and the state of Texas [27] to investigate another ultra-high vacuum scanning probe microscope path to atomically precise manufacturing. This effort does not appear to be related to diamond mechanosynthesis, but rather begins with atomically precise depassivation of a silicon surface and follows the patterned atomic layer epitaxy route (above plus ref. [13]).
Complex atomically precise patterning on a surface achieved by purely mechanical forces
Vertical interchange between atoms on an atomic force microscope tip and a semiconductor surface enabled scientists to write the chemical symbol for silicon (Si) by individually depositing twelve silicon atoms on an atomic monolayer of tin atoms on a silicon surface, using only mechanical forces [28]. The experiments were done at room temperature and the vertical exchange of atoms between surface and tip was found to be about ten times faster than lateral manipulation of atoms on a surface that had been previously demonstrated; however, it still took 1.5 hours to build the pattern.
Protein catalysts designed for non-natural chemical reaction
Major steps have been taken toward the goal of the creation of enzymes capable of catalyzing any desired chemical reaction [29]. A group headed by Kendall Houk used quantum chemistry calculations to design the three-dimensional arrangement of chemical groups within a protein to catalyze any desired chemical reaction. Then a group headed by David Baker designed a sequence of amino acids to fold to give a protein with an active site like the one designed by Houk’s group. In an initial accomplishment, the researchers designed an enzyme called a retro-aldolase to break a carbon-carbon bond in a molecule that is not naturally a substrate for retro-aldolases. In a second paper, they designed an enzyme to catalyze a reaction that is not normally catalyzed in nature. The second paper marks a major milestone in computational chemistry and protein engineering, and is also a major milestone in the protein design path to APPNs.
Design from scratch of a simple, functional protein
Scientists have designed from scratch a simple, functional protein using principles discovered by studying natural proteins, but using those principles to design a simple, robust protein where most natural proteins are complex and fragile [30]. The approach used is a major departure from the usual method of protein engineering in which minor modifications are made to a natural protein in order to change its properties. Indeed, Eric Drexler, who has advocated a protein-engineering path toward advanced nanotechnology since a paper he published in 1981, hailed this research in a blog post as “A Revolution in de novo Protein Engineering” because “They advocate an engineering approach that explicitly rejects aspects of the biological model.” A fundamental idea behind this work is that evolution produces proteins that provide a needed function, but evolution does not necessarily produce structures that are convenient for engineering purposes. The usefulness of this research is not that they have engineered an artificial protein that binds oxygen as does hemoglobin, but that they succeeded in using basic engineering principles to build a simple, robust protein that worked despite lacking the complexity of natural evolved proteins.
Programming biomolecular self-assembly pathways to fabricate DNA constructs
Researchers led by Niles Pierce demonstrated the ability to program how DNA strands self-assemble and disassemble and in so doing were able to program a number of dynamical functions, including fabricating a DNA nanostructure to walk along a DNA track [31]. DNA strands containing three sequence motifs interact with other DNA strands containing complementary motifs in ways that are programmed according to which motifs on which strands are complementary. Changing the sequence relationships among the various motifs changes the structures that are formed by the strands and the functions that those structures can execute. The long-term goal is to input a molecular program that will output a set of DNA molecules that will execute the desired function.
Advances in DNA building blocks and programmed assembly
A number of results herald the appearance of DNA molecular building blocks that could be useful for building more complex and functional DNA nanostructures. Extending earlier work in which DNA “fuel” strands had been used to cause movement in DNA nanostructures and in which rigid tetrahedrons were built from DNA, Andrew Turberfield and colleagues have built DNA tetrahedrons that change shape when fuel strands are added [32]. Such structures could act as motors in nanoscale robots, and the researchers are working on using these components to build larger structures.
A team led by Chengde Mao has devised a simple DNA building block that self-assembles to form larger three-dimensional DNA nanostructures [33]. They modified a simple three-point star motif that had previously been used as a tile to form flat two-dimensional crystals. By introducing a variable amount of flexibility into the motif and controlling the concentration of the tiles, the tiles could be made to self-assemble into tetrahedra, dodecahedra, or buckyballs containing four, twenty, or sixty individual tiles. The researchers “expect that our assembly strategy can be adapted to allow the fabrication of a range of relatively complex three-dimensional structures.”
A team led by Günter von Kiedrowski used DNA strands to assemble an atomically precise building block (a six-carbon aromatic ring) into atomically precise nanoparticles [34]. Previous work using DNA strands to program the assembly of nanoparticles did not yield atomically precise nanoparticles. In this case twenty structures were synthesized in which three 15-nucleotide long DNA sequences were attached to a 6-member aromatic ring with DNA sequences designed such that when the twenty structures were mixed together they aggregated to form a regular dodecahedron.
Peng Yin and colleagues developed a simple modular approach to programming the diameter of DNA nanotubes so that a "Single-step annealing results in the self-assembly of long tubes displaying monodisperse circumferences of 4, 5, 6, 7, 8, 10 or 20 DNA helices." [35] Erik Winfree and Paul W.K. Rothemund and their colleagues demonstrated that DNA origami structures can serve as seeds to program the construction of nanotech structures up to 100 times larger [36].
Additions to the DNA molecular recognition code and polymer backbone
The great strength of structural DNA nanotechnology is the ease of programming the four-letter molecular recognition code provided by the two Watson-Crick base pairs. A group headed by Floyd E. Romesberg has expanded the DNA alphabet with a third base pair [37]. Unlike earlier additional base pairs that had been devised, this one works with at least one of the enzymes that replicate DNA, which might help when using test tube evolution to produce DNA molecules with specific molecular recognition or catalytic properties.
A group led by Masahiko Inouye developed a stable analog of DNA in which the two Watson-Crick base pairs are replaced by two other base pairs, and the bases are connected to the sugar-phosphate background by a different type of chemical linkage [38].
An alternative to the 5-carbon sugar-phosphate backbone of DNA has been developed by John Chaput and colleagues using the 3-carbon glycerol molecule [39]. Four-helix junction nanostructures (a basic structure of structural DNA nanotechnology) built using this glycerol nucleic acid (GNA) were more stable to temperature than were comparable structures made from DNA, and they were easily made in both left- and right-handed forms—which is not the case with DNA.
Footnotes
[25] Robert A. Freitas Jr. and Ralph C. Merkle “A Minimal Toolset for Positional Diamond Mechanosynthesis” Journal of Computational and Theoretical Nanoscience
Vol.5, 760–861, 2008. http://www.molecularassembler.com/... [accessed Apr. 1, 2009].
[26] “Nanofactory Collaboration Colleague Awarded $3M to Conduct First Diamond Mechanosynthesis Experiments” http://www.MolecularAssembler.com/... [Press Release August 11, 2008; web site accessed Apr. 1, 2009].
[27] “Zyvex-led Atomically Precise Manufacturing Consortium...” Zyvex press release from PRnewswire, posted on Nanodot Oct. 8, 2008.
[28] "Complex patterning by vertical interchange atom manipulation using atomic force microscopy" Yoshiaki Sugimoto, Pablo Pou, Oscar Custance, Pavel Jelinek, Masayuki Abe, Ruben Perez, Seizo Morita. Science 322: 413-417 (2008). Abstract. See also the Nanodot post by Jim Lewis on November 6th, 2008 “Mechanosynthesis with AFM as a step toward...” and the blog post “AFM Atom Manipulation: A surprising technique” by Eric Drexler on March 14, 2009.
[29] The research is described in a press release from UCLA written by Stuart Wolpert “'Designer enzymes' created by chemists at UCLA, U. of Washington” The first paper was published in Science and the second in Nature. “De novo computational design of retro-aldol enzymes” Lin Jiang, Eric A. Althoff, Fernando R. Clemente, Lindsey Doyle, Daniela Röthlisberger, Alexandre Zanghellini, Jasmine L. Gallaher, Jamie L. Betker, Fujie Tanaka, Carlos F. Barbas, III, Donald Hilvert, Kendall N. Houk, Barry L. Stoddard, David Baker. Science 319: 1387-1391 (2008). Abstract. “Kemp elimination catalysts by computational enzyme design” Daniela Röthlisberger, Olga Khersonsky, Andrew M. Wollacott, Lin Jiang, Jason DeChancie, Jamie Betker, Jasmine L. Gallaher, Eric A. Althoff, Alexandre Zanghellini, Orly Dym, Shira Albeck, Kendall N. Houk, Dan S. Tawfik & David Baker. Nature 453: 190-195 (2008). Abstract. For comments on the relevance to nanotechnology, see Nanodot post by Jim Lewis on March 25, 2008 “Major nanotechnology milestone...”.
[30] The research is described in a University of Pennsylvania press release “Proteins by Design...”. The research was published in Nature. "Design and engineering of an O2 transport protein" Ronald L. Koder, J. L. Ross Anderson, Lee A. Solomon, Konda S. Reddy, Christopher C. Moser & P. Leslie Dutton. Nature 458: 305-309 (2009). Abstract.
[31] The research is described in a Caltech news release “Programming Biomolecular Self-Assembly Pathways” and in a New Scientist article by Robert Adler “DNA 'fabricator' constructs walking DNA”. The research was published in Nature. "Programming biomolecular self-assembly pathways" Peng Yin, Harry M. T. Choi, Colby R. Calvert & Niles A. Pierce. Nature 451: 318-322 (2008). Abstract.
[32] The results are described in a New Scientist article by Tom Simonite “Remote-control DNA 'pistons' could power tiny robots”. The research was published in Nature Nanotechnology. "Reconfigurable, braced, three-dimensional DNA nanostructures" Russell P. Goodman, Mike Heilemann, Sören Doose, Christoph M. Erben, Achillefs N. Kapanidis & Andrew J. Turberfield. Nature Nanotechnology 3: 93-96 (2008). Abstract.
[33] The research was published in Nature. "Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra" Yu He, Tao Ye, Min Su, Chuan Zhang, Alexander E. Ribbe, Wen Jiang & Chengde Mao. Nature 452: 198-201 (2008). Abstract. The results were discussed by Roger Highfield, Science Editor of the Telegraph (UK) “DNA building blocks five billionths of a metre across created” and by Jim Lewis in Nanodot “Simpler way of building...”.
[34] The research is described in press release from Wiley-Blackwell, via AAAS EurekAlert “Nanosoftball made of DNA: Programmed' oligonucleotides with 3 branches organize themselves into dodecahedra”. The research was published in Angewandte Chemie International Edition, but no abstract is available. Citation.
[35] The results are described at nanotechweb.org, written by Belle Dumé (requires free registration) “DNA tubes control their size“. The research was published in Science, “Programming DNA Tube Circumferences” Peng Yin, Rizal F. Hariadi, Sudheer Sahu, Harry M. T. Choi, Sung Ha Park, Thomas H. LaBean, John H. Reif. Science 321: 824-826 (2008). Abstract. The complete paper is available from Erik Winfree's lab, in which the work was done:
http://www.dna.caltech.edu/Papers/Peng_SST_2008.pdf
[36] The results were discussed in New Scientist, written by Colin Barras “DNA origami comes to life“. The research was published in the Proceedings of the National Academy of Sciences. "An information-bearing seed for nucleating algorithmic self-assembly" Robert D. Barish, Rebecca Schulman, Paul W. K. Rothemund and Erik Winfree. Published online before print March 24, 2009 (abstract). The full text (1.6 MB PDF) is free via Open Access.
[37] The research was published in the Journal of the American Chemical Society. "Discovery, Characterization, and Optimization of an Unnatural Base Pair for Expansion of the Genetic Alphabet" Aaron M. Leconte, Gil Tae Hwang, Shigeo Matsuda, Petr Capek, Yoshiyuki Hari, and Floyd E. Romesberg. Journal of the American Chemical Society 130: 2336-2343 (2008). Abstract. The results are discussed in a New Scientist article by Robert Adler "Artificial letters added to life's alphabet" and by Jim Lewis on Nanodot “A new base pair for DNA nanotechnology”.
[38] The research was published in the Journal of the American Chemical Society. "Artificial DNA Made Exclusively of Nonnatural C-Nucleosides with Four Types of Nonnatural Bases" Yasuhiro Doi, Junya Chiba, Tomoyuki Morikawa and Masahiko Inouye. Journal of the American Chemical Society 130: 8762–8768. Abstract. The results are described in ScienceDaily "First DNA Molecule Made Almost Entirely Of Artificial Parts".
[39] The results were described in a news release from Arizona State University, via AAAS EurekAlert "Scientists make chemical cousin of DNA for use as new nanotechnology building block". The research was published in the Journal of the American Chemical Society. "Synthesis of Two Mirror Image 4-Helix Junctions Derived from Glycerol Nucleic Acid" Richard S. Zhang, Elizabeth O. McCullum and John C. Chaput. Journal of the American Chemical Society 130: 5846–5847 (2008). Abstract.