Self-Self-Organizing Organizing

Bio-Bio-structuresstructuresNB2-2009NB2-2009

L. DurouxL. Duroux

Overall goalOverall goal

Give an insight of self-organizing Give an insight of self-organizing processes in nature and how these processes in nature and how these designs inspired humans to create designs inspired humans to create nano-sized objectsnano-sized objects

Lectures focuses on self-Lectures focuses on self-organization/self-assembly of bio-organization/self-assembly of bio-structures: molecules to supra-structures: molecules to supra-molecular assembliesmolecular assemblies

SO & physicsSO & physics

SnowflakeDiffusion-limitedAggregation

Benard Convection Cells

Sand Dune

SO & chemistrySO & chemistry

micelle DNA

Simplex viruskeratin & collagen

SO & BiologySO & Biology

Slime mold Nautilus

Daisy Zebra

SO & NanotechnologySO & Nanotechnology

Liquid crystals

Dendrimers

DNA tiles Bacterio-rhodopsin

Supramolecular Supramolecular ChemistryChemistry

Jean-Marie LEHN (Nobel Chemistry, Jean-Marie LEHN (Nobel Chemistry, 1987)1987)

Chemistry beyond molecules Chemistry beyond molecules SupermoleculesSupermolecules

Organization, intermolecular non-Organization, intermolecular non-covalent bonds, different (better) covalent bonds, different (better) properties than partsproperties than parts

Lecture PlanLecture Plan

1.1. Pre-biotic chemistry (Ch. 2 & 3)Pre-biotic chemistry (Ch. 2 & 3)2.2. The formation of macromolecular The formation of macromolecular

sequences (Ch. 4)sequences (Ch. 4)3.3. Self-Organization in Biological systems (Ch. Self-Organization in Biological systems (Ch.

5)5)4.4. Supra-molecular ChemistrySupra-molecular Chemistry5.5. Self-Assembly of Nucleic AcidsSelf-Assembly of Nucleic Acids6.6. DNA in NanotechnologiesDNA in Nanotechnologies7.7. Self-Assembly of PolypeptidesSelf-Assembly of Polypeptides8.8. Proteins in NanotechnologiesProteins in Nanotechnologies9.9. VirusesViruses10.10. MembranesMembranes

Supporting MaterialSupporting Material

Text Book: “The Emergence of life” by Text Book: “The Emergence of life” by Pier L. Luigi Pier L. Luigi (ISBN: 0-521-82117-7)(ISBN: 0-521-82117-7)

Text Book: “Text Book: “Supramolecular Chemistry –Fundamentals and Applications, Advanced Textbook” by Ariga and Kunitake (ISBN: 10 3-540-01298-2)

Selected review articles on specialized Selected review articles on specialized topicstopics

Other Readings (specific Other Readings (specific topics)topics)

Self-Assembled Nanostructures, Self-Assembled Nanostructures, by J. Zhang by J. Zhang

et alet al,, 20022002, 340 p.,, 340 p., Hardcover ISBN: 978-0-306-47299-2Hardcover ISBN: 978-0-306-47299-2

Self-Assembling Peptide Systems in Biology, Self-Assembling Peptide Systems in Biology, Medicine and Engineering, Medicine and Engineering, by A. Aggeli et al, by A. Aggeli et al, 20012001, 372 p., , 372 p., HardcoverHardcoverISBN: 978-0-7923-7090-1ISBN: 978-0-7923-7090-1

Self-Assembly in Supramolecular SystemsSelf-Assembly in Supramolecular Systems, , by L F Lindoy & I M Atkinson, by L F Lindoy & I M Atkinson, 20002000, 234p., , 234p., Hardcover Hardcover ISBNISBN 0 85404 512 0 0 85404 512 0

Lecture 1Lecture 1

From Pre-Biotic Chemistry to From Pre-Biotic Chemistry to Macromolecular AssembliesMacromolecular Assemblies

A scale of Molecular Complexity towards Life

CELLS METABOLIC NETWORKS POLYMER COMPLEXES MACROMOLECULES BIOMONOMERS MOLECULES ATOMS

The origin of Life: a time The origin of Life: a time scalescale

How did life emerge?How did life emerge?How can it be tested?How can it be tested?

Formation of organic Formation of organic molecules “building molecules “building

blocks”blocks”Organic synthesis in reducing Organic synthesis in reducing

atmosphereatmosphere

The Urey-Miller Experiment The Urey-Miller Experiment (1953)(1953)

Synthesis of Adenine from Synthesis of Adenine from cyanidecyanide

•Nitriles: highly polar group (dipole: 3.9 Debye)

•Reaction: substitution (C), addition on triple bond

•Condensation catalyzed by heat (in aqueous medium)

1.16Å890kJ/mol

Synthesis of Pyrimidine Synthesis of Pyrimidine basesbases

CH4 + N2

spark

Synthesis of AldosesSynthesis of Aldoses

Aldehydes/ketones: permanent or induced Aldehydes/ketones: permanent or induced dipole (Odipole (O22 electronegativity) electronegativity)

Tautomery and H mobility on CTautomery and H mobility on C Nucleophilic additions on CNucleophilic additions on C

C=O1.24Å735kJ/mol

Peptide bonds formationPeptide bonds formation

Catalytic activity

Synthesis in non-Synthesis in non-reducing reducing

AtmosphereAtmosphere

The “Pyrite” hypothesisThe “Pyrite” hypothesis

In hydrothermal In hydrothermal sourcessources

Reduction of atm. Reduction of atm. COCO22 and N and N22

Autotrophic Autotrophic Final Final product: pyruvateproduct: pyruvate

Self-organized, Self-organized, coupled chemical coupled chemical reactions: reactions: metabolism from the metabolism from the start!start!

Deep-sea vents biotaDeep-sea vents biota

Reducing conditions in deep-sea Reducing conditions in deep-sea vents: Fe chemistry, temperature vents: Fe chemistry, temperature >350degC:>350degC: FeS + HFeS + H22S S FeS FeS22 + 2H + 2H++ + 2e + 2e--

Extreme thermophiles ribosomal Extreme thermophiles ribosomal RNA: most primitive organisms RNA: most primitive organisms known to date!known to date!

Prebiotic organics in Prebiotic organics in early Earthearly Earth

Exo-Biological sourcesExo-Biological sources

Space dust: 40000 tons/year OR 8 Space dust: 40000 tons/year OR 8 ng/cmng/cm22

Murchinson meteorite: 4.6 bY, amino Murchinson meteorite: 4.6 bY, amino acids, purines, pyrimidines, carbox. Ac., acids, purines, pyrimidines, carbox. Ac., polyols…polyols…

Carbon as a result from HCarbon as a result from H22 and He and He “burning” (fusion) in stars “burning” (fusion) in stars

What was found or not in What was found or not in meteorites or comets dustmeteorites or comets dust

Found: diverse simple organic Found: diverse simple organic molecules, membrane-forming molecules, membrane-forming aliphatic moleculesaliphatic molecules

Not found: polypeptides, Not found: polypeptides, mononucleotidesmononucleotides

The question of “chemical The question of “chemical selection”selection”

Why do Miller’s amino acids form (Why do Miller’s amino acids form (--enantiomers)?enantiomers)? -amino-acids are more thermodynamically -amino-acids are more thermodynamically

stable than stable than -amino-acids-amino-acids BUT: many molecules under kinetic controls BUT: many molecules under kinetic controls

catalysts, catalysts, i.e.i.e. enzymes! enzymes!

Enzymes first? How possible?Enzymes first? How possible?

How can selection (in Darwinian terms) How can selection (in Darwinian terms) be applied to prebiotic chemistry?be applied to prebiotic chemistry?

The example of D-ribose in The example of D-ribose in RNA/DNARNA/DNA

Why D-ribose instead of D-ribulose ?

Reasons for pre-biotic Reasons for pre-biotic selectionselection

ContingencyContingency A chemical pathway is determined by the A chemical pathway is determined by the

co-occurrence of precursors in time and co-occurrence of precursors in time and spacespace

DeterminismDeterminism Nature has “chosen” a path that leads to Nature has “chosen” a path that leads to

further developments/evolution further developments/evolution (according to the laws n Physics and (according to the laws n Physics and Chemistry)Chemistry)

The Deterministic The Deterministic hypothesishypothesis

Would a “wrong” thermodynamically Would a “wrong” thermodynamically stable chemical lead to a dead-end in stable chemical lead to a dead-end in evolution OR to an equally good evolution OR to an equally good alternative?alternative?

Hypothesis tested by Eschenmoser Hypothesis tested by Eschenmoser et al. (1986):et al. (1986): D-furanose D-furanose vsvs D-pyranose as the D-pyranose as the

“sugar” for DNA (homo-RNA)“sugar” for DNA (homo-RNA)

Eschenmoser’s homo- and Eschenmoser’s homo- and allo-DNAallo-DNA

Eschenmoser, 1999. Science, 284:2118-2124

Stability of homo-DNA Stability of homo-DNA duplexesduplexes

Greater stability due to higher rigidity of pyranose ring: pre-oganisation into helical structure

Other alternatives to D-Other alternatives to D-riboseribose

Other “potentially natural” oses Other “potentially natural” oses could give alternative DNA with could give alternative DNA with similar Tmsimilar Tm

Nature only selected D-ribose… a Nature only selected D-ribose… a matter of contingency or matter of contingency or determinism?determinism?

On the origin of Molecular On the origin of Molecular AsymmetryAsymmetry

Why only one type of chirality in families of Why only one type of chirality in families of molecules (L-form of amino-acids, D-form for molecules (L-form of amino-acids, D-form for sugars)?sugars)?

Why only one type of chirality and stereoregularity Why only one type of chirality and stereoregularity in natural polymer chains?in natural polymer chains?

Any thermodynamic reason? Only subtle Any thermodynamic reason? Only subtle differences in free energy between two forms (10differences in free energy between two forms (10-10-10 J).J).

In chemistry, often racemic mixtures are obtained!In chemistry, often racemic mixtures are obtained!

Molecular asymmetryMolecular asymmetry

See animation

Crystals as ”symmetry Crystals as ”symmetry breakers” breakers”

Achiral or racemic mixtures Achiral or racemic mixtures generally give crystals with faces of generally give crystals with faces of opposite handedness: equal opposite handedness: equal probability to interface medium probability to interface medium

The face of the crystal at interface The face of the crystal at interface with medium will induce with medium will induce racemisation of the solution (glycine racemisation of the solution (glycine crystals)crystals)

Complementarity in Complementarity in homochiralityhomochirality

Would life be possible with D-amino Would life be possible with D-amino acids?acids? Maybe, but only with L-sugars…Maybe, but only with L-sugars…

Example: topoisomerase with D-amino-Example: topoisomerase with D-amino-acids incapable to recognise right-acids incapable to recognise right-handed DNA!handed DNA!

If enzymes catalyzed sugars synthesis…If enzymes catalyzed sugars synthesis…

In SummaryIn Summary

Thermodynamic control: gives an initial set Thermodynamic control: gives an initial set of favorable products, essentially monomersof favorable products, essentially monomers

Kinetic control: responsible for the Kinetic control: responsible for the diversification (hence life), in particular diversification (hence life), in particular polymerspolymers Sequence of 129aa of lysozyme not because Sequence of 129aa of lysozyme not because

most stable combination!most stable combination!

Symmetry can be broken, but how does Symmetry can be broken, but how does asymmetry propagate? asymmetry propagate?