1. Matthew Mancuso BEE 7600, Professor Dan Luo Department of Biomedical Engineering, Cornell University Presented Thursday February 17 th, 2011 “Give me a lever long enough… and I shall move the world.” --Archimedes of Syracuse Nucleic Acid Nanomachines and the Reimagined Red Blood Cell Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell,"Artificial Cells, Blood Substitutes, and Immobil. Biotech. 26(1998):411-430 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 shor t

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

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

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

5. 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) One of the first examples of a DNA nanomachine Changes between two states indefinitely Uses DNA for fuel, produces an inert byproduct

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 Jonathan Bath & Andrew J. Turberfield. DNA nanomachines. Nature Nanotechnology 2, 275 - 284 (2007) 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

8. Rotating Motors 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 Two states, one is rotated Uses two set and unset strands Uses DNA for fuel, produces an inert byproduct

9. Simple Logic Circuits 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

10. Using DNA to make Artifical RBCs “Molecular sorting rotors can be designed from about 10 5 atoms (including the housing), measuring roughly 7 nm x 14 nm x 14 nm…” Exploratory Theoretical Design Actual Design 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. Where are we headed? A synthesis of techniques 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 Bottom Up Design Top Down Design Chemistry DNA Nanotechnology Nanopatricles Material Science LithographyEtchingMicrofluidicsImprintingEngineering

12. Thanks… And check my website for these Presentations!