Self-Organizing Biostructures
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
ndary
2
structural motifs
Protein structural motifs & SA designs
Amyloid fibrils
Type II polyPro helix
SA Fibers engineering based on coiledcoils
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 PhePhe 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
1.
2.
3.
4.
5.
6.
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-layerdriven SA of lipid membranes

Life Sciences:




Drug delivery
Diagnostics
Biosensors
Chemistry and material sciences




Bio-mineralization
Non-linear optics
Molecular electronics
Catalysis