Jianpeng Ma Baylor College of Medicine and Rice University, - - PowerPoint PPT Presentation

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Jianpeng Ma Baylor College of Medicine and Rice University, - - PowerPoint PPT Presentation

Tuesday, March 18, 11:40am Auditorium - French Family Science Center, Room 2231 Jianpeng Ma Baylor College of Medicine and Rice University, Department of Bioengineering Simulating, Refining and Modeling Supramolecular Complexes at


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Tuesday, March 18, 11:40am Auditorium - French Family Science Center, Room 2231

Jianpeng Ma

Baylor College of Medicine and Rice University, Department of Bioengineering

Simulating, Refining and Modeling Supramolecular Complexes at Multi-resolution and Multi-length Scales

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Bionanotech - proteins

 Engineering  Design  Catalysis  Self-assemblies  Templates & scaffolds  Surface coatings  Sensors

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Tuan Vo-Dinh, Fitzpatrick Institute for Photonics

 Nanostructures and self-

assemblies

 Drug delivery  Biosensors  Molecularly imprinted

polymers

Humana Press

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Protein Nanotech

 Engineered assemblies  Organization of nanomaterials  Biosensors  Biomineralization

Biological Species Example Typical size MW (daltons) Small protein Chymotrypsin 4 nm sphere 104-105 Large protein Asp.transcarb. 7 nm sphere 105-107 Small assembly Ribosome 20 nm sphere 105-107 Large assembly Viruses 100 nm sphere 107-1012 Nucleic acids tRNA 10 nm rod 104-105

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Protein Design

 De novo design vs. library selection

 Felix, Beta-bellin (Richardsons)  α4 (DeGrado)  TOP7 (David Baker)  Computational Function Design (Hellinga)  Sequenomics (Schultes, LaBean)

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Protein arrays

streptavidin streptavidin biotin biotin

L-rhamnulose-1-phosphate aldolase

7x7x5 nm 6x5x4 nm

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Protein arrays

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Protein arrays

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Protein arrays

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Protein arrays

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Protein arrays

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Bionanotech - proteins

 Engineering  Design  Catalysis  Self-assemblies  Templates & scaffolds  Surface coatings  Sensors

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Chaperonin arrays

 Chaperonins

 Natural function: protein folding assistants or actually

misfolding “inhibitor”.

 Heat-shock protein.  Multimer assembles given ATP & Mg++; large internal

cavity.

 15 - 20 nm assemblies.

 Sulfolobus shibatae

 Lives in geothermal hot-springs (85°C, pH 2).  Theromstable protein easy to purify and engineer.  Sequence & structure available for modeling.  Assembles into higher order structures (2D crystals).

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Chaperonin arrays

HSP60 beta

3 nm pore 9 nm pore

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Chaperonin arrays

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Chaperonin arrays

XEDS

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S-layer arrays

 Crystalline bacterial cell

surface layers.

 ~5x105 monomers/cell  Biosynth ~500 copies/sec

 Purified S-layer proteins

self-assemble into arrays.

 Pores and functional

groups available for engineering.

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S-layer arrays

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S-layer arrays

p4 p6 p4

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S-layer arrays

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S-layer arrays

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S-layer arrays

 Diversity of:

 Geometry  Pore size  pI  Glycosylation sites  Etc.

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S-layer arrays

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S-layer arrays

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S-layer arrays

UV S-layer mask

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Bionanotech - proteins

 Engineering  Design  Catalysis  Self-assemblies  Templates & scaffolds  Surface coatings  Sensors

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Self-assembling peptide templates

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Self-assembling peptide templates

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Metal nanowires from peptide templates

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Metal nanowires from peptide templates

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Metal nanowires from peptide templates

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Metal nanowires from peptide templates

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Metal nanowires from peptide templates

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Bionanotech - proteins

 Self-assemblies  Templates & scaffolds

 Nanoparticles  Metals  Silica, minerals, ceramics,

semiconductor

 Surface coatings

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Site-Specific Biological Delivery Systems Daniel Kenan

AFFINERGY

www.affinergy.com Most Materials are “Biohostile”

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Objective:

Attach a specific biological material (cell, antibody, protein, etc.) to... A synthetic material (plastics, metals, glass, etc.)

 Use a small linker to tie

the two peptides together

 Identify peptide that binds to

synthetic material w/ high affinity

Interfacial Biomaterials (IFBM)

 Identify peptide that binds to

biological material w/ high affinity and selectivity IFBM Coating

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IFBMs Configured as Cell Attractants Polystyrene Binding Peptide Synthesized with RGD

FFPSSWYSHLGVLSSGRGD

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Titanium orthopedic screw with Stem Cells

IFBM Attachment of preadipocytes IFBM Blocking

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IFBM’s Mediate Rapid & Efficient Cell Adhesion on Ti

  • IFBM, 10’

+ IFBM, 10’

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Mineralization of IFBM-Supported Stem Cells at 45d

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  • Titanium
  • Stainless Steel
  • Teflon
  • PET, PETG, PGA
  • Polystyrene
  • Polycarbonate
  • Glass, Nylon, Latex
  • Growth Factors
  • Cell Receptors
  • Cell Matrix Proteins
  • Collagen
  • Enzymes
  • Antibodies

IFBM Discovery Platform: > 4 billion peptides in libraries 3 to 6 month cycle to find binders Binders found for every target tried Biases can be built into selection Range of affinities and specificities can be exploited

IFBM Platform

Drugs Peptides Proteins Cells

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Stainless Steel ePTFE DES Chrome Cobalt Nitinol Collagen Synthetic Scaffolds Resorbables Damaged Heart Tissue Cells Tie 2 Modulators Ang1 Ang2 Growth Factors Cell Receptors tPA New Targets

Rapid Solutions Due to Modularity of Affinergy’s Platform

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Bionanotech - proteins

 Engineering & design

 Custom catalysts

 Self-assemblies

 Nano organizers

 Templates & scaffolds  Surface coatings

 Nanoimprint or DPN inks  Tissue regeneration

 Sensors

 Sensitivity & selectivity

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Molecularly Imprinted Polymers

 “Artificial proteins”  Mimic protein functions

 Molecular recognition (binding)  Catalysis

 Higher stability  Manufacture greater quantities

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Molecularly Imprinted Polymers

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Molecularly Imprinted Polymers