Researchers Find ‘Goldilocks’ Of DNA Self-Assembly

It turns out that this particular protocol can work if the strand lengths are chosen carefully.  Not something that would ever be obvious.

Advancing the art is now a practical proposition, though actual applications are still a long ways off.  Certainly the possibility of protecting a drug until it arrives at a treatment site does suggest itself and is well worth the effort.  As we become more precise in our understanding of biological issues, this approach for drug delivery will become even more plausible.

Now it would be nice to design something around an anti malarial toxin that is benign until it encounters the parasite itself.

Researchers Find ‘Goldilocks’ Of DNA Self-Assembly
For Immediate Release
Matt Shipman | News Services | 919.515.6386
Dr. Yaroslava Yingling | 919.513.2624

Researchers from North Carolina State University have found a way to optimize the development of DNA self-assembling materials, which hold promise for technologies ranging from drug delivery to molecular sensors. The key to the advance is the discovery of the “Goldilocks” length for DNA strands used in self-assembly – not too long, not too short, but just right.

This image is a simulation snapshot of the molecular dynamics of DNA strands.
DNA strands contain genetic coding that will form bonds with another strand that contains a unique sequence of complementary genes. By coating a material with a specific DNA layer, that material will then seek out and bond with its complementary counterpart. This concept, known as DNA-assisted self-assembly, creates significant opportunities in the biomedical and materials science fields, because it may allow the creation of self-assembling materials with a variety of applications.

But, while DNA self-assembly technology is not a new concept, it has historically faced some significant stumbling blocks. One of these obstacles has been that DNA segments that are too short often failed to self-assemble, while segments that are too long often led to the creation of deformed materials. This hurdle can lead to basic manufacturing problems, as well as significant changes in the properties of the material itself.

A team of researchers from NC State and the University of Melbourne have proposed a solution to this problem, using computer simulations of DNA strands to identify the optimal length of a DNA strand for self-assembly – and explaining the scientific principles behind it (see video below).

“Strands that are too short or long form self-protected motifs,” says Dr. Yara Yingling, an assistant professor of materials science and engineering at NC State and co-author of a paper describing the research. That means that the strands bond to each other, rather than to  “partner” materials.

“The optimal lengths are not long enough to intertwine with each other, and are not short enough to fold over on themselves,” Yingling explains. That leaves them exposed, and available to bond with the materials in another layer – the perfect situation for DNA self-assembly.

One potential application for such self-assembling materials is the development of drug-delivery vehicles. For example, researchers at the University of Melbourne have created self-assembling DNA capsules that are fully biocompatible, biodegradable and capable of releasing the drug when they come in contact with a specific physical stimulus – making them ideal for drug delivery.

DNA self-assembly technology is also expected to facilitate the creation of molecular sensors that use DNA to detect, and signal the presence of, clinically important biological molecules – which could have significant diagnostic applications in the medical field.

“We’re now planning to explore additional factors that play a role in DNA self-assembly,” Yingling says, “including temperature, genetic sequence and the environment in which the assembly takes place.”

The paper, “Effect of Oligonucleotide Length on the Assembly of DNA Materials: Molecular Dynamics Simulations of Layer-by-Layer DNA Films,” was published online Oct. 12 by the journal Langmuir. Lead author of the paper is Abhishek Singh, a Ph.D. student at NC State. Co-authors include Yingling; former NC State post-doctoral research associate Dr. Stacy Snyder; and Drs. Frank Caruso, Lillian Lee and Angus Johnston of the University of Melbourne. The work was supported by funding from NC State and the Australian Research Council.
Note to Editors: The study abstract follows.
“Effect of Oligonucleotide Length on the Assembly of DNA Materials: Molecular Dynamics Simulations of Layer-by-Layer DNA Films”
Authors: Abhishek Singh, Stacy Snyder, Yaroslava G. Yingling, North Carolina State University; Lillian Lee, Angus P.R. Johnston, Frank Caruso, The University of Melbourne
Published: online Oct. 12, 2010, Langmuir
Abstract: DNA strand length has been found to be an important factor in many DNA-based nanoscale systems. Here, we apply molecular dynamics simulations in a synergistic effort with layer-by-layer experimental data to understand the effect of DNA strand length on the assembly of DNA films. The results indicate that short (less than 10 bases) and long (more than 30 bases) single-stranded DNAs do not exhibit optimal film growth, and this can be associated with the limited accessibility of the bases on the surface due to formation of self-protected interactions that prevent efficient hybridization. Interestingly, the presence of a duplex attached to a single strand significantly alters the persistence length of the polyT strands. Our study suggests that restrained polyT, compared to labile suspensions of free polyT, are more capable of hybridization and hence DNA-based assembly.

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