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

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1. Introduction: Bionanotechnology

2. DNA-based nanotechnology

3. DNA machines & devices

4. Outlook

Overview

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1. Introduction: Bionanotechnology

2. DNA-based nanotechnology

3. DNA machines & devices

4. Outlook

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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:

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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)

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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

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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:

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1. Introduction: Bionanotechnology

2. DNA-based nanotechnology

3. DNA machines & devices

4. Outlook

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A short introduction to DNA

DNA/RNA bases

single-stranded DNA

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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

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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

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• 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

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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)

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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.

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1. Introduction: Bionanotechnology

2. DNA-based nanotechnology

3. DNA machines & devices

4. Outlook

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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)

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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

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Operation of a three-state switchOperation of a three-state switch

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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)

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Towards complex functional devicesTowards complex functional devices

• Locomotion

• Autonomy

• Function

• Control & Computing

• Locomotion

• Autonomy

• Function

• Control & Computing

Goals:Goals:

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LocomotionLocomotion

A simpleDNA walkerwalks alonga track

A simpleDNA walkerwalks alonga track

Shin & Pierce, JACS 126, 10834 (2004)

Kinesin on Microtubule,Mandelkow lab

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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)

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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)

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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)

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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

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1. Introduction: Bionanotechnology

2. DNA-based nanotechnology

3. DNA nanodevices

4. Outlook

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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

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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

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Looking at biology with an engineering perspectiveLooking at biology with an engineering perspective

is it nano or is it bio ?

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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