1. Self-Assembly
Ho-Lin Chen
Nov

2. Self-Assembly
Self-Assembly is the process by which simple objects autonomously assemble into complexes.
Geometry, dynamics, combinatorics are all important
Inorganic: Crystals, supramolecules
Organic: Proteins, DNA, cells, organisms
Goals: Understand self-assembly, design self-assembling systems
A key problem in nano-technology, molecular robotics, molecular computation

3. Applications of Self-Assembly
Building blocks of nano-machines.
DNA computing.
Small electrical devices such as FLASH memory. [Black et. Al. ’03]
Nanostructures which “steer” light in the same way computer chips steer electrons. [Percec et. Al. ’03]

4. Self-Assembly of DNA
[Winfree]

5. Abstract System Model

6. DNA Tiles Glues = sticky ends Tiles = molecules G4 G3 = G1 G2
[Fu and Seeman, ’93]
Glues = sticky ends
Tiles = molecules

7. abstract Tile Assembly Model:
[Rothemund, Winfree, ’2000]
Temperature: A positive integer. (Usually 1 or 2)
A set of tile types: Each tile is an oriented rectangle with glues on its corners. Each glue has a non-negative strength (0, 1 or 2).
An initial assembly (seed).
A tile can attach to an assembly
iff the combined strength of the
“matched glues” is greater or
equal than the temperature. x z x y

8. Example: Sierpinski System
[Winfree, ’96] 1 1 1 1
T=2 1 1 1 1 1

9. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 1

10. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 1 1

11. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 1 1

12. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 1 1 1 1

13. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1

14. DAO-E Sierpinski triangle experiments
Paul Rothemund, Nick Papadakis, Erik Winfree, PLoS Biology 2: e424 (2004)
340nm

15. Theoretical Results
Efficiently assembling basic shapes with precisely controlled size and pattern.
Constructing N X N squares with O(log n/log log n) tiles. [Adleman, Cheng, Goel, Huang, ’01]
Perform universal computation by simulating BCA.
[Winfree ’99]
Assemble arbitrary shape by O( Kolmogorov complexity) tiles with scaling. [Soloveichik, Winfree ’04]

16. Block Cellular Automata
f(X, Y) g(X, Y)
X Y

17. Simulating BCA T=2 A series of tiles with format: Growth direction
f(X,Y)
g(X,Y)
A series of tiles with format: X Y
Growth direction
seed

18. Assemble Arbitrary Shapes
Replace each tile by a block.
Size of block = O(computation time)
computation

19. Tile System Design
Library of primitives to use in designing nano-scale structures
[Adleman, Cheng, Goel, Huang, ’01]
Automate the design process
[Adleman, Cheng, Goel, Huang, Kempe, Moisset de espanes, Rothemund ’01]

20. Kinetic System Model

21. kinetic Tile Assembly Model:
[Winfree, 1998]
A tile can attach
at any location.
The rate of attachment
rf = constant.
The rate of detachment rr,b = c e-bG

22. Kinetic model => Abstract model
We set the temperature and concentration to
rr,T+1 << rr,T < rf << rr,T-1
If a tile attaches with strength < T-1, it is likely to fall off very fast.
If a tile is held by strength at least T+1, it is unlikely to fall off

23. Error Correction

24. Robustness Designs Use biological mechanisms in the process.
Add extra structure/modification on the process of DNA self-assembly.
Add combinatorial structures to tile systems.
Use the original erroneous process, but add more structure to the tile system to do error correction.

25. Using Biological Mechanisms
Use strand invasion
[Chen, Cheng, Goel, Huang, Moisset de espanes, ’04]
Add protecting tiles
[Fujibayashi and Murata, ’04]

26. Strand Invasion

27. Strand Invasion

28. Strand Invasion

29. Strand Invasion

30. Strand Invasion

31. Strand Invasion

32. Strand Invasion

33. Strand Invasion

34. Strand Invasion

35. Strand Invasion

36. Strand Invasion

37. Strand Invasion

38. Strand Invasion

39. Strand Invasion

40. Strand Invasion

41. Strand Invasion

42. Strand Invasion

43. Strand Invasion

44. Strand Invasion

45. Strand Invasion

46. Strand Invasion (cont)

47. Strand Invasion

48. Strand Invasion

49. Example
T=2

50. Example
T=2

51. Example
T=2

52. What can go wrong?
T=2

53. What can go wrong?
T=2

54. Why it may not matter:
T=2

55. Why it may not matter:
T=2

56. What can go really wrong?

57. What can go really wrong?

58. What can go really wrong?

59. Safe attachments and invadable systems
Unsafe
Definition: A tile system is an invadable system iff for all assemblies that can be grown from the initial assembly, all possible attachments are safe.

60. Using Combinatorial Systems
Proofreading tiles
[Winfree and Bekbolatov, ’02]
Snaked tiles
[Chen and Goel, ’04]
Self healing tiles
[Erik Winfree, ’05]

61. Nucleation Error (T=2)
Starting from an initial assembly

62. Nucleation Error (T=2) The first tile attaches with strength 1.
(usually falls off fast)

63. Nucleation Error (T=2) The second tile attaches and now both
tiles are held by strength 2.

64. Nucleation Error (T=2)
Error propagates.

65. Modelling Errors Temperature: A positive integer. (Usually 1 or 2)
A set of tile types: Each tile is an oriented rectangle with glues on its corners. Each glue has a non-negative strength (0, 1 or 2).
An initial assembly (seed).
Rules: A tile can attach to an assembly iff the combined strength of the “matched glues” is greater or equal than the temperature.
Tiles with combined strength equal to temperature can fall off.
Errors: Once a while, there will be two tiles attach at the same time and both are held by strength at least two after the attachment.
We call this an “insufficient attachment”.
Our goal: minimize the impact of insufficient attachments

66. Snaked Tile System [Chen, Goel, 2004] Replace a tile by
G1b X4 X3
G2a X2
G3b
G2b
G1a
G4a
G4b
G3a
Blunt end (inert)
Replace a tile by
a block of 4 tiles
Internal glues are unique

67. Nucleation Error (T=2)
Starting from an initial assembly

68. Nucleation Error (T=2) Two tiles attach and both tiles
are held by strength 2.

69. Nucleation Error (T=2)
No other tiles can attach.
Inert edge

70. Generalization G1 G4 G3 G2

71. Theoretical Analysis
The snake tile design can be extended to 2k by 2k blocks.
Prevents tile propagation even after k-1 insufficient attachments happen.

72. Why it works? bad ............ : insufficient attachments
: erroneous tiles falling off

73. Why it works? bad ............ : happens with rate O(e-G) * rf
: erroneous tiles falling off

74. Theoretical Analysis
The snake tile design can be extended to 2k by 2k blocks.
Prevents tile propagation even after k-1 insufficient attachments happen.
When < k insufficient attachments happened locally, all the erroneous tiles are expected to fall off in time poly(k).

75. Why it works? bad ............ : happens with rate O(e-G) * rf
: happens with rate 1/poly(k)

76. Why it works? bad ............ bad : happens with rate O(e-kG)
if backward rate >> forward rate

77. Theoretical Analysis
If we want to assemble a structure with size N, we can use Snaked Tile System with block size k=O(log N).
The assembly process is expected to finish within time Õ(N) and be error free with high probability.

78. Experimental Verification
Joint work with
Ashish Goel
Rebecca Schulman
Erik Winfree

79. Snaked Tile System [Chen, Goel, 2004] Replace a tile by
G3b
G4b G1 G2
G3a X3 X2
G4a
Replace a tile by
a block of 4 tiles
Internal glues are unique
G1b X4
Blunt end
G2b
G1a
G2a

80. 1 3 1c 3c 2c 4c 2 4 2 4 1c 2c 1 2 4 4c 2 4

81. Tile sets used in experiments
Proofreading block
Snaked block 4 3 4 3 1 1 2 2 3c 3c 4c 4c 1c 2c 1c 2c

82. [Schulman, Winfree, DNA 10, 2004]
Width-4 Zig-Zag Ribbon
[Schulman, Winfree, DNA 10, 2004]
6 tile types

83. AFM of Zig-Zag Ribbons

84. ZZ + Snake Tiles 10 tile types Side A Side B (no glue) 1 3 1c 3c 2c 4c

85. Slow nucleation and growth!
ZZ + Snake Tiles 1 3 1c 3c 2c 4c 2 4 1 3 1c 3c 2c 4c 2 4
Side A 2 1 3 1c 3c 2c 4c 2 4 4 2 4 2 4
Side B
(no glue)
10 tile types

86. Fast nucleation and growth!
ZZf + Snake Tiles 2 4 2c 4c 1c 3c 1 3 2 4 3c 3
Side A 4c 1 1 2 4 2c 4c 1c 3c 1 3 3 2c 1c 1 3 1 3
Side B
(no glue)
10 tile types

87. Zig-Zag ribbons used in experiments
name
description
Normal Zig-Zag
(ZZ)
Side A: Glues 2, 4
Side B: blunt
Flipped
(ZZf)
Side A: Glues 1, 3
Double_sided
(ZZ_DS)
Side B: Glues 1, 3
Flipped + double_sided
(ZZ_DSf)
Side B: Glues 2, 4
slow
fast
slow
fast
fast
slow
snake tiles

88. Experiment Results

89. ZZf nM Snaked block

90. Zig-Zag + 100 nM Snaked block

91. Zig-Zag + 100 nM Proofreading

92. ZZf nM Proofreading

93. ZZ_DS + 10 nM Proofreading

94. ZZ_DS + 10 nM Snaked block

95. Ratio of chunks on each side
Statistics
Ratio of chunks on each side
Zig-Zag
Side A: glues 2, 4
Side B: glues 1, 3
Side A: glues 1, 3
Side B: glues 2, 4
Snaked block
4.7
4.2
Proofreading block
1.1
1.5

96. Ratio of tiles on each side
Statistics
Ratio of tiles on each side
Zig-Zag
Side A: glues 2, 4
Side B: glues 1, 3
Side A: glues 1, 3
Side B: glues 2, 4
Snaked block
4.3
3.9
Proofreading block
1.0
1.2

97. Self-healing Tile System
[Winfree, ’ 05]
Goal: When a big portion of the lattice is removed, it should be able to grow back correctly.
Method: For each tile in the original system, we create a unique block in the new system.
Idea: Use the block to prevent tile from growing backwards.

98. Assumption Use abstract tile assembly model.
Requires a fix set of incoming and outgoing edges for each tile in the original system.

99. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 1

100. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 1

101. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1

102. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1
destroyed

103. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 1 1

104. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1

105. Example: Sierpinski System1 1 1 1
T=2 1 1 1 1 ? ?

106. Example (T=2) Replace a tile by a block of 4 tilesG3 G4 G1 G2 G3 X4 X2 G4
Replace a tile by
a block of 4 tiles
Internal glues are unique X1 X3 G1 G2

107. Poly-amino safe
The system is save even when several tiles can form a bigger block before attach to the assembly.

108. Example (T=2) Replace a tile by a block of 4 tilesG3 G4 G1 G2 G3 X4 X2 G4
Replace a tile by
a block of 4 tiles
Internal glues are unique X1 X3 G1 G2

109. Poly-amino safe
The system is save even when several tiles can form a bigger block before attach to the assembly. X1 X3 G1 G2

110. Poly-amino safe
The system is save even when several tiles can form a bigger block before attach to the assembly. G3 X4 X1 X3 G1 G2

111. Poly-amino safe
The system is save even when several tiles can form a bigger block before attach to the assembly. G3 X4 X2 G4 X1 X3 G1 G2

112. Poly-amino safe
The system is save even when several tiles can form a bigger block before attach to the assembly. G3 X4 X2 G4 X1 X3 G1 G2

113. Poly-amino Safe
The system is save even when several tiles can form a bigger block before attach to the assembly. G3 X4 X2 G4 X1 X3
Attach to assembly G1 G2

114. Not Poly-amino Safe Replace a tile by a block of 4 tilesG3 G4 G1 G2 G3 X4 X2 G4
Replace a tile by
a block of 4 tiles
Internal glues are unique X1 X3 G1 G2

115. Self-Healing System Use blocks of size 7. Poly-amino safe.
Arbitrary growth directions.

116. Future Work Optimum tile system design
Theories apply to general self-assembly systems
Some other error correction designs
More experimental verification

117. Thanks!