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Self-Organizing Bio-structures. NB2-2008 L. Duroux. Lecture 7. Protein-based nanomaterials. 1. Peptide-based nanostructures. A first insight into SA peptides. Concept of peptide SA introduced by Ghadiri et al. (1993)

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Self-Organizing Bio-structures

NB2-2008

L. Duroux


Lecture 7

Protein-based nanomaterials


1. Peptide-based nanostructures


A first insight into SA peptides

  • Concept of peptide SA introduced by Ghadiri et al. (1993)

  • Synthetic cyclic polypeptides (alternate L- & D-) self-assemble into Ø8-9nm nanotubes

  • Function as novel antimicrobial agents, drug delivery systems & nanomaterials


Ghadiri’s cyclic polypeptides (CPP)


Electronic microscopy


pH-dependance of CP SA


CPP forming pores in membranes


Self-Assembling Peptide Nanotubes

  • cyclic-peptides self-assembled into open tubes

  • consist of an even number of alternated D / L amino acids

  • formation of anti-parallel hydrogen bonded network

  • assembly could be controlled by electrostatic interactions

  • assembly could be directed toward particular environments (hydrophobic) by selection of amino acids

  • are functional material (ion channel & antibiotic)


SA based on native 2ndary structural motifs


Protein structural motifs & SA designs

Amyloid fibrils

Type II polyPro helix


SA Fibers engineering based on coiled-coils

Woolfson & Ryadnov, 2006


Amyloid peptides

  • A generic, universal form of protein/peptide aggregation

  • Cause of many diseases: Altzheimer’s, Type II diabetes, Prions...

  • Extended b-sheet SA forming fibrils


Nano-object formed by amyloid peptides

Object formed

Amyloid fibrils (pancreas type II diabetes)

Amyloid fibrils

Nanotubes

Nanospheres


The role of aromatics in amyloid fibrils formation

  • Phe dipeptide: the recognition core of Altzheimer’s amyloid fibril

  • Forms nanotubes

  • Applications in nano-electronics


SA based on amphiphilicity


Structures of peptides used in SA

Boloamphiphile

Amphiphile

Surfactant-like

Phenylalanine

dipeptide

Reches and Gazit, 2006


Peptide nanotubes

Applications

Nanotubes with Ca-binding and cell-adhesion  bone-like material

Idem, non-conjugated

Nanofibers forming hydrogel  matrix for tissue regeneration & engineering


Peptide-Amphiphile and Tissue Engineering

SA fibers with CCCCGGGS(PO4)PGD: without Ca2+ (a) and Ca2+ (b)


Aromatic dipeptides


Hydrophobic layers made with dipeptides

Görbitz, 2006


Types of nanostructures from various dipeptides


SA of Val-Ala class


SA patterns of the Phe-Phe class

Phe-Trp

Phe-Gly

Phe-Leu

Phe-Phe


Formation of nanotubes with Phe-Phe dipeptides


2. Protein-based SA nanotools


S-layer proteins


What are S-Layer proteins?

  • S stands for surface: glycoprotein subunits forming outer envelope of Bacteria and Archea

  • Periodic structures with defined physico-chemical properties (pore size)

  • Self_assemble into 2D layers to form monomolecular lattices: potential in nanobiotechnologies (scaffolds, patterning matrices)


Applications of S-layers

  • production of isoporous ultrafiltration membranes

  • supporting structures for defined immobilization or incorporation of functional molecules (e.g. antigens, antibodies, ligands, enzymes)

  • matrix for the development of biosensors including solid-phase immunoassays and label-free detection systems

  • Support and stabilizing matrices for functional lipid membranes, liposomes, and emulsomes

  • adjuvants for weakly immunogenic antigens and haptens

  • Matrix for controlled biomineralization and structure for formation of ordered arrays of metal clusters or nanoparticles (molecular electronics and nonlinear optics or catalysts)


S-Layer lattices

100nm

Gram+ bacterium


Self-Assembled monomolecular layers


S-layer as template for PSA detection


Assembly of lipids on S-layers

  • Non-covalent bonding

  • Electrostatic interactions between corrugated (inner) side of S-layer (carboxy groups) and charges on lipid head groups (zwitterions)

  • 2-3 contact points between protein and lipid: most lipids free to diffuse laterally: semi-rigid membrane


S-layers as support for lipid membranes


Self-Assembly of a ion-channel in S-layers


Expected applications of S-layer-driven SA of lipid membranes

  • Life Sciences:

    • Drug delivery

    • Diagnostics

    • Biosensors

  • Chemistry and material sciences

    • Bio-mineralization

    • Non-linear optics

    • Molecular electronics

    • Catalysis


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