Self-Organizing Bio-structures

1. Self-Organizing Bio-structures NB2-2009 L. Duroux

2. 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/self-assembly of bio-structures: molecules to supra-molecular assemblies

3. SO & physics Diffusion-limited Aggregation Snowflake Benard Convection Cells Sand Dune

4. SO & chemistry micelle DNA keratin & collagen Simplex virus

5. SO & Biology Slime mold Nautilus Daisy Zebra

6. SO & Nanotechnology Liquid crystals Dendrimers Bacterio-rhodopsin DNA tiles

7. Supramolecular Chemistry • Jean-Marie LEHN (Nobel Chemistry, 1987) • Chemistry beyond molecules  Supermolecules • Organization, intermolecular non-covalent bonds, different (better) properties than parts

8. Lecture Plan • 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

9. 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 3-540-01298-2) • Selected review articles on specialized topics

10. 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., HardcoverISBN: 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

11. Lecture 1 From Pre-Biotic Chemistry to Macromolecular Assemblies

12. A scale of Molecular Complexity towards Life CELLS METABOLIC NETWORKS POLYMER COMPLEXES MACROMOLECULES BIOMONOMERS MOLECULES ATOMS

13. The origin of Life: a time scale

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

15. Formation of organic molecules “building blocks” Organic synthesis in reducing atmosphere

16. The Urey-Miller Experiment (1953)

17. Synthesis of Adenine from cyanide • Nitriles: highly polar group (dipole: 3.9 Debye) • Reaction: substitution (Ca), addition on triple bond • Condensation catalyzed by heat (in aqueous medium) 1.16Å 890kJ/mol

18. Synthesis of Pyrimidine bases CH4 + N2 spark

19. 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

20. Peptide bonds formation Catalytic activity

21. Synthesis in non-reducing Atmosphere

22. 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!

23. 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!

24. Prebiotic organics in early Earth

25. 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

26. What was found or not in meteorites or comets dust • Found: diverse simple organic molecules, membrane-forming aliphatic molecules • Not found: polypeptides, mononucleotides

27. The question of “chemical selection” • Why do Miller’s amino acids form (a-enantiomers)? • a-amino-acids are more thermodynamically stable than b-amino-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?

28. The example of D-ribose in RNA/DNA Why D-ribose instead of D-ribulose ?

29. Reasons for pre-biotic selection • Contingency • A chemical pathway is determined by the co-occurrence 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)

30. 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)

31. Eschenmoser’s homo- and allo-DNA Eschenmoser, 1999. Science, 284:2118-2124

32. Stability of homo-DNA duplexes Greater stability due to higher rigidity of pyranose ring: pre-oganisation into helical structure

33. 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?

34. 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!

35. Molecular asymmetry • See animation

36. 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)

37. 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…

38. 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?