Dr. Nadrian Seeman received a B.S. in Biochemistry and a Ph.D. in Biological Crystallography. He has published over 200 papers. He presented a talk entitled “It’s more than the secret of life: Building with DNA”.
Seeman lamented that he is a working scientist, and therefore his work does not progress as fast as he would like it to. Some of the ideas he has had from the 1980’s still have not come to pass, but he is okay with that.
DNA is such great material that it has out-rivaled all the competition as the material used for genes. Reciprocal exchange, where DNA exchanges pieces of itself with another molecule in order to come up with a new strain takes place in the double helical context. Sequence symmetry is minimized through the use of branched junctions which can be used in 5, 6, 8, and 12 arm junctions. Twenty-seven years after the beginning of his work, Seeman is still working on a good crystal in order to use his theory regarding DNA crystallography. DNA comes with its own set of assembly instructions known as sticky end cohesion which utilizes hydrogen bonding. The structure of the molecule dictates where certain proteins are in the DNA. The central concept of structural DNA nanotechnology is combining branched DNA with sticky ends to make objects, lattices, and devices, using DNA as bricks and mortar or just as mortar. Seeman would like to be able to architecturally control scaffolding, as well as make nanotech devices. Currently crystallography is primarily guess work and is not as successful as it could be. If scientists could better organizing biological macromolecules they could create nano-electric components.
Why would we use DNA? The two key reasons are predictable molecular interactions and designing the shape by selecting a sequence. Seeman’s lab would like to control the structure of matter in 3D to the highest resolution possible so as to understand the ways that matter interacts with matter in the macro- and micro-scales
Xing Wang has come up with 8 and 12 arm junctions. These connected lattices may derive a variety of shapes. The requirements of lattice design components include:
- predictable interactions
- predicable local product structures
- structural integrity
Seeman has been able to create 2D, 2X arrays that look similar to rotini pasta. Robust arrays of DX triangles were devised by Boaquin Ding around 1996. When there are two of the arrays, they can be arranged to from large parallelograms and larger arrays in 2D. The lesson learned has been that DX cohesion is much more robust than a double sticky end. Many “wild” motifs can be configured this way in 2D.
Progress towards 3D arrays has advanced in the last few years. The best so far has been 3D trigonal DX lattices using X-ray diffraction in 10 angstrom resolution. The original tensegrity triangle shows an over-under motif, but the resolution is still along 10 angstroms although why this is the case is still unknown.
Chemistry can be diversified using nylon-DNA. The basic idea is using DNA to control molecular topography. The first base they made took about seven years to create and the second one took about four, so there is hope, Seeman said, that they may make the third one while he is still alive. The structure of the shortest piece of nylon is dictated by the DNA; two motifs can organize nanoparticles known as DNAzyme in 5 to 10 nm particles.
From genes to machines: using nano devices
A B-Z device has been configured using B and Z DNA, each of which is either left-handed or right-handed. However, the device does not take advantage of the strengths of DNA.
A sequence dependent device, on the other hand, does make use of the strengths of DNA when ordered in a particular sequence. This system is much more robust than the previously mentioned system. The device is connected to DNA trapezoid, and there is evidence for its viability by rearranging orientation.
Translation using nanomachinery in a ribosome like device
Translation introduced diversity into the RNA world, so DNA nanotech may make this a possibility in controlled conditions.
When in doubt, DNA is far more robust and better controlled than RNA. DNA, for many purposes, may also not be the best material to use, but it is great for prototyping these things to see if we can create these self assembly features anyway. DNA is still the easiest to use. It is easy to design and acquire, and the parameters are easier to maintain.