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Using DNA Information to Control the Structure of Matter in 3D Nadrian C. Seeman Department of Chemistry New York University New York, NY 10003, USA [email protected] DNA-Based Nanotechnology: Construction, Mechanics and Electronics Technische Universität Dresden May 11, 2009

Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

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Page 1: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Using DNA Information to Control theStructure of Matter in 3D

Nadrian C. Seeman

Department of ChemistryNew York University

New York, NY 10003, [email protected]

DNA-Based Nanotechnology:Construction, Mechanics and Electronics

Technische Universität DresdenMay 11, 2009

Page 2: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26
Page 3: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

DNA BASE PAIRS

C C

N

C

C

O

NH

O R

H

CH3

T

H

CC

NC

N C

N

N N

H

HC

H

R

A

O

C C

N

N

C

C

R

H

HN

H

H

C

C

NC

C

N

N

C

O

C

H

NR

H

N H

H

G

3.4 Å

~20 Å

B-DNA

DNA Is a Nanoscale Object

Reciprocal Exchange:A Theoretical Biokleptic Tool To Generate

New DNA Motifs

Seeman, N.C. (2001), NanoLett. 1, 22-26.

ReciprocalExchange

Resolve

Page 4: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Reciprocal Exchange in aDouble Helical Context

Seeman, N.C. (2001), NanoLett. 1, 22-26.

+

+Strand

Polarity

Identical

Strand

Polarity

Opposite Resolve

Reciprocal

Exchange

Resolve

Reciprocal

Exchange

DS + DS HJ

Biological Reciprocal Exchange:The Holliday Junction

1 4

2 3

1 4

2 3

1 24 3

1 4

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I

I I

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Page 5: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Seeman, N.C. (1982), J. Theor.Biol. 99, 237-247.

Design of Immobile Branched Junctions:Minimize Sequence Symmetry

I IACTCGTGC

TGAGCACG

••••••••

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C

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Wang, Y., Mueller, J.E., Kemper, B. & Seeman, N.C. (1991), Biochemistry 30, 5667-5674.Wang, X. & Seeman, N.C. (2007), J. Am. Chem. Soc. 129, 8169-8176.

5-Arm, 6-Arm, 8-Arm and 12-Arm Junctions

Page 6: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Bricks from the Ming Tombs in Nanjing

Page 7: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Sticky-Ended Cohesion: Smart Affinity

Qiu, H., Dewan, J.C. & Seeman, N.C. (1997) J. Mol. Biol. 267, 881-898.

Sticky-Ended Cohesion: Structure

Page 8: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Seeman, N.C. (1982), J. Theor.Biol. 99, 237-247.

The Central Concept of Structural DNA Nanotechnology:Combine Branched DNA with Sticky Ends to

Make Objects, Lattices and Devices

AB'

B

A'

A

B ' B'

B

A

A'

A'

B

OBJECTIVES AND APPLICATIONSFOR OUR LABORATORY

ARCHITECTURAL CONTROL AND SCAFFOLDING

[1] MACROMOLECULAR CRYSTALLIZATION (PERIODIC IN 2D AND 3D).[2] NANOELECTRONICS ORGANIZATION (PERIODIC IN 2D AND 3D).[3] DNA-BASED COMPUTATION (APERIODIC IN 2D OR 3D).[4] CONTROL OF POLYMER AND MATERIALS COMPOSITION & TOPOLOGY.

[1] NANOROBOTICS.[2] NANOFABRICATION.

NANOMECHANICAL DEVICES

SELF-REPLICABLE SYSTEMS

Page 9: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

NO

CRYSTALS?PRAY FOR CRYSTALSSET UP CRYSTALS

GUESS NEW CONDITIONS

GUESS CONDITIONS

CHANGE DEITIES

DO CRYSTALLOGRAPHY

YES

CURRENT CRYSTALLIZATION PROTOCOL

Seeman, N.C. (1982), J. Theor.Biol. 99, 237-247.

A New Suggestion for Producing Macromolecular Crystals

Page 10: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Robinson, B.H. & Seeman, N.C. (1987), Protein Eng. 1, 295-300..

A Method for Organizing Nano-Electronic Components

Robinson, B.H. & Seeman, N.C. (1987), Protein Eng. 1, 295-300.

A Suggestion for a Molecular Memory DeviceOrganized by DNA (Shown in Stereo)

Page 11: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Why DNA?Nucleic Acid Sequences Can Be Programmed and Synthesized, Leading to

Information-Based Structural, Dynamic and Catalytic ChemistryPredictable Intermolecular Interactions:Both Affinity and Structure.

Can Design Shape by Selecting Sequence:Robust Branched Motifs Programmable by Sequence.

Convenient Automated Chemistry:Both Vanilla DNA and Useful Derivatives.

Convenient Modifying Enzymes:Ligases, Exonucleases, Restriction Enzymes, Topoisomerases.

Locally A Stiff Polymer:Persistence Length ~500 Å; Stiff Branched Motifs Have Been Developed.

Robust Molecule:Can Heat Individual Strands without Doing Damage.

Amenable to Molecular Biology and Biotechnology Techniques:Gels, Autoradiography, PCR.

Externally Readable Code when Paired:Different Points in a Lattice Can be Addressed.

High Functional Group Density:Every 3.4 Å Nucleotide Separation.

Prototype for Many Derivatives:The Gene Therapy Enterprise Has Generated Hundreds of Analogs

Potentially Self-Replicable and Selectable:May be Able to Make and Improve Constructs Inexpensively.

DNA Topology Affects DNA Nanoconstructions

Chain Mail Interwoven

Page 12: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

What Is the Intellectual Goal ofStructural DNA Nanotechnology?

Controlling the Structure of Matter in 3D to theHighest Extent (Resolution) Possible, so as to

Understand the Connection betweenthe Molecular and Macroscopic Scales.

“What I cannot create, I do not understand.” --Richard P. Feynman

(Inverse not necessarily true.)

STRUCTURAL ANDTOPOLOGICAL

ASSEMBLIES

Page 13: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Polyhedral Catenanes

Cube: Junghuei Chen

Truncated Octahedron: Yuwen Zhang

Chen, J. & Seeman. N.C. (1991), Nature 350, 631-633..

Cube..

Page 14: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Zhang, Y. & Seeman, N.C. (1994),

J. Am. Chem. Soc. 116, 1661-1669.

TruncatedOctahedron

Page 15: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Constructionof

CrystallineArrays

REQUIREMENTS FOR LATTICEDESIGN COMPONENTS

PREDICTABLE INTERACTIONS

PREDICTABLE LOCAL PRODUCT STRUCTURES

STRUCTURAL INTEGRITY

Page 16: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Seeman, N.C. (2001) NanoLetters 1, 22-26.

Derivation of DX and TX Molecules

+

+

Resolve

Twice

2 Reciprocal

Exchanges

Resolve

Twice

2 Reciprocal

Exchanges

Resolve

Twice

2 Reciprocal

Exchanges

Resolve

Twice

2 Reciprocal

Exchanges

DS + DS DX TX

Strand

Polarity

Identical

Strand

Polarity

Opposite

Erik Winfree (Caltech)Furong Liu

Lisa Wenzler

2D DX Arrays

Page 17: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Schematic of a Lattice Containing1 DX Tile and 1 DX+J Tile

16 nm 16 nm

Winfree, E., Liu, F., Wenzler, L.A. & Seeman, N.C. (1998), Nature 394, 539-544.

AFM of a Lattice Containing1 DX Tile and 1 DX+J Tile

Page 18: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Schematic of a Lattice Containing 3 DX Tiles and 1 DX+J Tile

Winfree, E., Liu, F., Wenzler, L.A. & Seeman, N.C. (1998), Nature 394, 539-544.

AFM of a Lattice Containing3 DX Tiles and 1 DX+J Tile

Page 19: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Robust 2D Arrays:DX Triangles

Baoquan Ding

Simple Bulged 3-ArmJunction Triangle (1996)

J. Qi, X. Li, X. Yang & N.C. Seeman,

J. Am. Chem. Soc., 118, 6121-6130 (1996).

Page 20: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

DX Bulged Triangle Motif

Ding, B. & Seeman, N.C. (2004), J. Am. Chem. Soc. 126, 10230-10231.

Two Trigonal Motifs Form aPseudohexagonal Trigonal Array

Ding, B. & Seeman, N.C. (2004), J. Am. Chem. Soc. 126, 10230-10231.

Page 21: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Zoom

Lattice Views

Ding, B. & Seeman, N.C. (2004), J. Am. Chem. Soc. 126, 10230-10231.

Zoomed Images

Ding, B. & Seeman, N.C. (2004), J. Am. Chem. Soc. 126, 10230-10231.

Page 22: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

DIVERSIFYING THECHEMISTRY

Organizing 5 and 10 nmGold Nanoparticles

Jiwen ZhengPam Constantinou

Christine Micheel (Berkeley)Paul Alivisatos (Berkeley)

Rick Kiehl (Minnesota)

Page 23: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

The 3D-DX Triangle:A DX Version of the Tensegrity 3D Triangle

J. Zheng, P.E. Constantinou, C. Micheel, A.P. Alivisatos, R.A. Kiehl & N.C. Seeman, NanoLetters 6, 1502-1504 (2006).

YZ 2D Array of 3D-DX Triangle

One Tile Two Tiles

J. Zheng, P.E. Constantinou, C. Micheel, A.P. Alivisatos, R.A. Kiehl & N.C. Seeman, NanoLetters 6, 1502-1504 (2006).

Page 24: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Attachment of a Nanoparticle to the 3D-DX Motif

J. Zheng, P.E. Constantinou, C. Micheel, A.P. Alivisatos, R.A. Kiehl & N.C. Seeman, NanoLetters 6, 1502-1504 (2006).

Two Motifs Can Organize Nanoparticles

J. Zheng, P.E. Constantinou, C. Micheel, A.P. Alivisatos, R.A. Kiehl & N.C. Seeman, NanoLetters 6, 1502-1504 (2006).

Page 25: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Organized 5 nm and 10 nm Particles

J. Zheng, P.E. Constantinou, C. Micheel, A.P. Alivisatos, R.A. Kiehl & N.C. Seeman, NanoLetters 6, 1502-1504 (2006).

FROM GENES TOMACHINES:

DNA NANOMECHANICALDEVICES

Page 26: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

A Sequence-DependentDevice

Hao Yan

Derivation of PX DNA

Seeman, N.C. (2001) NanoLetters 1, 22-26.

+

+

DS + DS

Resolve

Everywhere

Reciprocal

Exchange

Everywhere

Resolve

Everywhere

Reciprocal

Exchange

Everywhere

PX

Strand

Polarity

Identical

Strand

Polarity

Opposite

Page 27: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

C D

PX

A B

JX2

A B

D C

Yan, H., Zhang, X., Shen, Z. & Seeman, N.C. (2002), Nature 415, 62-65..

Switchable Versions of PX and JX2

JX2

A B

D C

A B

C D

PX

SequenceDependent

Section

Page 28: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Machine Cycle of the PX-JX2 Device

A B

C D

A B

C D

A B

D C

JX2

A B

D C

PX

I II

IV III

System to Test the PX-JX2 Device

JX2

JX2

JX2

PXPXPX

Page 29: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

AFM Evidence for Operationof the PX-JX2 Device

Yan, H., Zhang, X., Shen, Z. & Seeman, N.C. (2002), Nature 415, 62-65.

A Robust 3-StateSequence-Dependent

Nanomechanical Device

Banani Chakraborty

Page 30: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

B. Chakraborty, R. Sha N.C. Seeman, (2008), Proc. Nat. Acad. Sci. (USA) 105, 17245-17249 (2008).

Three States of a Nanomechanical Device

Inserting a PX-JX2Device into a 2D Array

Baoquan Ding

Page 31: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Cassette To Be Inserted

B. Ding & N.C. Seeman, Science 314, 1583-1585 (2006).

Array for Insertion

B. Ding & N.C. Seeman, Science 314, 1583-1585 (2006).

Page 32: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Two States of the Array

B. Ding & N.C. Seeman, Science 314, 1583-1585 (2006).

Transitions in the Array

B. Ding & N.C. Seeman, Science 314, 1583-1585 (2006).

Page 33: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Transitions in the Array (Zoom)

B. Ding & N.C. Seeman, Science 314, 1583-1585 (2006).

Pairs of InsertedPX-JX2 Devices Usedto Program a Pattern

Hongzhou Gu

Page 34: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Programming an Array for Assembly

A. Carbone & N.C. Seeman, Proc. Nat. Acad. Sci. (USA) 99 12577-12582 (2002).

AFM Image of BlankOrigami Arrays for Insertion

H. Gu, J. Chao, S-J. Xiao & N.C. Seeman, Nature Nanotech., in press, (2009).

Page 35: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

AFM Image of Origami Arrayswith Inserted Cassettes

H. Gu, J. Chao, S-J. Xiao & N.C. Seeman, Nature Nanotech., in press, (2009).

Schematics of Programmed PatternsMade By Capturing Different Molecules

PX-PXPX-JX

JX-PXJX-JX

H. Gu, J. Chao, S-J. Xiao & N.C. Seeman, Nature Nanotech., in press, (2009).

Page 36: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

AFM Images of JX-JX Patterns

H. Gu, J. Chao, S-J. Xiao & N.C. Seeman, Nature Nanotech., in press, (2009).

AFM Images of JX-PX Patterns

H. Gu, J. Chao, S-J. Xiao & N.C. Seeman, Nature Nanotech., in press, (2009).

Page 37: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

AFM Images of PX-JX Patterns

H. Gu, J. Chao, S-J. Xiao & N.C. Seeman, Nature Nanotech., in press, (2009).

AFM Images of PX-PX Patterns

H. Gu, J. Chao, S-J. Xiao & N.C. Seeman, Nature Nanotech., in press, (2009).

Page 38: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

DNA Walking Biped

Bill Sherman

Schematic of the Device and Sidewalk

Sherman, W.B. & Seeman, N.C. (2004), NanoLett. 4, 1203-1207.

Page 39: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

The Steps in a Walk

Sherman, W.B. & Seeman, N.C.

(2004), NanoLett. 4, 1203-1207.

Animation of the Biped Walker

Courtesy of Ann Marie Cunningham and Donna Vaughn of ScienCentral News

Page 40: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

AutonomousDNA Walking Biped

Tosan Omabegho

Autonomous Walker Design

T. Omabegho, R. Sha, & N.C. Seeman, Science 324, 67-71 (2009).

Page 41: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Autonomous Walker Movement

T. Omabegho, R. Sha, & N.C. Seeman, Science 324, 67-71 (2009).

Autonomous WalkerUses Up the Track

T. Omabegho, R. Sha, & N.C. Seeman, Science 324, 67-71 (2009).

Page 42: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

Animation of theAutonomous Walker

T. Omabegho, R. Sha, & N.C. Seeman, Science 324, 67-71 (2009).

Summary of Results• Polyhedral Catenanes, Knots and Borromean Rings can be Assembled from Branched DNA by Ligation.

• 2D Lattices with Tunable Features have been Made from Branched DNA Components.

• 3D Crystals have been Self-Assembled and their Structures have been Determined.

• Heterologous Species have been Included in DNA Nanoconstructs.

• Nanomechanical Devices have been Assembled from Branched DNA, including a Translation Device a Clocked Walker, and an Autonomous Walker. A Machine has been Incorporated into a 2D Lattice and Used to Capture Pattern Components.

Page 43: Using DNA Information to Control the Structure of Matter in 3Ddnatec09/presentations/... · Reciprocal Exchange in a Double Helical Context Seeman, N.C. (2001), NanoLett. 1, 22-26

SUPPORTNational Institute of General Medical Sciences (1982-)

Office of Naval Research (1989-2004; 2009-)National Science Foundation (1997-)

DARPA/AFOSR (2001-2003)Army Research Office (2005-)

W. M. Keck Foundation (2006-)Nanoscience Technologies, Inc. (2003-2006)

Department of Energy -- NYNBIT (2006-2008)

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