The basics of DNA nanotechnology.
Introduction:
Today I’ll be talking about an interesting concept in modern biochemistry, which is leveraging the intrinsic biochemical and physical properties of deoxyribonucleic acid (DNA) sequences to make synthetic DNA nanostructures. Typically, most people think of DNA as the molecule which contains our unique genetic codes for life. Therefore, DNA is often thought of in terms of genes, mutations, and phenotypes. However, DNA can be also be considered as a programmable biopolymer composed of monomers known as nucleotides. The interactions between nucleotides are extremely predicable based on the Watson-Crick-Franklin base pair rules. By using customized sequences, specific information and behavior can be programmed directly into the DNA itself. This idea is what forms the basis DNA nanotechnology and has led to the inception of cutting edge concepts in the field.
One such concept is DNA origami. DNA origami is a technique where a long “scaffold” strand can be folded into nearly any arbitrary 3-D geometry through the interaction of many small “staple” strands. Using DNA origami, nanometer sized structures resembling writing [1], smiley faces [2], and even the Mona Lisa [3] have been fabricated .
Another interesting concept is encoding digital data into DNA sequences for secure data storage. For instance, each nucleotide in a DNA sequence can store 2 bits of information. Thus by synthesizing custom DNA strands digital information can be logically encoded. This is currently a HOT topic in the field because the information density of DNA is astronomically high. For example, the Escherichia coli bacteria genome has an information storage density of approximately 1.25 exabytes of data per cubic cm. For perspective, if this density could be industrially implemented, the entire digital information content of the world in 2017 (~1 zettabyte) could fit into a 10 by 10 by 10 cm cube [4, 5]. On this scale, 5 times that amount of data could fit into a standard US large egg.
These are just a couple highlighted examples but there are many other interesting applications of DNA origami nanostructures such as for nanophotonic and plasmnonic applications [6], drug delivery [7], computing [8], and fabricating dynamic DNA nanomachines [9]. But in order to fully understand these topics, DNA itself needs to be understood. Below I am just going to give a brief and general overview of DNA and what it is.
DNA Basics:
As previously mentioned, DNA can be thought of as a polymer composed of nucleotide monomers. Each nucleotide is composed of a nitrogenous base conjugated to a deoxyribose sugar at the 1’ carbon through a glycoside bond (Figure 1 Left).
The 5’ hydroxyl of the deoxyribose can be phosphorylated allowing the polymerization reaction to occur. In this reaction the the 3’ hydroxyl of another nucleotide reacts with the 5' phosphate forming the phosphodiester bond (Figure 2 Circles). This 3’-5’ phosphodiester bond connection forms what is known as the sugar-phosphate backbone and ultimately is what defines a DNA polynucleotide.
The specificity of DNA arises from the four distinct nitrogenous bases and the Watson-Crick-Franklin base pair rules. The rules state a pyrimidine (guanine [G] & adenine [A]) will principally bind a purine (cytosine [C] & thymine [T]) with the specific ruleset; A binds to T and G binds to C. When two strands with complementary sequences are mixed in aqueous buffer and thermally annealed, they bind and spontaneously from a B-form double helix (Figure 3). The B-form helix is generally what people envision when they think of the typical DNA helix but there are other rare helices such as A- and Z-form DNA. Here it becomes clear how Figures 1 and 2 fit together and form the alpha helix.
Some general characteristics of B-form helices are; a base-to-base distance of about 0.34 nm along a single strand, about 10.5 bases (~3.4 nm) per helical turn, a helical diameter of about 2 nm, and about a 147 base (~50 nm) persistence length.
Parting Words:
These hybridization rules and the B-form DNA helix have been known since the early 1950s [10] and forms the physcial basis of DNA nanotechnology. The theoretical framework wasn’t initially pioneered until the 1980s when the late Nadrian Seeman exploited the partial complementarity of sequences to conjoin helices and form nucleic acid lattices which could be united into larger 2- and 3-dimensional architectures [11]. Since then, modern techniques such DNA origami and open-source software such as CaDNAno [12] have made the fabrication of nearly arbitrary DNA geometry both simple and accessible.
I’m traveling this weekend so this article is a very quick and general primer to the basics of DNA nanotechnology. The idea is that this post will be a reference for future posts on more specific applications of DNA nanotechnology such as DNA computing or DNA digital data storage. So if you are interested in these topics, stay tuned.
