Supporting-role arrows
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Adapted from
“Mechanical Control of Spin States
in Spin-1 Molecules and the Underscreened Kondo Effect”
J. J. Parks et al., Science, 328:1370–1373 (2010).

Pulling on the ends of a cobalt complex that bridges an electrical junction (as illustrated) changes the geometry of the coordinating ligands, hence the energies of electronic spin states, hence (as it turns out) the low-temperature electrical resistance of the junction. The authors of the paper cited here look toward potential applications for devices that manipulate spin states mechanically:

…Our work further demonstrates that mechanical control can be a realistic strategy for manipulating molecular spin states to supplement or replace the use of magnetic fields in proposed applications such as quantum manipulation or information storage.
(Science,June 2010)

Whether or not their approach is practical, this paper is a reminder that almost all molecular properties are sensitive to mechanical effects, and sometimes in important ways. Modulating chemical reactivity and selecting among reaction sites are basic and obvious examples of molecular mechanical effects, but the general class can be anticipated to be as broad as the effects of temperature or pressure.

• Mechanochemistry, Mechanosynthesis, and Molecular Machinery
• The Physical Basis of Atomically Precise Manufacturing
• Productive nanosystems: the physics of molecular fabrication [pdf]
  (from the Institute of Physics journal, Physics Education)
• Molecular Nanomachines: Physical Principles and Implementation Strategies (from the Annual Review of Biophysics and Biomolecular Structure)

As regular readers know, I see foldamer engineering as a key to next-generation atomically precise nanosystems. Valuable in themselves, foldamers can also serve as components of composite systems that exploit diverse materials and nanotechnologies of qualitatively different kinds.

“Foldamers: Accomplishments and Goals”, by Samuel Gellman, heads a collection of 59 abstracts from a recent international conference on foldamers held in Bordeaux-Pessac, France. (Note that Gellman also authored the classic 1998 paper, “Foldamers: A Manifesto”.)

This set of abstracts offers a good window into the state of a broad, dynamic, and important field.

The Economist reports that “…a bright future beckons, and some of the nanohype that has been swirling around might actually get translated into a useful product.”

The reason is that “…adding a sprinkle of nanoparticles to water can improve its thermal conductivity, and thus its ability to remove heat from something that it is in contact with, by as much as 60%.” Measured by potential impact on cooling efficiency (cost, performance, energy consumption), this could be quite important.

Measured by fulfillment of the vast, free-floating promise of nanotechnology, though, I doubt that this application (based on a phenomenon “discovered almost two decades ago”) will be perceived as entirely satisfying.

How did nanotechnology garner such high public expectations — and support — long before either payoffs or a clear sense of what the research was all about? History, of course.

When I picked up my copy of this week’s Chemical & Engineering News this evening, I found that the lead article begins with this:

Futuristic visions of nanobots that travel the body to treat disease and construct compounds one atom at a time got a little closer to reality this week, thanks to two advances in nanoscale robotics reported in Nature (2010, 465, 202 and 206). Using DNA as the key construction material, one group of researchers created a nanoscale robot that can autonomously walk across a track, and a different group prepared a nanofactory in which DNA robots can carry and deposit nanoparticle cargo.

The article closes with this:

“A goal of our field is to refashion and reimagine all the complex biochemical machinery of cells to suit our own purposes—to have synthetic molecules that can move around and carry cargo as protein motors do in cells, to have molecules that act as chemical factories, which make a particular product based on a particular chemical input, and above all to make these processes modular, to make them engineerable,” notes Paul W. K. Rothemund, the Caltech scientist who invented DNA origami. “These two papers mark a significant advance along this research direction.”

This is great — I can quote C&EN instead of writing my own report of the news, and by the same stroke, this makes the C&EN report part of that news.

As a bonus, the wording of the C&EN report gives me an opportunity to remind readers that the idea of constructing things “one atom at a time” is based on a misconception, serving as a common but dangerous shorthand for “atomically precise fabrication”. The mistaken idea that these are equivalent has caused endless difficulties, because chemists recognize that juggling individual atoms makes no chemical sense.

To hammer the point again: Organic synthesis is already atomically precise, and works quite well without juggling individual atoms. The same holds for prospective methods of advanced mechanosynthesis.

And yes, what we see in Nature is a step in this direction.

AFM image, magnified
(Inset shows vertical magnification)

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Matterhorn, demagnified
(Original image in upper panel)

Text and graphics excerpted from Figure 4 of a recent paper on a new form of nanoscale lithography:

AFM scan of the replica of the Matterhorn written into the molecular glass
(3D data source: geodata © swisstopo).

The maximum steepness of slopes is an important parameter in scanning probe lithography. It would be easy to misread the original images.

Maat Mons is displayed in this three-dimensional perspective view of the surface of Venus, with the vertical scale multiplied by 22.5.
(from Wikipedia, with the rescaled right-hand panel added for entertainment value)

Self-assembled peptoid membranes, 2.7 nm thick

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“Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers”, K.T. Nam et al., Nature Materials (on web: April, 2010)

Fresh from Ron Zuckerman’s lab at the Molecular Foundry: a new kind of molecular membrane — thin and crystalline — made by self-assembly of peptoid oligomers. As I discussed in an earlier post, peptoids have remarkable potential as building blocks for self-assembled nanosystems. Peptoids are peptide-like structures, but with monomers that can be chosen from among thousands of readily-available building blocks (a broad class of primary amines). Some of my enthusiasm for peptoids came from an early peek at the results now reported in Nature Materials.

Reports of new nanoscale constructs turn up almost every day, and they often include claims of wondrous potential applications that are literally incredible. It’s refreshing to read a paper making bold claims like these —

The ability to efficiently create functionalized 2D crystals by spontaneous assembly will lead to many applications in device fabrication, nanoscale synthesis and imaging, membrane mimetics, sensors and separations. More generally, the ability to mimic protein architecture with synthetic polymers should eventually enable new families of robust artificial proteins with highly specific functionality.

— and to find them thoroughly credible.

News of the paper has been reported from the Berkeley Labs News Center, in Chemical & Engineering News, and at Wired.com.

Here’s view of an idealized sheet, looking across rows of chains with alternating positive and negative charge on the outer surfaces and hydrophobic phenethyl sidechains sandwiched between:

Note the modified chain at the lower right.

• Peptoids at the Molecular Foundry
• Modular Molecular Composite Nanosystems
• A Third Revolution in DNA Nanotechnology

Zinc fingers & DNA

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From “Toward Modular Molecular
Composite Nanosystems”
[talk slides, pdf]

Zinc finger technology has great promise in genetic engineering and therapeutics, with potential applications in structural DNA nanotechnology, too.

Zinc finger proteins (ZFPs) are often called “game changing” because of the unprecedented way they precisely modify genes. Excitement about them is mirrored in the number of related scientific publications, which have climbed from hardly any 20 years ago to more than 360 in 2009.

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Chemical & Engineering News

A ZFP is a sequence of small protein structures (the fingers) that, taken together, bind to a specific DNA sequence. Unlike oligonucleotides, which bind to the Watson-Crick interface of single-stranded DNA, ZFPs bind in the major groove of double-stranded DNA (dsDNA), recognizing DNA base pairs from the side. They’re modular and can be engineered to target sequences chosen by a designer.

This mode of binding enables sequence-specific interactions without prying DNA strands apart, a fundamental advantage in a biological context. Binding dsDNA also opens a range of potential applications in structural DNA nanotechnology because it provides a way to bind protein structures to a dsDNA scaffold at specific sites, and with relatively high rigidity. This is an enabler for the DNA/protein/special-structure approach to modular molecular composite nanosystems.

Each finger binds with a degree of specificity and affinity, but multiple fingers must be stitched together to achieve tight, high-affinity binding to unique sequences. This engineering problem is tractable. There’s an open-source Zinc Finger Consortium (and a zinc-finger design server), as well as a thriving biotechnology company with a fat patent portfolio, Sangamo BioSciences. Sangamo aims to to produce products for medicine.

ZFPs enable a clever trick for editing DNA: A nuclease that cuts dsDNA can be inactivated by splitting into domains that regain activity when brought together. The complementary domains are linked to ZFPs that bind DNA sequences flanking a target site. Where these sequences are found together, both ZFPs bind, bringing the nuclease domains together; these bind, regain function, and cut, leaving the rest of the genome untouched.

This synergistic, cleanly targeted operation can be leveraged to inactivate or edit a selected genetic component with unmatched reliability and specificity. Powerful applications follow.

Bioinformatics is huge, growing, fast, and has a surprising range of applications to molecular systems engineering. Here’s a PLoS article: “A Quick Guide for Developing Effective Bioinformatics Programming Skills”. From the abstract:

Successful adoption of these principals will serve both beginner and experienced bioinformaticians alike in career development and pursuit of professional and scientific goals.

See also:

• How to study for a career in nanotechnology
• Macromolecular Modeling for Molecular Systems Engineering
• How to Learn About Everything