Self-Organizing Bio-structures

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

2. Lecture 3 Self-Organization and Emergence

3. Introduction and definitions

4. Life as the result of Self-Organization • Life appeared as result of gradual increase in molecular complexity (Chap. 3 & 4) • Happened with NO enzymatic ”intelligence” & NO DNA/RNA ”memory” • The dynamics of a system can tend by themselves to increase the inherent order of a system -Organization vs Entropy-? René Descartes (1596-1650)

5. S-O in Chemistry • self-assembly of molecules = supermolecules • reaction-diffusion systems and oscillating chemical reactions (out-of-equilibrium) • autocatalytic networks (biological evolution) • liquid crystals • See K. Nagayama’s lecture online on self-assembly (1997) at: http://www.vega.org.uk/video/programme/70

6. S-O in Biology • spontaneous folding of proteins and other biomacromolecules • formation of lipid bilayer membranes • homeostasis (the self-maintaining nature of systems from the cell to the whole organism) • morphogenesis, or how the living organism develops and grows (embryology) • the coordination of human movement • the creation of structures by social animals, such as social insects (bees, ants, termites), and many mammals • flocking behaviour (such as the formation of flocks by birds, schools of fish, etc.) • the origin of life itself from self-organizing chemical systems, in the theories of hyper cycles and autocatalytic networks • the organization of Earth's biosphere in a way that is broadly conducive to life (Gaia hypothesis) SIZE

7. The Ingredients of SO • SO is governed by Thermodynamicsie negative change in Free Energy (micelle formation) OR by Kinetics (virus envelope) • Always dictated by internal rules to the system • Regulated by Feedback (positive OR negative) • Involves multiple interactions • Is a balance between exploitation and exploration • In general leads to Emergence (new properties)

8. What is NOT SO! (whatever the scale)

9. Simple molecular systems

10. Aggregation of Surfactant molecules: a case of entropy-driven SO • In this system (depends on initial set of conditions): • Increase of local order (micelle) • Increase in global entropy (freeing of H2O molecules)

11. Detergents & Aggregates in water • Another type of order increase: compartmentation & segregation of guest molecules

12. SO of a lipidic vesicle

13. SO of wedge-shaped molecules

14. Protein folding: a case of thermodynamic control Anfinsen experiment with RNaseA, 1970

15. S-O of complex polymeric proteins A: Core of pyruvate dehydrogenase: homopolymer 24 chains C: F-actin homopolymer, 13chains/turn B: Aspartate Transcarbamoylase (ATCase), 2C3 + 3R2

16. S-O and autocatalysis

17. Increasing SO rate with time • In auto-catalytic SO processes, the rate of self-assembly increases with time • Examples: DNA duplexes, protein folding... • Further molecular interactions favored with proximity

18. Duplex formation in DNA

19. Duplex formation in t-RNA

20. Is polymerization a SO process?

21. Polymerization vs Self-Assembly • Polymerization is SO if spontaneous (nylon, acrylamide...) • Polymerization results in decrease in Entropy • Step-wise polymerisation in general not SO process

22. Di-Block Copolymers: tools for design in nanosciences

23. SO processes under kinetic control

24. Activation Energy (in enzymatic processes) E + S ES E + P

25. The folding of insulin: a case of thermodynamic and kinetic control spontaneous enzymatic

26. SO and symmetry breaking

27. J-aggregate Symmetry breaking in porphyrin aggregates • Formation of homochiral helices in a chiral hydrodynamic flow • Role of vortices in spontaneous symmetry breaking

28. Template-induced chiral SO: chiral memory • Less favourable product trapped kinetically • Interplay between thermodynamics and kinetics factors

29. Complex biological systems

30. Muscle fibers • Complex assembly of filamentous protein multimers • Thin filament + Thick filament made of protein multimers

31. A thin filament of muscle fiber: Actin • SO thermodynamically controlled

32. A thick filament of muscle fiber: Myosin myosin • Thick filament: multimer of myosin heavy chain dimer • SO thermodynamically controlled: hydrophobic interactions (coiled-coil) + electrostatics (inter-mers)

33. Bacteriophage T4 • Combination of thermodynamics and kinetics • 63 gene products Kinetic ctrl Thermodyn. ctrl

34. The axoneme of a bacterial flagellum • Result of highly regulated, sequential organization of protein substructures • Complex interplay between Thermodyn. & Kinetics

35. Model for SO of bacterium flagella(K. Namba)

36. SO in Macroscopic systems Anthill Migratory bird pattern • SO : patterns with no ordering center • Internal forces : complex genetic and social factors

37. Out-of-Equilibrium SO

38. Bénard cells & convection Apparent conflict: SO obtained far from equilibrium! Oscillating system: patterns/no patterns At bifurcation point: formation of patterns (diverse shapes)

39. The Zabotinski-Belousov reaction: Out-of-Eq reaction with periodic oscillations • Family of reactions including KBr and sulfuric acid, CeriumIV (and Ferroin) • CeIV + FeIII CeIII + FeII • Excitable: stimulus (mechanical, optical...) induces SO (patterns) from quiescent state

40. Bifurcation point & Dissipative system • The Brusselator (Prigonine, Nobel Chemistry 1977) • A (open) system pulled from Eq. reaches a point of instability (minimal entropy production) • At this point (lc) and beyond: SO occurs • Dissipative system: exchanges Energy & Matter with environ.

41. Genesis of Out-of-Eq. theory • Alan Turing (1952): system homogenous close to Equilibrium  unstable far from Eq. (fluctuations) • Prigonine & Lefever (1968): theoritical model to describe ingredients necessary for spatial SO in a system • Belousov & Zabotinsky (1950’s): complex reaction mixture to ”mimic” Krebs cycle, observation of oscillations in colour (CeriumIV / CeriumIII) and shapes

42. Characteristics of Out-of-Eq reactions • Time-dependency of system’s themodynamics • Irreversible reaction • Dynamic & non-linear

43. The notion of Emergence

44. SO and Emergence go together • Emergence can be defined as: • ”The onset of novel properties that arise when a higher level of complexity is formed from components of lower complexity, where these properties are not present” • Assumption (epistemic view): • The objects forming a complex SO system AND its levels of structures can be considered as separated

45. A simple chemical: benzene • Aromatic character of benzene not present in its atoms

46. A more complex example: Myoglobin & Hemoglobin • Myoglobin transports O2 thanks to heme group • Shows Michaelis-Menten behaviour • Hemoglobin is tetramer (chains homologous to myoglobin) • Shows Sigmoidal behaviour

47. Emergence in Geometry • New properties arise at each level of hierarchy, not present at the previous level

48. Main characteristics of Emergence in SO systems • Deducibility: The emergent property of the whole cannot be deduced from the properties of its parts • Downward causation: The properties of higher hierarchic levels affect properties of lower components • Non-linearity: SO in dissipative open-systems, far from equilibria: emergence can occur at points of instability (bifurcation points)

49. Life as Emergent property • ”Quorum sensing” in bacteria: cell density-dependent signalling mechanism in bacteria (biofilm formation, colonization, luminescence) • Complex SO patterns without localized organization centers (social insects) Vibrio fischeri (LUX gene)

50. Conclusions • SO systems under Thermodyn. Control: crystallization, micelle formation, protein folding, DNA hybrid ... • SO systems under Kinetic Control: protein biosynthesis, virus assembly, swarm intelligence • SO under Out-of-Eq. Systems: oscillating reactions, order-out-of-chaos, convection (tornadoes) • All living systems are open, far-from-Eq, dynamic, non-linearand dissipative structures • Irreversibility in evolution (Arrow of time)