Nucleic Acid Nanomachines and the Reimagined Red Blood Cell

1. Nucleic Acid Nanomachines and the Reimagined Red Blood Cell short “Give me a lever long enough… and I shall move the world.” --Archimedes of Syracuse Matthew Mancuso BEE 7600, Professor Dan Luo Department of Biomedical Engineering, Cornell University Presented Thursday February 17th, 2011 Artist’s Rendering of a Respirocyte, a theoretical artificial red blood cell designed by Robert A. Freitas Jr.exploring the limits of what molecular nanotechnology could create Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell,"Artificial Cells, Blood Substitutes, and Immobil. Biotech.26(1998):411-430

2. Red Blood cells are “simple” nanomachines… they have only a few critical functions Oxygen from Lungs to Body Carbon Dioxide from Body to Lungs What is an artificial red blood cell... ...and why is he talking about it? This makes them an excellent candidate for exploratory design… Let’s see if we can do it better using DNA!

3. Why Nucleic Acids? Base Pair Matching Nucleic Acid Nanomachine Toolsand How We Can Use Them “Biology has at least 50 more interesting years…” --James Watson A Nucleic Acid Nanomachine Toolbox Tweezing Walking Rotating Switching Putting DNA to Work DNA Machines and RBCs Here Be Dragons… The next Steps

4. Sequence Specificity is the KEY to Nucleic Acids application in nanomachinary Why DNA Nanomachines? 3’ A T G C A T G C A T G C A T C C 5’ T A C G T A C G T A C G + 5’ T A C G T A C G T A C G T A G G More base pairs binding is thermodynamically favorable 3’ A T G C A T G C A T G C A T C C 5’ T A C G T A C G T A C G T A G G + 5’ T A C G T A C G T A C G The more bases that bind, the higher the affinity… using this we can engineer multiple “states” into DNA systems

5. Nucleic Acid Tweezers One of the first examples of a DNA nanomachine Changes between two states indefinitely Uses DNA for fuel, produces an inert byproduct Bernard Yurke, Andrew J. Turberfield, Allen P. Mills, Jr, Friedrich C. Simmel & Jennifer L. Neumann. A DNA-fuelled molecular machine made of DNA. Nature 406, 605-608 (10 August 2000)

6. Nucleic Acid Tweezers Bernard Yurke, Andrew J. Turberfield, Allen P. Mills, Jr, Friedrich C. Simmel & Jennifer L. Neumann. A DNA-fuelled molecular machine made of DNA. Nature 406, 605-608 (10 August 2000)

7. Stepping Motors DNA Fuels walking action Can be used to move a specific number of cycles, and a specific distance Can carry cargo Uses DNA for fuel, produces an inert byproduct Jonathan Bath & Andrew J. Turberfield. DNA nanomachines. Nature Nanotechnology 2, 275 - 284 (2007)

8. Rotating Motors Two states, one is rotated Uses two set and unset strands Uses DNA for fuel, produces an inert byproduct H Yan, X Zhang, Z Shen & N C Seeman. A robust DNA mechanical device controlled by hybridization topology. Nature 415, 62-65 (3 January 2002) N C Seeman. From genes to machines: DNA nanomechanical devices. Trends in Biochemical Sciences.Volume 30, Issue 3, March 2005, Pages 119-125

9. Simple switches form the basis for computation If you can build a NAND gate, you can form a full computer Can provide signal processing without ever converting to electronic Simple Logic Circuits

10. Actual Design Exploratory Theoretical Design Using DNA to make Artifical RBCs “Molecular sorting rotors can be designed from about 105 atoms (including the housing), measuring roughly 7 nm x 14 nm x 14 nm…” Y Tian and C Mao. Molecular Gears: A Pair of DNA Circles Continuously Rolls against Each Other. J. Am. Chem. Soc. 2004, 126, 11410-11411

11. Top Down Design Bottom Up Design Where are we headed?A synthesis of techniques Chemistry DNA Nanotechnology Nanopatricles Material Science Lithography Etching Microfluidics Imprinting Engineering Y Tian and C Mao. Molecular Gears: A Pair of DNA Circles Continuously Rolls against Each Other. J. Am. Chem. Soc. 2004, 126, 11410-11411

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