Complex Materials & BioNanoTechnology
Prof. Jürgen Fritz
International University Bremen
Summer school on "Complex Materials: Cooperative Projects of the Natural Sciences, Engineering and Biosciences"
IUB, June 2006
Scope & Motivation
Complex Materialsnew materials with components on the micro- / nanometer scale with integrated functionand assembled by bottom up approach
BioNanotechnologyuse of natural components (biomolecules) for novel non-biological applicationsone dimension on nanometer scale influencing functionality
Outline general ideas on bio for physics, nano & interdisciplinarityenvironment for nano (surfaces and fluidics)systems (DNA, peptides, proteins)
(overview of the field related to our research but not on our research)
2 µm Kaw
ata,
Nat
ure
2001
bottom up top down
system size10 µm
cartilage cell micro-sculptured bull
J. Fritz, IUB 2006
blood cellsE. coli bacteriaflagella rotorantibody
quantum corral carbon nanotubemagnetic bitsintegrated circuits
DNA
separate, detect, quantify, analysestructure, function, organization
light/electron microscopy, X-rays,spectroscopy, ultracentrifuge,
MS, NMR, electrophoresis,patch clamp, …
single molecule methods,arrays, microfluidics,biosensors, system biology,simulations, …
toolsuniversal laws
self-assembly,molecular recognition, autonomy, molecular machines & electronics,efficiency, complexity …
concepts,designs
new approach to computation & ITenergy storage & conversion, actuation
Biology
Physics
biophysics &
nanotechnology
transistor
J. Fritz, IUB 2006
Physical versus biological systems
physical device
highly defined, reliable, reproduciblerobust & durablesimple materials, periodicsuperior electronic propertiestop down fabricationserial assembly of single componentshigh energy costs
biological system
individual, dependent on environmentflexible & short lifetimecomplex materials, aperiodicrecognition and self-assembly capabilitybottom up assembly parallel assembly of multiple componentslow energy costsintrinsic information processingself-replicating
J. Fritz, IUB 2006
"A Physicist looks at biology"
Other missconceptions by using biosystems
- evolution does not choose the best option, just the best available option- biosystems are selected for their function, but not every feature of a biological system
has a functional importance- there is no ideal or model biological system as in physics or engineering- error correction needed for bottom up approach & self-assembling
Max Delbrück (Nobelprize 1969, in: The Connecticut Academy of Arts and Sciences, 1949)
" There are no absolute phenomena in biology. Everything is time bound and space bound."
" The materials and phenomena (a physicists) works with are the same here and nowas they were at all times and as they are on the most distant stars. "
Biomolecules are normally not optimized for applications in engineering
J. Fritz, IUB 2006
Complex MaterialsBioNanotechnology
Physicsmechanics, electrodynamics,quantum mechanics, solid state physics,mesoscopic physics
Chemistrysynthesis, catalysiscolloids, nanotubes
Biologymolecular recognition,evolution, self-assembly,molecular machines
Modelling& Simulation
Engineeringelectronics, computing,microfabrication
Surface Sciencescanning probe methods, self assembled monolayers
devicesapplications
materialsapplications
complexityautonomy
toolslaws
Medicinediagnostics,health care
problemsapplications
J. Fritz, IUB 2006
Nanotechnology - small is different
mechanics & chemistry- surface properties gain importance (reactivity, surface to volume ratio)- increasing resonance frequencies- position affected by thermal noise, random motion and uncertainty principle
electromagnetic properties- interaction with light (diffraction, scattering, imaging and lithography)- electronic structure (density of state and term schemata)- magnetic structure (domain size, spin flip)
transport- transport properties: charges - diffusion, ballistic, hopping, tunneling
fluidics - turbulent vs. laminar- thermal relaxation time decreases
interaction forces- electromagnetic & van der Waals forces dominate (vs. gravity)
general description- ensemble properties vs. distribution of individual properties (statistics)
J. Fritz, IUB 2006
Driving BioNanotechnology
Scientific challenge & new insightsinterdisciplinarity, converging length scales in physics, chemistry and biology ...
Miniaturization in medicine, advances in pharmaceutical industryscreening, delivery, lab-on-a-chip, implantable devices,...
Future of electronics (information technology)Moores Law, shrinking devices, higher integration, ...
Chemical industry & engineeringcompound selection, intelligent materials,
improved performance, ...
source: Intel
J. Fritz, IUB 2006
Good to know for BioNanotechnology
Systemsbiomolecules, macromolecules, interactions, cells, ...>> objects of interest for modification, novel applications
Environmentsurfaces (surface chemistry, physics, ... )fluidics (microfluidics)>> positioning, delivery, manipulation of nanosystems
TechniquesSPM (STM, AFM, ...)fluorescence (FRET, FCS, ...)conductance measurements (ion channels, molecular wires, ...)modelling and simulation (molecular mechanics, molecular dynamics, ...) >> information on single molecules and nanoscale properties
Not covered here (chemical or optical systems):nanoparticles (metal, semiconducting, ...) nanotubespolymers, dendrimerssupramolecular chemistry....
Zhang, Science 2004
Kat
z &
Will
ner,
Che
mP
hysC
hem
200
4
J. Fritz, IUB 2006
Surfaces for NanoBiotechnology
General ideas
- bind nanosystem to surfaces todefine its position for precise analysis and manipulationsidentify system by selective binding
- use surfaces as support & templates for 2D structures
- position molecules in nanocontainers for well-defined reactions or transport
surfacesmicrofluidicsDNApeptidesproteins
" Surfaces and interfaces define the boundary of an object and its interactionswith other systems and they define the chemical environment of nanosystems "
J. Fritz, IUB 2006
Surface properties
Uni
vers
ity o
f B
asel
Typical surfacessilicon oxide (glass), gold, metal oxides, ...carbon, polymers, lipid membranes, ...
General surface propertiesroughness, flexibility, charge, hydrophobic/-philic, ...adhesive, repellent, ...
Surface functionalitiespermeability, reactivity, changing properties by functionalization, active switching, ...
J. Fritz, IUB 2006
Active control of surfaces
Example- reversible light-induced photoisomerization changes surface free energy- gradient in surface tension induces driving force for liquids on flat surfaces
írradiation with UV light> cis-azo groups
> increase in surface free energy> spread of drop
Ichimura, Science 2000
Other switching mechanism: electrowetting
" control surface properties to control fluids and objects "
Catalytic properties of surfaces
~ 400 nm
~ 2 µm
Pt catalyzes decomposition of hydrogen peroxide> oxygen gradient along rod
> interfacial tension along rod decreases with increase of oxygen> movement in direction of Pt
speed about ~ 10 body length per second (as bacterial flagellae)
rod trajectories
Paxton, JACS 2004
50 µm
Catchmark, Small 2005
" tailor reactivity of surface to control motion of nanoobjects "
Surfaces and nanocontainers
Phospholipids
liposomes as nanoreactorsinsert membrane channelsstabilize liposomes with polymers
lipid bilayer as functional membranes for nanocontainers
" design closed surfaces to protect or transport sample "
J. Fritz, IUB 2006
text
book
Nanotube - vesicle networks
forced shape transformation by micromechanicaltools: carbon fiber or pipette suction
1 - 50 µm vesicles, tubes 25 - 300 nm diameter
Karlsson, Annu Rev Phys Chem 2004Tokarz, PNAS 2005
" container networks by partitioning surfaces "
electrophoresis within nanotubes
Liquid environment for BioNanotechnology
surfacesmicrofluidicsDNApeptidesproteins
Aqueous solutionnatural environment for biological systems (buffer: pH, ions)buffer composition determines molecular conformation and interaction
of molecules and objects:- ionic distribution around charged objects / surfaces- ordering of water molecules (hydration forces, hydrophobicity)- end-to-end distance of polymers, swelling of gels, ...
Governing interactionsBrownian motion and diffusionviscous and inertial forces (turbulent or laminar flow)surface tension (capillary forces)
Small, well defined volumesshorter reaction times, less samplehigh concentrations with small number of moleculesdefined delivery of molecules or nanoobjects
" the two best defined experimental environments are UHV & low temperaturesor a pure & well defined solution (at fixed potential) "
25 nm
1 H+
pH 7.4 → pH 4J. Fritz, IUB 2006
Laminar flow
Reynolds number:
(velocity, length scale, density, viscosity)
Properties of laminar flow (small Re < 1000)viscous forces (friction) dominateno turbulenceno mixing except by diffusionreversible liquid motionliquid packets can be moved in a controlled way
Beebe, Annu Rev Biomed Eng 2002
ηρdv
FFRe
frict
inert ⋅⋅==
Gu, PNAS 2004
" motion in liquids is governed by inertial and frictional forces "
ship in water: inertial forces dominate, ship keeps movingeven when propulsion is stopped
bacteria in water: viscous (frictional forces) dominatewithout propulsion bacteria stops immediately
Quake group, Science 2000 & 2002
Large scale integration of microfluidics
air pressured valves out of PDMS
controlled motion of liquid packets
1 2
3 4
thousands of valves, hundreds of reaction chambers
Non-biological applications of DNA
surfacesmicrofluidicsDNApeptidesproteins
Why DNA ?- robust molecule, well defined structure- can be easily synthesized & modified- model system for molecular recognition and self-assembly- reversible hybridization - denaturation
hybridization
designed(probe)
sample(target)
ssDNA dsDNA
J. Fritz, IUB 2006
Conduction through DNA ?
since 1961: stack of base pairs along helix axis, with overlapping π system postulated: semiconducting with 1.5 - 3 eV gap
BUTconduction strongly depends on length, sequence, environment, structure, contact to electrodes...
unistep tunneling sequential hopping molecular band conduction
Porath, Nature 2000
DNA as a wire ?
600 nm long molecule ohmic
Fink, Nature 1999 Porath, Nature 2000
10 nm longsemiconducting
contradicting results from electronic measurements
Storm, Appl. Phys. Lett. 2001
40 - 500 nm longinsulating
DNA as template for electronics
aggregation of silver around DNA wirediameter ~ 100 nm
Braun et al., Nature 1998
Niemeyer, ChemBioChem 2001
assembly of biotinylated DNAand streptavidin
thiolated DNA and gold beads
Seeman, Nature 2003
Artificial DNA superstructures" use self-assembly of DNA to get microscopic 2D structures "
Holliday Junctions can form during meiosis
Design DNA sequences to interweave different strands
Micrometer sized DNA sheets
Winfree et al., Nature 1998
self-assembly of a mixture ofdifferent designed sequences(colors) in solutionscale bars 300 nm, 1 - 2 nm height
stripes:extruding hairpins
Design of arbitrary 2D DNA structures
Rothemund, Nature 2006scale bars 100 nm
one long strand of viral ssDNA (~ 7000 nt) as scaffoldthen design different short complementary strands
3D structures ?
Seem
an
Remote control of DNA
RF On = denaturated Off = hybridized
RF (1 GHz) magnetic radiation (~ mT, 0.4 to 4 W)
Hamad-Schifferli, Nature 2002
1.4 nm gold nanocrystal38mer oligonucleotide
UV absorption (hyperchromicity)
heat∆T + 13 C
ssDNA
dsDNA
Molecular Machines
MIT Media Laboratory
no beads
" bind / unbind DNA at will by external trigger "
control
Peptides for organic - inorganic interactions
surfacesmicrofluidicsDNApeptidesproteins
Why peptides ?more building blocks (20 amino acids) with more interactions (than DNA)- charged, polar, hydrophobic, aromatic
more structures possible
BUT: more sensitive than DNA, harder to analyze and synthesize
peptides:some ten amino acids
J. Fritz, IUB 2006
Self-assembly
- molecules form spontaneously ordered aggregates without external intervention- non-covalent interacting mobile components, reversible
Whitesides, Science & PNAS 2002
Natural peptide assemblies
Vendruscolo, Phil Trans R Soc Lond A 2003
Amyloid fibrilsresponsible for diseases like Alzheimer or type II diabetis10 nm diameter, beta-sheet rich structure
misfolding, e.g. lysozyme Goldsbury, JMB 1999
100 nm
growth of amylin (37 aa peptide hormone)
protein assembly: actin filaments, microtubules, bacterial S-layer, ...
Self-assembly of artificial peptides
Zhao, Trends Biotech 2004
peptide lego with alternating pos. and neg. residues and hydrophobic backsidepeptide surfactants with hydrophobic tails and hydrophilic headspeptides for self-assembling on surfaces, pattern surfaces
Peptides shape crystal growth
- crystals grown by marine organism differ dramatically from grown in solution- calcite (calcium carbonate) growth
pure calcite calcite + Mg2+ calcite + D-aspartic acid calcite + AP8 protein(from abalone nacre)
DeYoreo, Science 2004
Natural assembly of inorganic materialsMagnetosomesmagnetic nanoparticles inmagnetotactic bacteria
BäuerleinAngew Chem Int Ed 2003
Diatomssingle celled algae with sculptured wallsof amorphous silica
Drum, Trends Biotech 2003
Abalone shellsrigid (hard but brittle) by calcium carbonatetough (energy absorbant but flexible) by proteins
Addadi, Nature 1997, Rubner, Nature 2003
50 µm, 1 µm
100 nm
GaAs
SiO2
Surface recognizing peptides
evolutionary selection of 12mer peptides with surface recognition propertiespage display with M13 bacteriophage with peptide fused to coat protein
Belcher group, MIT
selective for:material, crystalline faces, identical lattice of different materialGaAs(100), GaAs(111), InP(100), Si (100)
many uncharged polargroups
Whaley, Nature 2000
" peptides can be evolved to recognize any (?) solid state surface "
ZnS-A7 phage film
Proteins - complex nanomachines
surfacesmicrofluidicsDNApeptidesproteins
lipid bilyer
water
water
aquaporin(water channel)~ 10 9 molecules /secexcludes H+ and ions
Why proteins?highly complex systems: enzymes, channels, motors, receptors, ...inspiring, the ultimate complex molecular system
BUT: not optimized for foreign environmements, difficult preparation and analysis(100 - 10.000 aa)
de Groot, Science 2001
J. Fritz, IUB 2006
Vale, Science 2000
Molecular motors
myosin on actin kinesin on microtubules
muscle contractionstepping motion5 nm step size8000 nm / sec
intracellular transportprocessive motion8 nm step size840 nm / sec
powered by ATP
Molecular shuttles by motor proteins
Hess, Rev Mol Biotech 2001
kinesin at surface, 1 mM ATPrhodamin labeled microtubules 1 - 10 µmcarefully triggered environment (pH, T, salt,...)
" molecular motors in artificial environment "
Molecular rotors
time
revo
lutio
ns
Yasuda, Cell 1998
Flow of protons across membrane (F0) is used to synthesizeATP (F1) and ATP hydrolysis can pump protons in reverse direction
F0 and F1 coupled by shaft which rotatesF1 ATPase activity > counter clockwise, stepwise rotation of 120 °around 1 rotation / sec
Forced ATP synthesis
Itoh, Nature 2004
" artificial synthesis of ATP by mechanical rotation "
magnetic bead attached to shaft of F1 ATPase, rotated shaft by magnets clockwisedetecting ATP synthesis by enzymatic reaction (fluorescence)5 min intervalls: N - no rotation, H - in hydrolysis direction, S - in synthesis directionca. 105 ATP per 5 min
Conclusions
- glimps of BioNanoTechnology & non-biological applications of biomolecules- overview of workshop topics- learning from nature on molecular scale: components for complex materials- interdisciplinarity:
important to understand concepts, language and thinking of your colleagues
Jürgen Fritz: Complex Materials & BioNanoTechnology
NanoBioTechnology at IUB
Prof. J. Fritz: AFM, biosensors, microfluidicsProf. M. Winterhalter: lipids, liposomes, membrane channelsProf. U. Schwaneberg: biochemical engineeringProf. M. Zacharias: biomolecular modelingProf. V. Wagner: organic field-effect transistors, molecular electronicsProf. S. Tautz: low temperature STM, small molecules on metalsProf. U. Kortz: synthetic chemistry, metal-oxygen clusters Prof. W. Nau: photochemistry, biomolecular dynamicsProf. R. Richards: nanoparticles, catalysis...
Tautz
Kortz
Schwaneberg
J. Fritz, IUB 2006
Some General References
IntroductionK. Satoshi et al.: Finer features for functional microdevices, Nature412 (2001) 697.M. Delbrück: A physicist looks at biology, Trans. Connecticut Acad. Arts Sciences 38 (1949) 173.
SurfacesK. Ichimura et al.: Light-driven motion of liquids on a photo-responsive surface, Science 288 (2000) 1624.W.F. Paxton et al.: Catalytic nanomotors: Autonomous movement of striped nanorods, JACS 126 (2004) 13424.M. Karlsson et al, Biomimetic nanoscale reactors and networks, Annu. Rev. Phys. Chem. 55 (2004) 613.
FlowD.J. Beebe et al.: Physics and applications of microfluidics in biology, Annu. Rev. Biomed. Eng. 4 (2002) 261.T. Thorsen et al.: Microfluidic large-scale integration, Science 298 (2002) 582.
DNAC. Dekker et al.: Electronic properties of DNA, Phys. World 14 (2001) 29.C.M. Niemeyer: Nanoparticles, proteins, and nucleic acids: Biotechnology meets materials science, Angew. Chem. Int. Ed. 40 (2001) 4128.N.C. Seeman: DNA in a material world, Nature 421 (2003) 427.P.W.K. Rothemund: Folding DNA to create nanoscale shapes and patterns, Nature 440 (2006) 297.K. Hamad-Schifferli et al.: Remote electronic control of DNA hybridization through inductive coupling to an attached metal nanocrystal antenna, Nature 413 (2002) 152.
PeptidesG.M. Whitesides et al.: Beyond molecules: Self-assembly of mesoscopic and macroscopic components, PNAS 99 (2002) 4769.X. Zhao et al.: Fabrication of molecular materials using peptide construction motifs, Trends Biotech. 22 (2004) 470.J.J. DeYoreo et al.: Shaping crystals with biomolecules, Science 306 (2004) 1301.R.W. Drum et al.: StarTrek replicators and diatom nanotechnology, Trends Biotech. 21 (2003) 325.N.C. Seeman et al.: Emulating biology: Building nanostructures from the bottom up, PNAS 99 (2002) 6451.
ProteinsR.D. Vale et al.: The way things move: Looking under the hood of molecular motor proteins, Science 288 (2000) 88.R. Yasuda et al.: F1-ATPase is a highly efficient molecular motor that rotates with discrete 120° steps, Cell 93 (1998) 1117.H. Itoh et al.: Mechanically driven ATP synthesis by F1-ATPase, Nature 427 (2004) 465.
J. Fritz, IUB 2006
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