Productive Nanosystems as a Milestone Toward Geoethical Nanotechnology
James B. Lewis, Ph.D.
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S. W. Bishnoi and D. S. English [18] briefly summarize the advantages of proteins for atomically precise manufacturing (they combine well-defined secondary and tertiary structure with a wide range of side chain chemical functionality) and the prospects for engineering proteins specifically suited for atomically precise manufacturing. For example, a phage display library, in which mutations in a virus coat protein are selected that bind to some target material, can be used for the combinatorial selection of peptides with the highest affinity for some selected nanoscale material, which can then be used to control crystal formation of that material, or for biomimetic self-assembly approaches to APM. The de novo design of proteins using software such as the ROSETTA program developed by the Baker group opens the way to designing proteins with specific binding properties to help create MMCNs. Particularly interesting are tools to combine various zinc finger peptides found in natural proteins to produce artificial proteins with high affinity for specific DNA sequences.
D.G. Allis [19] describes several broad topics from synthetic chemistry relevant to changing covalent bonds and forming new building blocks for more complex nanostructures. The foundation of chemical synthesis is organic synthesis, which involves the stable and highly localized bonds between carbon and (usually) hydrogen, oxygen, and nitrogen, and which extends the range of molecular assembly beyond what is allowed by the chemical conditions in living organisms, either by using non-biological chemical environments or non-biological chemical building blocks. Extending the capabilities of organic synthesis depends on developing new reaction pathways and mechanisms, a process that will be aided by improvements in isolating and identifying reaction intermediates, and by new theoretical insights. One route to increased control of the chemical environment lies in encapsulating reacting molecules using dendrimers, coordination complexes, or molecular capsules.
C. E. Schafmeister [20] describes a pathway from current technology to productive nanosystems that depends on the development of designed catalysts that function similarly to biological enzymes. The proposal aims to produce a concentrated liquid solution of a few hundred to a few thousand designed catalysts that would resemble the cytoplasm of a cell, but would be controlled by a desktop computer using electrical impulses and oxidation-reduction chemistry to activate the catalysts. Achieving this second generation nanotechnology first requires the ability to rationally design catalysts and molecular recognition. Developing these first generation nanotechnology abilities begins with a new molecular building block technology that—compared with natural amino acids and proteins— enables easier design and affords more diverse chemical functionality. The basis of this new technology is bis-peptides, which are cyclic monomers that link via pairs of bonds instead of single peptide bonds (as do proteins) to create well-defined 3D shapes instead of relying on a complex folding process (as to proteins). Thus bis-peptides provide a systematic approach to building molecules with programmed shapes because they can be linked together to build rigid ladder molecules with designed shapes. More than a dozen bis-amino acid building blocks have been synthesized, and they can be assembled by standard solid-phase peptide synthesis methodology. The result of the second bond between each pair of bis-amino acid monomers is a bis-peptide oligomer with no rotatable bonds within its core structure so that its shape is simply and directly determined by the sequence of its building blocks. Currently under development is a general synthesis method that would yield bis-amino acid building blocks that carry an even wider array of chemically functional side chains than do amino acids. These could be used to produce bis-peptides with more diverse chemical functionally than found in proteins.
The hope is that these advantages of bis-peptides will lead to the ability to synthesize “macromolecules in which we can control where almost every atom goes in three-dimensional space.” This ability will in turn lead to designed catalysts—macromolecules of 5000 to 100,000 Daltons in which several chemically reactive groups are positioned in three-dimensional space so as to catalyze a chemical reaction. Smaller catalysts could be prepared by solid phase synthesis, but accessing the upper end of this size range will require the ability to create rigid, covalent networks from several bis-peptide oligomer modules. In one scheme for doing this, each module would contain several monomer side chain functional groups designed to anchor the modules together into a specific three-dimensional shape. Other functional groups in each module would then be positioned in three-dimensional space to guide the chemical reaction to be catalyzed.
J. Youell and K. Firman [21] review the variety of molecular motors provided by biology that might be adapted for use in APM. These include the rotary motor that packs DNA into the head of a virus and the rotary motor that drives the flagella that enable bacteria to swim (which provides an example of a complex machine that self-assembles from about forty proteins at the site at which it is needed). Examples of linear motors include the motor protein myosin that powers muscle contraction and the kinesins and dyneins that transport cargoes along the microtubule networks within eukaryotic cells. Other motors use DNA as their linear track, or pull DNA through a molecular complex. The ATP Synthase motor uses a membrane bound motor powered by proton flux across the membrane to rotate a second motor that uses that mechanical force to synthesize ATP molecules, the energy currency of the cell. In principle, this rotation could be used to do work in a nanodevice. Similarly, kinesin motors have been harnessed to transport microtubules across etched surfaces—perhaps leading to a way of transporting material between different regions on a work surface. DNA translocases, which pull DNA through a molecular complex, are proposed as a “conveyor belt” component of an artificial ribosome, which would pull building blocks arranged along a DNA molecule in a programmed sequence past an assembly site, at which they would be linked together.
To the list of feasible molecular motors and mechanical devices provided by biology, D. R. Forrest, R. A. Freitas Jr., N. Jacobstein [22] add consideration of individually addressable electrical nanoactuators, bearings, and springs built from multi-walled carbon nanotubes. They also review molecular motors and other devices activated by light that have been used to provide mechanical motion. They conclude from their survey that artificial systems and biology provide a wide range of molecular machines, but progress toward using these motors in useful ways will require advances in standardizing device fabrication to achieve uniform results, integrating devices and components “to perform more complex nanomechanical operations”, and moving from surface to three-dimensional arrangements of components.
Options for the path forward
Emerging from the Technology Roadmap for Productive Nanosystems is a compelling survey of the technologies available to develop advanced molecular manufacturing systems. This collection of starting technologies is interdisciplinary in the extreme, encompassing surface physics, materials science, various fields of chemistry, biological and non-biological polymers, molecular biology, and biotechnology—not to mention computational, simulation, and design efforts. Consideration of the strengths and weaknesses of different starting technologies suggests developing a tip-based approach based upon manipulating atoms and molecules on surfaces using scanning probe microscopes, and a bio-based approach in which various types of polymers are used to construct frameworks on which diverse functional components can be organized. The tip-based approach encompasses several different uses of scanning probe microscope tips. Most simply, they could be used for atomically precise removal of passivating atoms from a surface followed by crystal growth on the vacancies that result to build small atomically precise parts. They could be used for manipulating molecular building blocks under gentle conditions conducive to solution chemistry. Or they could be used under high vacuum conditions with extremely reactive species for diamond mechanosynthesis.
The roadmap envisions combining a bio-based approach of building modular molecular composite nanosystems, with possible use of small parts of high performance materials built beginning with tip-based depassivation of a surface, or of molecular building blocks manipulated by scanning probe tips under solution-phase chemistry conditions. Tip-based and bio-based approaches would be combined, and increasingly more reactive components would be used, eventually leading to advanced systems incorporating diamond mechanosynthesis under machine-phase chemistry conditions. Since the publication of the roadmap, the modular molecular composite nanosystems path continues to be elaborated by K. Eric Drexler [23].
An alternate viewpoint [24] advocates starting with scanning probe microscopes under high vacuum conditions to directly develop diamond mechanosynthesis as a faster route to mature molecular manufacturing systems.
In an ideal world all feasible paths toward molecular manufacturing would be developed in parallel until it became clear how best to proceed. Furthermore, progress in all of the enabling technologies would be continuously monitored and the roadmap would be updated and refined as new results made more detailed plans sensible. In the absence of comprehensive monitoring of progress, we offer here a brief survey of significant advances during the past year and a half since the completion of the roadmap. Taken together, the following advances demonstrate that the “direct to diamond” proposal is making substantial progress, and that the modular molecular composite nanosystem is progressing rapidly on several fronts. Nevertheless, the quest to build advanced molecular manufacturing systems that could bring us technological immortality and take us to the stars is only beginning. Much more work will be required to make the path come into focus.
Footnotes
[18] S. W. Bishnoi and D. S. English “Protein Bioengineering Overview” pp. 10-1 to 10-4 in Working Group Proceedings (see [11] above).
[19] D.G. Allis “Synthetic Chemistry” pp. 11-1 to 11-6 in Working Group Proceedings (see [11] above).
[20] C. E. Schafmeister “A Path to a Second Generation Nanotechnology” pp. 12-1 to 12-21 in Working Group Proceedings (see [11] above).
[21] J. Youell and K. Firman “Biological Molecular Motors for Nanodevices” pp. 22-1 to 22-18 in Working Group Proceedings (see [11] above).
[22] D. R. Forrest, R. A. Freitas Jr., N. Jacobstein “Molecular Motors, Actuators, and Mechanical Devices” pp. 23-1 to 23-8 in Working Group Proceedings (see [11] above).
[23] “Modular Molecular Composite Nanosystems” by Eric Drexler on Nov. 10, 2008. http://metamodern.com/2008/11/10/modular-molecular-composite-nanosystems/ [accessed Apr. 1, 2009] and subsequent posts at http://metamodern.com/. See “Peptoids at the Molecular Foundry”, “Molecular Assembly Lines”, “Toward Advanced Nanosystems: Materials (2)”, “From Self-Assembly to Mechanosynthesis”, “Toward Advanced Nanotechnology: Nanomaterials (3)”.
[24] Robert A. Freitas Jr. and Ralph C. Merkle: “Our assessment is that diamondoid mechanosynthesis (DMS), including highly-parallelized atomically-precise diamondoid fabrication, is the quickest currently feasible route to a mature molecular nanotechnology, including nanofactories. We do not think that DMS is a ‘necessary first step’ for molecular manufacturing, and we wish the best of luck to those pursuing other paths. However, we do think DMS is a highly desirable first step, since it offers a much faster route to mature nanosystems than competing approaches. We disagree with the statement that ‘diamond synthesis seems almost irrelevant to progress toward advanced nanosystems.’ We have a favorable view of the feasibility of the direct-to-DMS approach – a favorable view supported by hundreds of pages of detailed analysis in recently-published peer-reviewed technical journal papers and by gradually-evolving mainstream opinion.”
http://www.molecularassembler.com/Nanofactory/ [comment dated Dec. 28, 2008 and web site accessed Apr. 1, 2009].