Transcript Self-Organizing Bio

Self-Organizing
Bio-structures
NB2-2009
L. Duroux
Overall goal
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Give an insight of self-organizing processes in
nature and how these designs inspired humans
to create nano-sized objects
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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
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Jean-Marie LEHN (Nobel Chemistry, 1987)
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Chemistry beyond molecules  Supermolecules
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Organization, intermolecular non-covalent
bonds, different (better) properties than parts
Lecture Plan
1.
2.
3.
4.
5.
6.
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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
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Text Book: “The Emergence of life” by Pier L.
Luigi (ISBN: 0-521-82117-7)
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Text Book: “Supramolecular Chemistry –
Fundamentals and Applications, Advanced
Textbook” by Ariga and Kunitake (ISBN: 10 3-54001298-2)
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Selected review articles on specialized topics
Other Readings (specific topics)
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Self-Assembled Nanostructures, by J. Zhang et al, 2002, 340
p.,
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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
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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
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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
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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
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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
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Reducing conditions in deep-sea vents: Fe
chemistry, temperature >350degC:
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FeS + H2S  FeS2 + 2H+ + 2e-
Extreme thermophiles ribosomal RNA: most
primitive organisms known to date!
Prebiotic organics in early Earth
Exo-Biological sources
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Space dust: 40000 tons/year OR 8 ng/cm2
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Murchinson meteorite: 4.6 bY, amino acids,
purines, pyrimidines, carbox. Ac., polyols…
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Carbon as a result from H2 and He “burning”
(fusion) in stars
What was found or not in meteorites
or comets dust
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Found: diverse simple organic molecules,
membrane-forming aliphatic molecules
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Not found: polypeptides, mononucleotides
The question of “chemical selection”
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Why do Miller’s amino acids form (a-enantiomers)?
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a-amino-acids are more thermodynamically stable than bamino-acids
BUT: many molecules under kinetic controls  catalysts, i.e.
enzymes!
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Enzymes first? How possible?
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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
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Contingency
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A chemical pathway is determined by the cooccurrence of precursors in time and space
Determinism
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Nature has “chosen” a path that leads to further
developments/evolution (according to the laws n
Physics and Chemistry)
The Deterministic hypothesis
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Would a “wrong” thermodynamically stable
chemical lead to a dead-end in evolution OR to
an equally good alternative?
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Hypothesis tested by Eschenmoser et al. (1986):
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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
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Other “potentially natural” oses could give
alternative DNA with similar Tm
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Nature only selected D-ribose… a matter of
contingency or determinism?
On the origin of Molecular Asymmetry
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Why only one type of chirality in families of molecules
(L-form of amino-acids, D-form for sugars)?
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Why only one type of chirality and stereoregularity in
natural polymer chains?
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Any thermodynamic reason? Only subtle differences in
free energy between two forms (10-10 J).
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In chemistry, often racemic mixtures are obtained!
Molecular asymmetry
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See animation
Crystals as ”symmetry breakers”
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Achiral or racemic mixtures generally give
crystals with faces of opposite handedness: equal
probability to interface medium
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The face of the crystal at interface with medium
will induce racemisation of the solution (glycine
crystals)
Complementarity in homochirality
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Would life be possible with D-amino acids?
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Maybe, but only with L-sugars…
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Example: topoisomerase with D-amino-acids
incapable to recognise right-handed DNA!
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If enzymes catalyzed sugars synthesis…
In Summary
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Thermodynamic control: gives an initial set of favorable
products, essentially monomers
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Kinetic control: responsible for the diversification
(hence life), in particular polymers
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Sequence of 129aa of lysozyme not because most stable
combination!
Symmetry can be broken, but how does asymmetry
propagate?