DNA: Not Merely the Secret of Life

Bio-Inspired Bottom-Up Nanoscale Control of the Structure of Matter

Nadrian C. Seeman

Department of ChemistryNew York University

New York, NY 10003, USAned.seeman@nyu.edu

Workshop on the ComputationalWorld View and the Sciences

Princeton UniversityDecember 11, 2006

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

CC

NC

C

N

NC

OC

H

NR

H

N H

H

G

3.4 Å

~20 Å

10-10.5Pairs/Turn

B-DNA

Reciprocal Exchange:A Theoretical Tool To Generate

New DNA Motifs

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

R e cip roc a lE x ch an ge

R e s o lve

Reciprocal Exchange in aDouble Helical Context

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

+

+S t r a n d

P o l a r i t y

I d e n t i c a l

S t r a n d

P o l a r i t y

O p p o s i te R e s o l v e

R e c i p r o c a l

E x c h a n g e

R e s o l v e

R e c i p r o c a l

E x c h a n g e

D S + D S H J

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

Design of Immobile Branched Junctions:Minimize Sequence Symmetry

IIACTCGTGCTGAGCACG••••••••

A

T

C

G AT A

T AT

C

G

C

G C

G• • • • • • • •

3322

11 44

C GC G

CGA TA T

ATCG

C G

••••••••

IV

I

III

C GCG

C GA TA T

ATC G

•••••••

C G•

Sticky-Ended Cohesion: Smart Affinity

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

Sticky-Ended Cohesion: Structure

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

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

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

A Method for Organizing Nano-Electronic Components

Why DNA?Predictable 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.