Self-Organizing Self-Organizing Bio-structuresBio-structures

NB2-2009NB2-2009L.DurouxL.Duroux

Lecture 3Lecture 3Self-Organization and Self-Organization and

EmergenceEmergence

Introduction and Introduction and definitions definitions

Life as the result of Self-Life as the result of Self-OrganizationOrganization

Life appeared as result of gradual Life appeared as result of gradual increase in molecular complexity increase in molecular complexity (Chap. 3 & 4)(Chap. 3 & 4)

Happened with NO enzymatic Happened with NO enzymatic ”intelligence” & NO DNA/RNA ”intelligence” & NO DNA/RNA ”memory””memory”

The dynamics of a system can tend The dynamics of a system can tend by themselves to increase the by themselves to increase the inherent order of a system -inherent order of a system -Organization Organization vsvs Entropy-? Entropy-? René

Descartes (1596-1650)

S-O in ChemistryS-O in Chemistry

self-assembly of molecules = self-assembly of molecules = supermoleculessupermolecules

reaction-diffusion systems and oscillating reaction-diffusion systems and oscillating chemical reactions (out-of-equilibrium)chemical reactions (out-of-equilibrium)

autocatalytic networks (biological autocatalytic networks (biological evolution)evolution)

liquid crystalsliquid crystals

See K. Nagayama’s lecture online on self-See K. Nagayama’s lecture online on self-assembly (1997) at: assembly (1997) at: http://www.vega.org.uk/video/programme/70http://www.vega.org.uk/video/programme/70

S-O in BiologyS-O in Biology spontaneous folding of proteins and other spontaneous folding of proteins and other

biomacromolecules biomacromolecules formation of lipid bilayer membranesformation of lipid bilayer membranes

homeostasis (the self-maintaining nature of systems from the homeostasis (the self-maintaining nature of systems from the cell to the whole organism) cell to the whole organism)

morphogenesis, or how the living organism develops and morphogenesis, or how the living organism develops and grows (embryology)grows (embryology)

the coordination of human movementthe coordination of human movement

the creation of structures by social animals, such as social the creation of structures by social animals, such as social insects (bees, ants, termites), and many mammals insects (bees, ants, termites), and many mammals

flocking behaviour (such as the formation of flocks by birds, flocking behaviour (such as the formation of flocks by birds, schools of fish, etc.)schools of fish, etc.)

the origin of life itself from self-organizing chemical systems, the origin of life itself from self-organizing chemical systems, in the theories of hyper cycles and autocatalytic networks in the theories of hyper cycles and autocatalytic networks

the organization of Earth's biosphere in a way that is broadly the organization of Earth's biosphere in a way that is broadly conducive to life (Gaia hypothesis)conducive to life (Gaia hypothesis)

SIZ

E

The Ingredients of SOThe Ingredients of SO

SO is governed by SO is governed by ThermodynamicsThermodynamics ieie negative negative change in Free Energy (micelle formation) OR change in Free Energy (micelle formation) OR by by KineticsKinetics (virus envelope) (virus envelope)

Always dictated by Always dictated by internal rules to the systeminternal rules to the system

Regulated by Regulated by FeedbackFeedback (positive OR negative) (positive OR negative) Involves Involves multiple interactionsmultiple interactions Is a balance between exploitation and Is a balance between exploitation and

explorationexploration

In general In general leads to Emergenceleads to Emergence (new (new properties)properties)

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

Simple molecular Simple molecular systemssystems

Aggregation of Surfactant Aggregation of Surfactant molecules: a case of entropy-molecules: a case of entropy-

driven SOdriven SO In this system In this system

(depends on initial set (depends on initial set of conditions):of conditions):

Increase of local order Increase of local order (micelle)(micelle)

Increase in global Increase in global entropy (freeing of entropy (freeing of H2O molecules)H2O molecules)

Detergents & Aggregates in Detergents & Aggregates in waterwater

Another type of Another type of order increase: order increase: compartmentation compartmentation & segregation of & segregation of guest moleculesguest molecules

SO of a lipidic vesicleSO of a lipidic vesicle

SO of wedge-shaped moleculesSO of wedge-shaped molecules

Protein folding: a case of Protein folding: a case of thermodynamic controlthermodynamic control

Anfinsen experiment with RNaseA, 1970

S-O of complex polymeric proteinsS-O of complex polymeric proteins

A: Core of pyruvate dehydrogenase: homopolymer 24 chains

B: Aspartate Transcarbamoylase (ATCase), 2C3 + 3R2

C: F-actin homopolymer, 13chains/turn

S-O and S-O and autocatalysisautocatalysis

Increasing SO rate with Increasing SO rate with timetime

In auto-catalytic SO processes, the rate of In auto-catalytic SO processes, the rate of self-assembly increases with timeself-assembly increases with time

Examples: DNA duplexes, protein folding...Examples: DNA duplexes, protein folding...

Further molecular interactions favored with Further molecular interactions favored with proximityproximity

Duplex formation in DNADuplex formation in DNA

Duplex formation in t-Duplex formation in t-RNARNA

Is polymerization Is polymerization a SO process?a SO process?

Polymerization Polymerization vsvs Self- Self-AssemblyAssembly

Polymerization is SO Polymerization is SO if spontaneous (nylon, if spontaneous (nylon, acrylamide...)acrylamide...)

Polymerization Polymerization results in decrease in results in decrease in EntropyEntropy

Step-wise Step-wise polymerisation in polymerisation in general not SO general not SO processprocess

Di-Block Copolymers: tools Di-Block Copolymers: tools for design in nanosciencesfor design in nanosciences

SO processes SO processes under kinetic under kinetic

controlcontrol

Activation Energy (in enzymatic Activation Energy (in enzymatic processes)processes)

E + S ES E + P

The folding of insulin: a case The folding of insulin: a case of thermodynamic and kinetic of thermodynamic and kinetic

controlcontrol

spontaneous

enzymatic

SO and symmetry SO and symmetry breakingbreaking

Symmetry breaking in porphyrin Symmetry breaking in porphyrin aggregatesaggregates

J-aggregate

•Formation of homochiral helices in a chiral hydrodynamic flow

•Role of vortices in spontaneous symmetry breaking

Template-induced chiral SO: chiral Template-induced chiral SO: chiral memorymemory

Less favourable Less favourable product trapped product trapped kineticallykinetically

Interplay between Interplay between thermodynamics thermodynamics and kinetics and kinetics factorsfactors

Complex Complex biological biological systemssystems

Muscle fibersMuscle fibers

Complex assembly of filamentous protein Complex assembly of filamentous protein multimersmultimers

Thin filament + Thick filament made of protein Thin filament + Thick filament made of protein multimersmultimers

A thin filament of muscle fiber: A thin filament of muscle fiber: ActinActin

SO SO thermodynamically thermodynamically controlledcontrolled

A thick filament of muscle A thick filament of muscle fiber: Myosinfiber: Myosin

Thick filament: multimer of myosin heavy chain dimerThick filament: multimer of myosin heavy chain dimer

SO thermodynamically controlled: hydrophobic SO thermodynamically controlled: hydrophobic interactions (coiled-coil) + electrostatics (inter-mers)interactions (coiled-coil) + electrostatics (inter-mers)

myosin

Bacteriophage T4Bacteriophage T4

Combination of Combination of thermodynamics thermodynamics and kineticsand kinetics

63 gene products63 gene productsKinetic ctrl

Ther

mod

yn. c

trl

The axoneme of a bacterial The axoneme of a bacterial flagellumflagellum

Result of highly regulated, sequential Result of highly regulated, sequential organization of protein substructuresorganization of protein substructures

Complex interplay between Thermodyn. & Complex interplay between Thermodyn. & KineticsKinetics

Model for SO Model for SO of bacterium of bacterium

flagellaflagella(K. Namba)(K. Namba)

SO in Macroscopic systemsSO in Macroscopic systems

SO : patterns with no ordering centerSO : patterns with no ordering center

Internal forces : complex genetic and social Internal forces : complex genetic and social factorsfactors

Migratory bird patternAnthill

Out-of-Out-of-Equilibrium SOEquilibrium SO

Bénard cells & convectionBénard cells & convection

Apparent conflict: SO obtained far from equilibrium!Oscillating system: patterns/no patternsAt bifurcation point: formation of patterns (diverse shapes)

The Zabotinski-Belousov reaction: The Zabotinski-Belousov reaction: Out-of-Eq reaction with periodic Out-of-Eq reaction with periodic

oscillationsoscillations

Family of reactions including KBr and sulfuric Family of reactions including KBr and sulfuric acid, CeriumIV (and Ferroin)acid, CeriumIV (and Ferroin) CeIV + FeIIICeIV + FeIII CeIII + FeIICeIII + FeII

Excitable: stimulus (mechanical, optical...) Excitable: stimulus (mechanical, optical...) induces SO (patterns) from quiescent stateinduces SO (patterns) from quiescent state

Bifurcation point & Dissipative Bifurcation point & Dissipative system system

The Brusselator (Prigonine, The Brusselator (Prigonine, Nobel Chemistry 1977)Nobel Chemistry 1977)

A (open) system pulled from A (open) system pulled from Eq. reaches a point of Eq. reaches a point of instability (minimal entropy instability (minimal entropy production)production)

At this point (At this point (c) and beyond: c) and beyond: SO occursSO occurs

Dissipative system: Dissipative system: exchanges Energy & Matter exchanges Energy & Matter with environ.with environ.

Genesis of Out-of-Eq. Genesis of Out-of-Eq. theorytheory

Alan Turing (1952): system homogenous close to Alan Turing (1952): system homogenous close to Equilibrium Equilibrium unstable far from Eq. (fluctuations) unstable far from Eq. (fluctuations)

Prigonine & Lefever (1968): theoritical model to Prigonine & Lefever (1968): theoritical model to describe ingredients necessary for spatial SO in a describe ingredients necessary for spatial SO in a systemsystem

Belousov & Zabotinsky (1950’s): complex reaction Belousov & Zabotinsky (1950’s): complex reaction mixture to ”mimic” Krebs cycle, observation of mixture to ”mimic” Krebs cycle, observation of oscillations in colour (CeriumIV / CeriumIII) and oscillations in colour (CeriumIV / CeriumIII) and shapesshapes

Characteristics of Out-of-Eq Characteristics of Out-of-Eq reactionsreactions

Time-dependency of system’s Time-dependency of system’s themodynamicsthemodynamics

Irreversible reactionIrreversible reaction

Dynamic & non-linearDynamic & non-linear

The notion of The notion of Emergence Emergence

SO and Emergence go SO and Emergence go togethertogether

Emergence can be defined as:Emergence can be defined as: ””The onset of novel properties that arise The onset of novel properties that arise

when a higher level of complexity is formed when a higher level of complexity is formed from components of lower complexity, from components of lower complexity, where these properties are not present”where these properties are not present”

Assumption (epistemic view):Assumption (epistemic view): The objects forming a complex SO system The objects forming a complex SO system

AND its levels of structures can be AND its levels of structures can be considered as separatedconsidered as separated

A simple chemical: benzeneA simple chemical: benzene

Aromatic character of benzene not Aromatic character of benzene not present in its atomspresent in its atoms

A more complex example: A more complex example: Myoglobin & HemoglobinMyoglobin & Hemoglobin

Myoglobin transports Myoglobin transports OO22 thanks to heme thanks to heme groupgroup Shows Michaelis-Shows Michaelis-

Menten behaviourMenten behaviour

Hemoglobin is tetramer Hemoglobin is tetramer (chains homologous to (chains homologous to myoglobin)myoglobin) Shows Sigmoidal Shows Sigmoidal

behaviourbehaviour

Emergence in GeometryEmergence in Geometry

New properties New properties arise at each level arise at each level of hierarchy, not of hierarchy, not present at the present at the previous levelprevious level

Main characteristics of Main characteristics of Emergence in SO systemsEmergence in SO systems

DeducibilityDeducibility: The emergent property of the : The emergent property of the whole cannot be deduced from the properties of whole cannot be deduced from the properties of its partsits parts

Downward causationDownward causation: The properties of higher : The properties of higher hierarchic levels affect properties of lower hierarchic levels affect properties of lower componentscomponents

Non-linearityNon-linearity: SO in dissipative open-systems, : SO in dissipative open-systems, far from equilibria: emergence can occur at far from equilibria: emergence can occur at points of instability (bifurcation points)points of instability (bifurcation points)

Life as Emergent Life as Emergent propertyproperty

””Quorum sensing” in bacteria: cell Quorum sensing” in bacteria: cell density-dependent signalling mechanism density-dependent signalling mechanism in bacteria (biofilm formation, in bacteria (biofilm formation, colonization, luminescence)colonization, luminescence)

Complex SO patterns without localized Complex SO patterns without localized organization centers (social insects)organization centers (social insects)

Vibrio fischeri (LUX gene)

ConclusionsConclusions SO systems under Thermodyn. Control: crystallization, SO systems under Thermodyn. Control: crystallization,

micelle formation, protein folding, DNA hybrid ...micelle formation, protein folding, DNA hybrid ...

SO systems under Kinetic Control: protein biosynthesis, SO systems under Kinetic Control: protein biosynthesis, virus assembly, swarm intelligencevirus assembly, swarm intelligence

SO under Out-of-Eq. Systems: oscillating reactions, order-SO under Out-of-Eq. Systems: oscillating reactions, order-out-of-chaos, convection (tornadoes)out-of-chaos, convection (tornadoes)

All living systems are open, far-from-Eq, dynamic, non-All living systems are open, far-from-Eq, dynamic, non-linearand dissipative structureslinearand dissipative structures

Irreversibility in evolution (Arrow of time)Irreversibility in evolution (Arrow of time)

Literature for analysisLiterature for analysis Bucknall & Anderson, 2003Bucknall & Anderson, 2003 Zeng et al, 2004Zeng et al, 2004 Purello, 2003Purello, 2003