Self-Organizing
Bio-structures
NB2-2009
L. Duroux
Overall goal

Give an insight of self-organizing processes in
nature and how these designs inspired humans
to create nano-sized objects

Lectures focuses on self-organization/selfassembly of bio-structures: molecules to supramolecular assemblies
SO & physics
Snowflake
Benard
Convection
Cells
Diffusion-limited
Aggregation
Sand Dune
SO & chemistry
micelle
keratin &
collagen
DNA
Simplex virus
SO & Biology
Slime mold
Daisy
Nautilus
Zebra
SO & Nanotechnology
Liquid
crystals
DNA tiles
Dendrimers
Bacteriorhodopsin
Supramolecular Chemistry

Jean-Marie LEHN (Nobel Chemistry, 1987)

Chemistry beyond molecules  Supermolecules

Organization, intermolecular non-covalent
bonds, different (better) properties than parts
Lecture Plan
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Pre-biotic chemistry (Ch. 2 & 3)
The formation of macromolecular sequences (Ch. 4)
Self-Organization in Biological systems (Ch. 5)
Supra-molecular Chemistry
Self-Assembly of Nucleic Acids
DNA in Nanotechnologies
Self-Assembly of Polypeptides
Proteins in Nanotechnologies
Viruses
Membranes
Supporting Material

Text Book: “The Emergence of life” by Pier L.
Luigi (ISBN: 0-521-82117-7)

Text Book: “Supramolecular Chemistry –
Fundamentals and Applications, Advanced
Textbook” by Ariga and Kunitake (ISBN: 10 3-54001298-2)

Selected review articles on specialized topics
Other Readings (specific topics)

Self-Assembled Nanostructures, by J. Zhang et al, 2002, 340
p.,

Hardcover ISBN: 978-0-306-47299-2
Self-Assembling Peptide Systems in Biology, Medicine and
Engineering, by A. Aggeli et al, 2001, 372 p., Hardcover
ISBN: 978-0-7923-7090-1

Self-Assembly in Supramolecular Systems, by L F Lindoy & I
M Atkinson, 2000, 234p., Hardcover ISBN 0 85404 512 0
Lecture 1
From Pre-Biotic Chemistry to
Macromolecular Assemblies
A scale of Molecular Complexity
towards Life







CELLS
METABOLIC NETWORKS
POLYMER COMPLEXES
MACROMOLECULES
BIOMONOMERS
MOLECULES
ATOMS
The origin of Life: a time scale
How did life emerge?
How can it be tested?
Formation of organic
molecules “building blocks”
Organic synthesis in reducing
atmosphere
The Urey-Miller Experiment (1953)
Synthesis of Adenine from cyanide
1.16Å
890kJ/mol
•Nitriles: highly polar group
(dipole: 3.9 Debye)
•Reaction: substitution (Ca),
addition on triple bond
•Condensation catalyzed by
heat (in aqueous medium)
Synthesis of Pyrimidine bases
CH4 + N2
spark
Synthesis of Aldoses
C=O
1.24Å
735kJ/mol


Aldehydes/ketones: permanent or induced dipole (O2
electronegativity)
Tautomery and H mobility on Ca  Nucleophilic
additions on Ca
Peptide bonds formation
Catalytic activity
Synthesis in nonreducing Atmosphere
The “Pyrite” hypothesis




In hydrothermal sources
Reduction of atm. CO2
and N2
Autotrophic  Final
product: pyruvate
Self-organized, coupled
chemical reactions:
metabolism from the
start!
Deep-sea vents biota

Reducing conditions in deep-sea vents: Fe
chemistry, temperature >350degC:


FeS + H2S  FeS2 + 2H+ + 2e-
Extreme thermophiles ribosomal RNA: most
primitive organisms known to date!
Prebiotic organics in early Earth
Exo-Biological sources

Space dust: 40000 tons/year OR 8 ng/cm2

Murchinson meteorite: 4.6 bY, amino acids,
purines, pyrimidines, carbox. Ac., polyols…

Carbon as a result from H2 and He “burning”
(fusion) in stars
What was found or not in meteorites
or comets dust

Found: diverse simple organic molecules,
membrane-forming aliphatic molecules

Not found: polypeptides, mononucleotides
The question of “chemical selection”

Why do Miller’s amino acids form (a-enantiomers)?


a-amino-acids are more thermodynamically stable than bamino-acids
BUT: many molecules under kinetic controls  catalysts, i.e.
enzymes!

Enzymes first? How possible?

How can selection (in Darwinian terms) be applied to
prebiotic chemistry?
The example of D-ribose in
RNA/DNA
Why
D-ribose
instead of
D-ribulose
?
Reasons for pre-biotic selection

Contingency


A chemical pathway is determined by the cooccurrence of precursors in time and space
Determinism

Nature has “chosen” a path that leads to further
developments/evolution (according to the laws n
Physics and Chemistry)
The Deterministic hypothesis

Would a “wrong” thermodynamically stable
chemical lead to a dead-end in evolution OR to
an equally good alternative?

Hypothesis tested by Eschenmoser et al. (1986):

D-furanose vs D-pyranose as the “sugar” for DNA
(homo-RNA)
Eschenmoser’s homo- and allo-DNA
Eschenmoser, 1999.
Science, 284:2118-2124
Stability of homo-DNA duplexes
Greater stability due to higher rigidity of pyranose ring: pre-oganisation
into helical structure
Other alternatives to D-ribose

Other “potentially natural” oses could give
alternative DNA with similar Tm

Nature only selected D-ribose… a matter of
contingency or determinism?
On the origin of Molecular Asymmetry

Why only one type of chirality in families of molecules
(L-form of amino-acids, D-form for sugars)?

Why only one type of chirality and stereoregularity in
natural polymer chains?

Any thermodynamic reason? Only subtle differences in
free energy between two forms (10-10 J).

In chemistry, often racemic mixtures are obtained!
Molecular asymmetry

See animation
Crystals as ”symmetry breakers”

Achiral or racemic mixtures generally give
crystals with faces of opposite handedness: equal
probability to interface medium

The face of the crystal at interface with medium
will induce racemisation of the solution (glycine
crystals)
Complementarity in homochirality

Would life be possible with D-amino acids?

Maybe, but only with L-sugars…

Example: topoisomerase with D-amino-acids
incapable to recognise right-handed DNA!

If enzymes catalyzed sugars synthesis…
In Summary

Thermodynamic control: gives an initial set of favorable
products, essentially monomers

Kinetic control: responsible for the diversification
(hence life), in particular polymers


Sequence of 129aa of lysozyme not because most stable
combination!
Symmetry can be broken, but how does asymmetry
propagate?