DNA: Not Merely the Secret of Life
Bio-Inspired Bottom-Up Nanoscale Control of the
Structure of Matter
Nadrian C. Seeman
Department of Chemistry
New York University
New York, NY 10003, USA
ned.seeman@nyu.edu
Workshop on the Computational
World View and the Sciences
Princeton University
December 11, 2006
B-DNA
D N A BASE PAIRS
A
T
H
3.4 Å
H
C
N
N
C
N
3
C
C
C
C
CH
O
H
N
H
C
N
H
R
N
C
C
H
N
R
O
G
C
H
H
C
C
N
H
O
N
C
C
C
N
H
H
~20 Å
C
C
C
N
H
C
N
R
N
H
N
O
N
R
H
Reciprocal Exchange:
A Theoretical Tool To Generate
New DNA Motifs
Reciprocal
Exchange
Resolve
Seeman, N.C. (2001), NanoLett. 1, 22-26.
Reciprocal Exchange in a
Double Helical Context
DS + DS
HJ
Reciprocal
Exchange
Strand
Polarity
Identical
+
Resolve
Reciprocal
Exchange
Strand
Polarity
Opposite
+
Resolve
Seeman, N.C. (2001), NanoLett. 1, 22-26.
Design of Immobile Branched Junctions:
Minimize Sequence Symmetry
I
C • G
G • C
C • G
A • T
A • T
T • A
1
C • G
4
C • G
II
G C A
• • •
C G T
T G A T A C C G
• • • • • • • •
A C T A T G G C
C G A G T
• • • • •
G C T C A
IV
C • G
2
C• G
3
G• C
A • T
A • T
T • A
G • C
C • G
III
Seeman, N.C. (1982), J. Theor.Biol. 99, 237-247.
Sticky-Ended Cohesion: Smart Affinity
Sticky-Ended Cohesion: Structure
Qiu, H., Dewan, J.C. & Seeman, N.C. (1997) J. Mol. Biol. 267, 881-898.
The Central Concept of Structural DNA Nanotechnology:
Combine Branched DNA with Sticky Ends to
Make Objects, Lattices and Devices
B'
B'
A
B'
A'
A
A'
B
A
A'
B
B
Seeman, N.C. (1982), J. Theor.Biol. 99, 237-247.
OBJECTIVES AND APPLICATIONS
FOR OUR LABORATORY
ARCHITECTURAL CONTROL AND SCAFFOLDING
[1]
[2]
[3]
[4]
MACROMOLECULAR CRYSTALLIZATION (PERIODIC IN 2D AND 3D).
NANOELECTRONICS ORGANIZATION (PERIODIC IN 2D AND 3D).
DNA-BASED COMPUTATION (APERIODIC IN 2D OR 3D).
CONTROL OF POLYMER AND MATERIALS COMPOSITION & TOPOLOGY.
NANOMECHANICAL DEVICES
[1] NANOROBOTICS.
[2] NANOFABRICATION.
CURRENT CRYSTALLIZATION PROTOCOL
GUESS CONDITIONS
SET UP CRYSTALS
DO CRYSTALLOGRAPHY
PRAY FOR CRYSTALS
CRYSTALS?
YES
NO
CHANGE DEITIES
GUESS NEW CONDITIONS
A New Suggestion for Producing Macromolecular Crystals
Seeman, N.C. (1982), J. Theor.Biol. 99, 237-247.
A Method for Organizing Nano-Electronic Components
Robinson, B.H. & Seeman, N.C. (1987), Protein Eng. 1, 295-300..
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.