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DNA Blueprints Guide The Construction Of Specific Human Structures Print E-mail
SciMed - Biology
TS-Si News Service   
Monday, 04 February 2008 20:00
DNA Blueprints Guide The Construction Of Specific Human Structures.Evanston, IL, USA. DNA is the blueprint of all life, containing instructions and giving function to organisms ranging from simple one-celled bacteria to complex human beings. Scientists devote a great deal of research attention to the underlying mechanisms that lead to developmental success. Fully understanding how this process works is essential to exploring the basis for variation, whether disease or birth conditions, such as intersex and Harry Benjamin Syndrome (HBS).
 
The relevant DNA research studies encompass many life science disciplines, such as biology, chemistry, genetics, genomics, neuroscience, and others. However, research in other fields (such as computer science, information theory, mathematics, nanotechnology, and physics) can illuminate basic questions in the life sciences.
 
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For example, findings from otherwise unrelated research efforts in materials science can offer insight into how the DNA blueprint is applied in practice and suggests some directions for research.
 
Findings from a seemingly unrelated research effort in materials science can offer insight into how the DNA blueprint is applied in practice and suggests some directions for research.The actions of very small particles can have large implications for scientists dealing with biological processes or the construction of new materials. A nanoparticle is so small it is measured at the miscroscopic scale. The basic unit of measurement, the nanometer (nm), is one billionth of a meter — equivalent to 10 ångström (Å). A particle so tiny can be an aggregate of anywhere from a few hundred to tens of thousands of atoms. However, the particles are large enough for combination into crystalline forms.
 
Nanoparticle research is currently an area of intense scientific activity, due to a wide variety of potential applications in biomedical, optical, and electronic fields. Particles at the nanoscale often are used in biomedical applications, acting as drug carriers or imaging agents. The processes that underlie how these aggregates form can span biological and inanimate materials.
 
Self-assembly is an important process in which a disordered system of pre-existing components forms an organized structure or pattern. This organization takes place among the components themselves as a consequence of specific and local interactions. Once the environment is established and kept stable, there is no external direction. 
 
Computer rendition of a structure created by using DNA to assemble nanoparticles into well-defined crystal lattices. Source: Northwestern University.
Computer rendition of a structure created by using DNA to assemble nanoparticles into well-defined crystal lattices.
Image courtesy of Northwestern University.
Now researchers from Northwestern University report they have used DNA as the blueprint, contractor and construction worker to build a three-dimensional structure out of a lifeless material (gold).
 
Using just one kind of nanoparticle (gold) the researchers built two common but very different crystalline structures by merely changing one thing — the strands of synthesized DNA attached to the tiny gold spheres.
 
A different DNA sequence in the strand resulted in the formation of a different crystal.
 
The technique, published in the journal Nature, reflects more than a decade of work. It is a major and fundamental step toward building functional "designer" materials using programmable self-assembly.
 
This "bottom-up" approach will allow scientists to take inorganic materials and build structures with specific properties for a given application, such as therapeutics, biodiagnostics, optics, electronics or catalysis.
 
Most gems, such as diamonds, rubies and sapphires, are crystalline inorganic materials. Within each crystal structure, the atoms have precise locations, which give each material its unique properties. Diamond's renowned hardness and refractive properties are due to its structure — the precise location of its carbon atoms.
 
In the Northwestern study, gold nanoparticles take the place of atoms. The novel part of the work is that the researchers use DNA to drive the assembly of the crystal. Changing the DNA strand's sequence of As, Ts, Gs and Cs changes the blueprint, and thus the shape, of the crystalline structure. The two crystals reported in Nature, both made of gold, have different properties because the particles are arranged differently.
 
Chad A. Mirkin. Photo by Bill Arsenault.Chad A. Mirkin

Mirkin is a senior author and George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences. He serves as professor of medicine, and professor of materials science and engineering.

Here, Mirkin discusses using DNA to build a three-dimensional structure out of gold, likening the process to building a house.

Starting with basic materials such as bricks, wood, siding, stone and shingles, a construction team can build many different types of houses out of the same building blocks.

Photo courtesy of the UCSD School of Medicine.
"We are now closer to the dream of learning, as nanoscientists, how to break everything down into fundamental building blocks, which for us are nanoparticles, and reassembling them into whatever structure we want that gives us the properties needed for certain applications," said Mirkin.
 
By changing the type of DNA on the surface of the particles, the team can get the particles to arrange differently in space. The structures that finally form are the ones that maximize DNA hybridization. DNA is the stabilizing force, the glue that holds the structure together. "These structures are a new form of matter," said Mirkin, "that would be difficult, if not impossible, to make any other way."
 
In the Northwestern work, DNA controls where the building blocks (gold nanoparticles) are positioned in the final crystal structure, arranging the particles in a functional way. The DNA does all the heavy lifting instead of the researchers. 
 
Using the extremely brilliant X-rays produced by the Advanced Photon Source synchrotron at Argonne National Laboratory in combination with computational simulations, the research team imaged the crystals to determine the exact location of the particles throughout the structure. The final crystals have approximately 1 million nanoparticles.
 
Mirkin, Schatz and their team just used one building block, gold spheres, but as the method is further developed, a multitude of building blocks of different sizes can be used — with different composition (gold, silver and fluorescent particles, for example) and different shapes (spheres, rods, cubes and triangles). Controlling the distance between the nanoparticles is also key to the structure's function. "Once you get good at this you can build anything you want," said Mirkin, director of Northwestern's International Institute for Nanotechnology
 
George C. Schatz, Northwestern University, Morrison Professor of Chemistry, directed the work."The rules that govern self-assembly are not known, however," said Schatz, "and determining how to combine nanoparticles into interesting structures is one of the big challenges of the field." Schatz, the Morrison Professor of Chemistry, directed the work. 
 
The Northwestern researchers started with gold nanoparticles (15 nanometers in diameter) and attached double-stranded DNA to each particle with one of the strands significantly longer than the other. The single-stranded portion of this DNA serves as the "linker DNA," which seeks out a complementary single strand of DNA attached to another gold nanoparticle.
 
The binding of the two single strands of linker DNA to each other completes the double helix, tightly binding the particles to each other. Each gold nanoparticle has multiple strands of DNA attached to its surface so the nanoparticle is binding in many directions, resulting in a three-dimensional structure — a crystal. One sequence of linker DNA, programmed by the researchers, results in one type of crystal structure while a different sequence of linker DNA results in a different structure.
 
"We even found a case where the same linker could give different structures, depending on the temperatures at which the particles were mixed," said Schatz.
 
"It took scientists decades of work to learn how to synthesize DNA," said Mirkin. "Now we've learned how to use the synthesized form outside the body to arrange lifeless matter into things that are useful, which is really quite spectacular." 
 
AuthorsIn addition to Chad A. Mirkin and George C. Schatz, other authors are Sung Yong Park, a former postdoctoral fellow in Schatz's lab and now at the University of Rochester (lead author); graduate student Abigail K. R. Lytton-Jean, Northwestern University; Byeongdu Lee, Advanced Photon Source, Argonne National Laboratory; and Steven Weigand, Northwestern's DND-CAT Synchrotron Research Center at Argonne's Advanced Photon Source.
CitationDNA-programmable nanoparticle crystallization. Sung Yong Park, Abigail K. R. Lytton-Jean, Byeongdu Lee, Steven Weigand, George C. Schatz & Chad A. Mirkin. Nature 451: 553-556 (31 January 2008). doi: 10.1038/nature06508.

First Paragraph

It was first shown more than ten years ago that DNA oligonucleotides can be attached to gold nanoparticles rationally to direct the formation of larger assemblies. Since then, oligonucleotide-functionalized nanoparticles have been developed into powerful diagnostic tools for nucleic acids and proteins, and into intracellular probes and gene regulators. In contrast, the conceptually simple yet powerful idea that functionalized nanoparticles might serve as basic building blocks that can be rationally assembled through programmable base-pairing interactions into highly ordered macroscopic materials remains poorly developed. So far, the approach has mainly resulted in polymerization, with modest control over the placement of, the periodicity in, and the distance between particles within the assembled material. That is, most of the materials obtained thus far are best classified as amorphous polymers, although a few examples of colloidal crystal formation exist. Here, we demonstrate that DNA can be used to control the crystallization of nanoparticle–oligonucleotide conjugates to the extent that different DNA sequences guide the assembly of the same type of inorganic nanoparticle into different crystalline states. We show that the choice of DNA sequences attached to the nanoparticle building blocks, the DNA linking molecules and the absence or presence of a non-bonding single-base flexor can be adjusted so that gold nanoparticles assemble into micrometre-sized face-centred-cubic or body-centred-cubic crystal structures. Our findings thus clearly demonstrate that synthetically programmable colloidal crystallization is possible, and that a single-component system can be directed to form different structures.
 
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