Matthew Mancuso BEE 7600, Professor Dan LuoDepartment of Biomedical Engineering, Cornell University Presented Thursday February 17th, 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

short

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 Body Carbon Dioxide from Body to Lungs

Nucleic Acid Nanomachine Toolsand How We Can Use ThemWhy

Nucleic Acids?

Putting DNA to Work

Here Be Dragons…

A Nucleic Acid Nanomachine Toolbox

Tweezing WalkingRotating Switching

Base Pair Matching

DNA Machines and RBCs

The next Steps

“Biology has at least 50 more

interesting years…”

--James Watson

Why DNA Nanomachines?Sequence Specificity is the KEY

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 G3’ 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 G3’ 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

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

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)

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

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

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

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…”

Exploratory Theoretical DesignActual 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

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

ChemistryDNA

NanotechnologyNanopatricles

Material Science

LithographyEtching

MicrofluidicsImprinting

Engineering

Thanks…And check my website for these Presentations!