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Self Assembled Scaffolds &Self Assembled Scaffolds &
ApplicationsApplications
Natalie PazNatalie Paz
NanomedicineNanomedicineOctober 8, 2010October 8, 2010
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What is SelfWhat is Self-- Assembly?Assembly?
Defined as the spontaneous organizationDefined as the spontaneous organization
of individual components into an orderedof individual components into an ordered
structure with
outh
uman interventionstructure with
outh
uman intervention BottomBottom--upup
Stable structures mediated by weak,Stable structures mediated by weak,
noncovalent bonds:noncovalent bonds: hydrogen,waterhydrogen,water--mediatedmediatedhydrogen bonds, ionic bonds & hydrophobic & van derhydrogen bonds, ionic bonds & hydrophobic & van derWaals interactionsWaals interactions
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SelfSelf --Assembled ScaffoldsAssembled Scaffolds
Nucleic Acid Lattices & DNA ScaffoldsNucleic Acid Lattices & DNA Scaffolds
Peptide/Protein ScaffoldsPeptide/Protein Scaffolds
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DNA SelfDNA Self --AssemblyAssembly
Form SCAFFOLDS or templates forForm SCAFFOLDS or templates for
organizing and positioning other materialorganizing and positioning other material
nanoelectronic componentsnanoelectronic components
circuits (i.e RAM) & wirescircuits (i.e RAM) & wires
functional nanomechanical devicesfunctional nanomechanical devices
periodically patterned structuresperiodically patterned structures
molecular computing systemsmolecular computing systems
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DNA SelfDNA Self --AssemblyAssembly
Synthesis of SingleSynthesis of Single--stranded DNAstranded DNAmoleculesmolecules Branched Motifs (tiles)Branched Motifs (tiles) TilingTilinglatticeslatticeslarger nanolarger nano--meter scaledmeter scaled
structuresstructures SimpleSimple PeriodicPeriodicPatterningPatterning
Unmediated Algorithmic SelfUnmediated Algorithmic Self--AssemblyAssembly
Sequential StepSequential Step--Wise AssemblyWise Assembly Directed Nucleation AssemblyDirected Nucleation Assembly-- complexcomplexpatterned latticepatterned lattice
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DNA Self AssemblyDNA Self Assembly
ComplexComplex AperiodicAperiodicPatterningPatterning
Use Directed Nucleation Assembly with anUse Directed Nucleation Assembly with aninformationinformation--carrying inputcarrying input
DNA barcode lattice with aperiodic pattern wasDNA barcode lattice with aperiodic pattern wasformed (01101) by assembling double crossover (DX)formed (01101) by assembling double crossover (DX)DNA tiles around scaffold DNA strandsDNA tiles around scaffold DNA strands
DNA lattice with inverted pattern (10010) was fromedDNA lattice with inverted pattern (10010) was fromedby modifying and resynhesizing scaffold strand andby modifying and resynhesizing scaffold strand and
one strand composing each tileone strand composing each tile
Tiles can only assemble to form lattices inTiles can only assemble to form lattices inpresence of scaffold strandspresence of scaffold strands
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Lattice to ScaffoldLattice to Scaffold
Barcode latticeBarcode lattice(01101)(01101) a) antiparallel DX &a) antiparallel DX &
DX complex with
2DX complex with
2hairpin loopshairpin loops
b) five DX tilesb) five DX tilesassembled aroundassembled aroundinput scaffold DNAinput scaffold DNA
strand (3 DX+2J)strand (3 DX+2J) c)Schematicc)Schematic
d) (Atomic Forced) (Atomic ForceMicroscopy of latticeMicroscopy of lattice
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Lattice to ScaffoldLattice to Scaffold
Inverted patternInverted pattern
lattice (10010)lattice (10010)
Same concept asSame concept as
previous slideprevious slide Except, modifiedExcept, modified
scaffold strand (2scaffold strand (2
DX+2J)DX+2J)
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Lattice to ScaffoldLattice to Scaffold
Figure 1:Figure 1:
i.e. (011101i.e. (011101--1011010110--01101).01101).May align in opposite orMay align in opposite orsame orientationsame orientation
BluntBlunt--endsends Naturally align with oneNaturally align with one
another to protect theirhelixanother to protect theirhelixends from exposure to water.ends from exposure to water.
Helix stacking interactionsHelix stacking interactionsare vital in DNA lattice selfare vital in DNA lattice self--
assemblyassemblyFigure 2:Figure 2:
Add complementary stickyAdd complementary sticky--ends to form long ribbonsends to form long ribbons
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Peptide/Protein ScaffoldsPeptide/Protein Scaffolds
Versatile building blocksVersatile building blocks
for fabricating materialfor fabricating material
Scaffolds for naturalScaffolds for natural
material (collagen,material (collagen,keratin, pearl, shell, coral)keratin, pearl, shell, coral)
Scaffolds for tissue repairScaffolds for tissue repair
in regenerative medicine,in regenerative medicine,
drug delivery & biologicaldrug delivery & biological
surface engineeringsurface engineering
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Types of Peptide MaterialsTypes of Peptide Materials
Fabrication of nanofibersFabrication of nanofibers Ionic self complementary peptidesIonic self complementary peptides
~5nm in size~5nm in size
Form BForm B--sheet structures in aqueous solutions with two distinct surfacesheet structures in aqueous solutions with two distinct surface hydrophilic andhydrophilic andhydrophobichydrophobic
Form complementrary ionic bonds with regular repeats on the hydrophilic surfaceForm complementrary ionic bonds with regular repeats on the hydrophilic surface
((--++--++--,, ----++)++) Ordered self assemblyOrdered self assembly
Interwoven matrices to form scaffold hydrogelInterwoven matrices to form scaffold hydrogel
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Types of Peptide MaterialsTypes of Peptide Materials
Surface nonSurface non--coating peptidecoating peptide
Three distinct segments: ligand (i.e RGD),Three distinct segments: ligand (i.e RGD),
linker and anchorlinker and anchor
Ink for inkjet printer to print arbitrary patternsInk for inkjet printer to print arbitrary patterns
directly on surfacedirectly on surface
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Types of Peptide MaterialsTypes of Peptide Materials
Molecular Switch peptideMolecular Switch peptide Strong dipoles undergo conformational changesStrong dipoles undergo conformational changes
under external stimuli btw alphaunder external stimuli btw alpha--helix & Beta strandhelix & Beta strandor Beta sheetor Beta sheet
Metal nanocrystals could attach to fabricate tinyMetal nanocrystals could attach to fabricate tinyswitchesswitches
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Protein Fibrous ScaffoldsProtein Fibrous Scaffolds
3D Scaffolds3D Scaffolds Interwoven nanofibers withInterwoven nanofibers with
diameter of ~10nm & poresdiameter of ~10nm & poresof ~5of ~5--200nm in size200nm in size
Exposing selfExposing self--assemblingassemblingpeptide to a salt solution orpeptide to a salt solution orto a physiological mediato a physiological media
Greater tendency to formGreater tendency to formpeptide matrices if alaninespeptide matrices if alaninesare replaced with moreare replaced with more
hydrophobic residueshydrophobic residues(valin, leucine or tyrosine)(valin, leucine or tyrosine)
Used for cell cultures & cellUsed for cell cultures & cellgrowth studiesgrowth studies
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ReferencesReferences
Shuguang Zhang, David M Marini, Wonmuk Hwang, Steve Santoso. DesignShuguang Zhang, David M Marini, Wonmuk Hwang, Steve Santoso. Designof nanostructured biological materials through selfof nanostructured biological materials through self--assembly of peptidesassembly of peptidesand proteins. Current Opinion in Chemical Biology 2002, 6:865and proteins. Current Opinion in Chemical Biology 2002, 6:865--871871
Shuguang Zhang. Fabrication of novel biomaterials through molecular selfShuguang Zhang. Fabrication of novel biomaterials through molecular self--assembly. Nanotechnology 2003, 21:1171assembly. Nanotechnology 2003, 21:1171--11781178
Debanti Sengupta, Sarah C. Heilshorn. ProteinDebanti Sengupta, Sarah C. Heilshorn. Protein--Engineered Biomaterials:Engineered Biomaterials:
Highly Tunable Tissue engineering Scaffolds. Tissue Engineering 2010,Highly Tunable Tissue engineering Scaffolds. Tissue Engineering 2010,16:28516:285--291291
Hao Yan, Thomas H. LaBean, Liping Feng, John H. Reif. DirectedHao Yan, Thomas H. LaBean, Liping Feng, John H. Reif. Directednucleation assembly of DNA tile Complexes for barcodenucleation assembly of DNA tile Complexes for barcode--patterned lattices.patterned lattices.PNAS 2003, 100:8103PNAS 2003, 100:8103--81088108
Sung Ha Park, Hao Yan, John H Reif, Thomas H LaBean, Gleb Finkelstein,Sung Ha Park, Hao Yan, John H Reif, Thomas H LaBean, Gleb Finkelstein,Nanotechnology 2004, 15:525Nanotechnology 2004, 15:525--527527
Hidenori Yokol, Takatoshi Kinoshita, Shuguang Zhang. Dnamic reassemblyHidenori Yokol, Takatoshi Kinoshita, Shuguang Zhang. Dnamic reassemblyof peptide RADA16 nanofiber scaffold. PNAS 2004, 102:8414of peptide RADA16 nanofiber scaffold. PNAS 2004, 102:8414--84198419
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