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Nanoroadmap, Rome 2004 1
DNA-based molecular machines and devices
Friedrich C. Simmel
Department of Physics and Center for NanoscienceLudwig-Maximilians-Universität, Munich, Germany
simmel@lmu.de
Nanoroadmap, Rome 2004 2
1. Introduction: Bionanotechnology
2. DNA-based nanotechnology
3. DNA machines & devices
4. Outlook
Overview
Nanoroadmap, Rome 2004 3
1. Introduction: Bionanotechnology
2. DNA-based nanotechnology
3. DNA machines & devices
4. Outlook
Nanoroadmap, Rome 2004 4
Bionanotechnology
Nano → Bio:
using nanotechnologyfor life science applications
Nano → Bio:
using nanotechnologyfor life science applications
• lab on a chip
• lithographic techniques
• nanoparticles as biosensors or fluorescent markers
• nanocompartments for drug delivery
• lab on a chip
• lithographic techniques
• nanoparticles as biosensors or fluorescent markers
• nanocompartments for drug delivery
Examples:
Nanoroadmap, Rome 2004 5
Bionanotechnology
Nano → Bio:
using nanotechnologyfor life science applications
Nano → Bio:
using nanotechnologyfor life science applications
Expectations: • enhanced sensitivity (single molecules)
• integrated bioanalysis systems
• high-throughput screening
• coping with biological complexity (systems biology)
• enhanced sensitivity (single molecules)
• integrated bioanalysis systems
• high-throughput screening
• coping with biological complexity (systems biology)
Nanoroadmap, Rome 2004 6
Bionanotechnology
Bio → Nano:
using biotechnology for applications in nanoscience
Bio → Nano:
using biotechnology for applications in nanoscience
Examples: • biomolecular self-assembly
• molecular machines
• principles of biological self-organization
• reverse engineering of biological systems
• biomolecular self-assembly
• molecular machines
• principles of biological self-organization
• reverse engineering of biological systems
Nanoroadmap, Rome 2004 7
Bionanotechnology
Bio → Nano:
using biotechnology for applications in nanoscience
Bio → Nano:
using biotechnology for applications in nanoscience
• manufacturing by self-assembly
• molecular nanotechnology
• autonomous nanodevices
• synthetic biology
• manufacturing by self-assembly
• molecular nanotechnology
• autonomous nanodevices
• synthetic biology
Expectations:
Nanoroadmap, Rome 2004 8
1. Introduction: Bionanotechnology
2. DNA-based nanotechnology
3. DNA machines & devices
4. Outlook
Nanoroadmap, Rome 2004 10
A short introduction to DNA
base-pairing
complementary strands
form a double helix
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Useful: the biochemical toolbox for DNAUseful: the biochemical toolbox for DNA
• restriction enzymes:cut DNA at specific sequences
• ligases: link two DNA pieces covalently
• helicase: unwinds DNA
• topoisomerases: change topology (linking,winding number)
• DNA/RNA polymerases:make copies
• DNA binding proteins:help in recombination, function astranscriptional modulators, etc.
• restriction enzymes:cut DNA at specific sequences
• ligases: link two DNA pieces covalently
• helicase: unwinds DNA
• topoisomerases: change topology (linking,winding number)
• DNA/RNA polymerases:make copies
• DNA binding proteins:help in recombination, function astranscriptional modulators, etc.
http://www.bioteach.ubc.ca/MolecularBiology/RestrictionEndonucleases/endonuclease%202.gif
ligation of sticky ends
Nanoroadmap, Rome 2004 12
Important features of DNA for its utilization in nanoscience:Important features of DNA for its utilization in nanoscience:
• structure is determined by sequence(programmable self-assembly)
• automated DNA synthesis
• structurally rigid double helix with nanoscale dimensions
• DNA-modifying enzymes available
• PCR, cloning & other biochemistry
• relatively stable
• structure is determined by sequence(programmable self-assembly)
• automated DNA synthesis
• structurally rigid double helix with nanoscale dimensions
• DNA-modifying enzymes available
• PCR, cloning & other biochemistry
• relatively stable
Nanoroadmap, Rome 2004 13
• build nanostructures
• guide materials synthesis
• construct nanomechanical devices
• perform computations
• build nanostructures
• guide materials synthesis
• construct nanomechanical devices
• perform computations
DNA can be used toDNA can be used to
Nanoroadmap, Rome 2004 14
Chen et al.,Nature 350, 631-633 (1991) Zhang, Y. W. and N. C. Seeman (1994). JACS 116(5): 1661-1669.
Supramolecular DNA construction (a few examples)Supramolecular DNA construction (a few examples)
Yan, H., S. H. Park, et al. (2003).
Science 301(5641): 1882-1884.
Winfree et al., Nature ‘98
Liu, D.,et al. (2004).
JACS 126(8): 2324-2325Shih et al., Nature 427: 618-621 (2004)
Nanoroadmap, Rome 2004 15
DNA templating + scaffoldingDNA templating + scaffolding
Gartner, Z. J. and D. R. Liu JACS 123(28): 6961-6963.
Mirkin et al. Nature 382, 607 (1996),Alivisatos et al., Nature 382, 609 (1996),Coffer et al., APL 69, 3851-3853 (1996)
Xiao, S. J., F. R. Liu, et al. (2002) Journal of Nanoparticle Research 4(4): 313-317.
Dittmer & Simmel, APL 85, 633 (2004)Nickels et al., Nanotechnology 15, 1524 (2004)
Keren, K., et al. (2003). Science 302(5649): 1380-1382.
Beyer et al. (2004)Yan, H., et al. (2003). Science 301(5641): 1882-1884.
Nanoroadmap, Rome 2004 16
1. Introduction: Bionanotechnology
2. DNA-based nanotechnology
3. DNA machines & devices
4. Outlook
Nanoroadmap, Rome 2004 17
18 bp arm~ 6 nm
18 bp arm
4 nthinge 5 nm
48 ntloop
~ motorsection
A simple switch
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A three-state switchA three-state switch
Simmel & Yurke, PRE 63, 041913 (2001);Simmel & Yurke, APL 80, 883 (2002)
Nanoroadmap, Rome 2004 19
A three-state switchA three-state switch
Simmel & Yurke, PRE 63, 041913 (2001);Simmel & Yurke, APL 80, 883 (2002)
*
*
*strand displacementby branch migrationstrand displacementby branch migration
Nanoroadmap, Rome 2004 21
Examples for stretching and rotationExamples for stretching and rotation
Yan et al., Nature 415, 62 (2002)Li & Tan, NanoLetters 2, 315-318 (2002)
Yurke, Turberfield,Mills, Simmel & Neumann,Nature 406, 605 (2000)
Mao et al., Nature 397, 144-146 (1999)
Nanoroadmap, Rome 2004 22
Towards complex functional devicesTowards complex functional devices
• Locomotion
• Autonomy
• Function
• Control & Computing
• Locomotion
• Autonomy
• Function
• Control & Computing
Goals:Goals:
Nanoroadmap, Rome 2004 23
LocomotionLocomotion
A simpleDNA walkerwalks alonga track
A simpleDNA walkerwalks alonga track
Shin & Pierce, JACS 126, 10834 (2004)
Kinesin on Microtubule,Mandelkow lab
Nanoroadmap, Rome 2004 24
AutonomyAutonomyAn autonomous device based on a deoxyribozymeruns indefinitely until all fuel is consumed
An autonomous device based on a deoxyribozymeruns indefinitely until all fuel is consumed
Chen, Wang & Mao, Angew. Chem. Int. Ed., 43, 3554-3556 (2004)
Nanoroadmap, Rome 2004 25
FunctionFunction
An aptamer-based devicecan repeatedlygrab and release a protein
An aptamer-based devicecan repeatedlygrab and release a protein
Dittmer, Reuter & Simmel, Angew. Chem. Int. Ed. 43, 3550-3553 (2004)
Nanoroadmap, Rome 2004 26
ComputingComputing
A molecularcomputer decideswhether specificdisease indicatorsare present andadministers a drug
A molecularcomputer decideswhether specificdisease indicatorsare present andadministers a drug
Benenson et al.,Nature 429, 423 (2004)
Nanoroadmap, Rome 2004 27
Control by genetic mechanismsControl by genetic mechanisms
5’ ATG TAA TAC GAC TCA CTA TA GACC CGC ATA GAC CGT GAT TGT TAC CAG CGT TAG TTC AGA CAG TAG GAC TCC TGC TAC GA ATC CAT GAT ATC TGT TAG TTT TTT TCTAC ATT ATG CTG AGT GAT AT CTGG GCG TAT CTG GCA CTA ACA ATG GTC GCA ATC AAG TCT GTC ATC CTG AGG ACG ATG CT TAG GTA CTA TAG ACA ATC AAA AAA AG 5’
Dittmer, W. U. and F. C. Simmel (2004). Nano Letters 4(4): 689-691
transcriptional controltranscriptional control towards genetic controltowards genetic control
Nanoroadmap, Rome 2004 28
1. Introduction: Bionanotechnology
2. DNA-based nanotechnology
3. DNA nanodevices
4. Outlook
Nanoroadmap, Rome 2004 29
Integration into complex devicesIntegration into complex devices
Computation
ControlMotionFunction
Autonomy
autonomous devices which respond to external signals,make decisions and take action:
• move & transport • bind or release molecules• catalyze chemical reactions
Nanoroadmap, Rome 2004 30
this is useful forthis is useful for
nanotechnology:self-assembly & self-organizationof artificial nanocomponents
nanotechnology:self-assembly & self-organizationof artificial nanocomponents
biotechnology:intelligent molecular machines& devices for biosensors,diagnosis & drug delivery
biotechnology:intelligent molecular machines& devices for biosensors,diagnosis & drug delivery
Nanoroadmap, Rome 2004 31
Looking at biology with an engineering perspectiveLooking at biology with an engineering perspective
is it nano or is it bio ?
Nanoroadmap, Rome 2004 32
Stefan Beyer Wendy U. DittmerEike FriedrichsTim LiedlMichael OlapinskiAndreas Reuter
Patrick Nickels
Bernard Yurke (Bell Labs)Andrew Turberfield (Oxford U)Allen P. Mills jr. (UC Riverside)
Thank you !
Simon KellerJoachim O. RädlerJörg P. Kotthaus
€€: DFG, AvH, BMBF, Bayr. StMWFK, CeNS, ENNab
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