PazNatalie Leading Discussion

8/8/2019 PazNatalie Leading Discussion

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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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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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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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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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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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