Algorithmic self-assembly for nano-scale

fabrication

Erik Winfree Computer Science

Computation & Neural Systemsand

The DNA Group @ Caltech

DARPA NSF NASA

Constructing Complex Molecular Objects(Development/Morphogenesis)

Information specifies a process that creates organization

Creating OrderBlueprints,Template

-------------Arbitrary structure.

Larger object requires

larger template.

Periodiccrystals

-------------Few components,

large homogeneousobject.

Algorithmicgrowth

-------------Few components,

large intelligently-organized

object.

Nadrian Seeman &

DNA nanotechnology

Chemical structure of DNA

G

A

A

G

T

C

C

T

DNA

single-stranded double-stranded

AGTCTTCGAATGCTAATTGCGCT

AGCGCAATTAGCATTCGAAGACT

Designing DNA molecular complexes

Nadrian Seeman, 1980’s

GATTACA

CTAATGTTAGGCAG

ATCCGTC

AC

TG

GT

G

TG

AC

CA

C

GATTACA

CTAATGT

ATCCGTC

TG

AC

CA

C

AC

TG

GT

G

TAGGCAG

Chen and Seeman, Nature 350, 631 (1991).

Periodic 2-tile crystal (DAO-E lattice)

TCACT

AGTGA

CATAC

GTATG

TCTTG

AGAAC ATCTC

TAGAG

Winfree, Liu, Wenzler, Seeman, Nature 394: 539-544 (1998)

1 24 3

3 42 1

Self-Assembly of DNA

High resolution AFM imaging

Hole = lattice defect Conformation of helix and sticky ends?

Rizal Hariadi, Winfree groupcrystal growth movie

Some variations

Mao, Sun, Seeman, JACS 1999

Winfree, Liu, Wenzler, Seeman, Nature, 1998

LaBean et al, JACS, 2000

More variations

1D ribbons

1D tubes

(Schulman, Winfree, 06)

Zigzag ribbon 2D periodic

lattices

Nano-track

3-helix bundle

TX-tube

6-helix bundle

4x4 tube

DX tube

DX lattice

TX lattice

4x4 lattices

triangle lattice

hexagonal lattice

3 point-star lattices

symmetry lattice

single-strand DX-like tubes …

Rhombus ribbon

…

(Mao, Sun & Seeman, 1999)

Rhombus lattice

(Mao, Sun & Seeman 99)

(Winfree, Liu, Wenzler & Seeman 98)

(LaBean, Yan, Kopatsch, Liu, Winfree, Reif, & Seeman 00)

(Liu, Park, Reif & LaBean 04)

(Liu, Wang, Deng, Walulu & Mao 04) (He, Tian, Chen, Deng,

Ribbe & Mao 05)

(He, Chen, Liu,Ribbe & Mao 05)

(He, Chen, Liu,Ribbe & Mao 05)

(Park, Yin, Liu, Reif LaBean & Yan 05)

(Park, Barish, Li, Reif,Finkelstein,Yan & LaBean 05)

(Rothemund, Ekani-Nkodo, Papadakis, Kumar,

Fygenson & Winfree 04)

… (Mathieu, Liao,

Kopatsch, Wang, Mao & Seeman

05)

Chiral DX tube

(Mitchell, Harris, Malo, Bath &Turberfield 04)

HJ lattice

(Malo, Mitchell, Venien-Bryan, Harris,Wille,Sherratt &

Turberfield 05)

(Reishus, Shaw, Brun,Chelyapov & Adleman 05)

DDX lattice

(Chelyapov, Brun, Gopalkrishnan, Reishus, Shaw & Adleman 04)

(Yan, Park, Finkelstein,Reif & LaBean 03)

(Yan, Park, Finkelstein,Reif & LaBean 03)

TX ribbon

(Li, Park, Reif, LaBean, Yan 03)

(Rothemund 05)

SAO lattice

DNA computing

Adleman, Science (1994)

Len Adleman:DNA self-assembly is programmable

The Sierpinski Triangle(aka Pascal’s Triangle mod 2)

0 0 0 0 0 0 0 1 0 0 0 0 0 0 00 0 0 0 0 0 1 1 0 0 0 0 0 0

0 0 0 0 0 0 1 0 1 0 0 0 0 00 0 0 0 0 1 1 1 1 0 0 0 0 0

0 0 0 0 0 1 0 0 0 1 0 0 0 00 0 0 0 1 1 0 0 1 1 0 0 0 0

0 0 0 0 1 0 1 0 1 0 1 0 0 0

0 0 0 0 0 0 1 1 0 0 0 0 0 0

each new number is the sum of the two below it

Paul Rothemund, Nick Papadakis, Erik Winfree, PLoS Biology 2:e424, 2004

The Sierpinski Triangle(aka Pascal’s Triangle mod 2)

Paul Rothemund, Nick Papadakis, Erik Winfree, PLoS Biology 2:e424, 2004

The Sierpinski Triangle

(aka Pascal’s Triangle mod 2)

Paul Rothemund, Nick Papadakis, Erik Winfree, PLoS Biology 2:e424, 2004

DAO-E Sierpinski Tile Set

decorrelation movie powers of two movie

Making the boundary (the input string)

750

nm

}

25 nm

DAO-E Sierpinski experiments

Algorithmic crystals

1.6 um scan

deco

rrel

atio

n m

ovie

scaffold strand

algorithmic growth

errors during assembly

DAO-E Sierpinski triangle experiments

Paul Rothemund, Nick Papadakis, Erik Winfree, PLoS Biology 2: e424 (2004)

340nm

Scaffolded DNA origami

Folding long single-stranded DNA

The sequence of DNA provides unique addresses for each location.

“Staple strands” bind locations together according to the design.

Folding long single-stranded DNA

The sequence of DNA provides unique addresses for each location.

“Staple strands” bind locations together according to the design.

Folding long single-stranded DNA

The sequence of DNA provides unique addresses for each location.

“Staple strands” bind locations together according to the design.

Scaffolded DNA origami

Scaffolded DNA origami

Scaffolded DNA origami

Creating OrderBlueprints,Template

-------------Arbitrary structure.

Larger object requires

larger template.

Periodiccrystals

-------------Few components,

large homogeneousobject.

Algorithmicgrowth

-------------Few components,

large intelligently-organized

object.