DNA : B uilding B locks of N anotechnology Alexander Powers B S J “A friend of mine suggests a very interesting possibility for relatively small machines. He says that, although it is a very wild idea, it would be interesting in surgery if you could swallow the surgeon. You put the mechanical surgeon inside the blood vessel and it goes into the heart and ‘looks’ around...it find out which valve is faulty and takes a little knife and slices it.” Richard Feynman offered this prophetic vision at his famous 1959 Caltech lecture “There’s Plenty of Room at the Bottom” – a seminal event in the history of nanotechnology. In developing nanoscale machines, Feynman suggested scientists take a hint from biology. After all, proteins zip around cells on elaborate transport systems while DNA molecules encode vast quantities of information on a molecular scale. Feynman asked innovators to, “consider the possibility that we too can make an object that maneuvers at that level”(Feynman, 1960). Little did he know that biology would be the key to making his vision a tangible reality nearly 50 years later. The burgeoning field of DNA nanotechnology -- using nucleic acids as a building material in an nonbiological context -- has recently yielded some incredible breakthroughs ranging from programmable drug delivery capsules to enzyme “spiders” and chemical logic gates. DNA nanotechnology has the potential to finally realize the nano-surgeon. Deoxyribonucleic acid (DNA) makes for an extremely effective building material at the nanoscale; afterall, nucleic acids are life’s information storage molecule of choice. Nearly everyone learns about uses four different kinds of nucleotides with different chemical structures: adenine, guanine, thymine, and cytosine. The sequence of these nucleotides describes the information available for “building” an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. Two strands of DNA pair up according to certain rules dictated by the molecular geometry of each nucleotide. Thymine pairs with adenine and cytosine pairs with guanine. This base pairing specificity is the foundation of designing DNA nanostructures. The key to building small is encoding the assembly information into the molecules themselves rather than using external forces to arrange them. Early successes often relied on these outside forces like atomic force microscopy or scanning tunneling microscopy to build structures molecule by molecule - approaches which cannot be easily scaled up to create large, complex structures (Shankland, 2009). The main advantage of DNA as a building material is that it can spontaneously self assemble, the sequence of nucleotides can be precisely controlled and the 3D structure is well understand (in contrast to the complexity of proteins). DNA nanostructures fall into one of two categories: structural and dynamic. Static structures are fixed arrangements of DNA in specific shapes. A variety of strategies exist to do this, one of the most successful of which is DNA origami. Dynamic structures are formed similarly but are designed to move using techniques like strand displacement - this is essential for any sort of computational or mechanical functionality. “Deoxyribonucleic acid (DNA) make for an extremely effective building material at the nanoscale” DNA by the time they graduate middle school - and with good reason. Just as computers derive vast amounts of information from a simple code of 1’s and 0’s stored electronically, DNA encodes the vast complexity of life in simple chemicals. Deoxyribonucleic acids are composed of long strands of repeating subunits known as nucleotides. DNA In a 2006 Nature article, Paul Rothemund coined the fanciful term “DNA Origami” to describe his successful manipulation of DNA strands into a variety of shapes. He synthesized six different shapes including squares, triangles, and five-pointed stars consisted of flat lattices of DNA. His revolutionary technique utilized a single long “scaffold” strand of 6 • B erkeley S cientific J ournal • S ynthetics • S pring 2014 • V olume 18 • I ssue 2