NORCIA LUGLIO 2005:

SELF-REPRODUCTION OF

SYNTHETIC SYSTEMS

(AS MODELS FOR BIOLOGICAL

SELF-REPLICATION)

THE INCREASE OF COMPLEXITY

TOWARDS THE EMERGENCE OF LIFE

PROCEEDS

VIA THE INTERPLAY

BETWEEN

SELF-ORGANIZATION AND

EMERGENCE

SELF-ORGANIZATION: THE

ACQUISITION OF HIGHER

STRUCTURAL ORDER-AS

DETERMINED BY THE

SYSTEM’S RULES

…under thermodynamic

or kinetic control

Emergence:

the formation of a higher

complexity level brings about

NOVEL properties

that are not present

in the basic components

..the whole is more

than the sum of

the parts

...holism

ORIGIN OF SELF - REPRODUCTION

ORIGIN OF LIFE

" self " meansthat the structure itself does iti. e. , the process is autocatalytic

self - reproduction = autocatalysis

AND :

AND :

IF THE STRUCTURE CARRIES INFORMATION (A) ,THEN WE HAVEREPRODUCTION & INFORMATION AT A TIME

IF DURING SELF-REPRODUCTIONALSO STRUCTURAL ( FUNCTION ) CHANGES OCCUR,WE ALSO HAVE EVOLUTION NOVEL CATALYSIS

.....everything else

A-DNA B-DNA Z-DNA

pairing of chromsomes

and crossing over of

chromosomes does

occur

pairing of chromsomes

does not occur

chromosome

pairs align at

metaphase plate

chromosome align

independently

homologous

chromosomes

separate

daughter

chromosomes

separate

daughter

chromosomes

separate

daughter cells are not genetically

identical to parent cells

daughter cells are genetically

identical to parent cells

Comparison of meiosis

and mitosis.

(The blue chromosomes

were inherited from one

parent, and the red

chromosomes were

inherited from other

parent.)

(from Biology / S.Mader, 5th ed.)

Original parent molecule

First generation daughter molecules

Second generation daughter molecules

Schematic diagram of semiconservative

replication. Parental DNA is shown in green

and newly synthesized DNA in red.

[After M. Meselson and F.W . Stahl.Proc. Nat. Acad. Sci. 44(1958):671.)

parent molecule

new

strandold

strand

daughter moleculedaughter molecule

old

strandnew

strand

DNA Double Helix________________________

Sugar: Deoxyribose

Bases: Adenine (A), guanine (G)

thymine (T), cytosine (C)Strands: Double stranded with base

pairing

sugar-phosphate

backbone

sugar

hydrogen bonds

complementarybase pairing

2nm

0.34nm 3.4nm

In particular research focusses on

SELF-REPLICATION SYSTEMS

Self means that the process is spontaneous, i.e.,

determined by the internal rule of the system

(generally self-replication corresponds to

autocatalysis, and generally the

time process is exponential)

A 2A 4A 8A 16A etc

Origin of life

from self-replicating molecules

(how it works on paper)

a) heterocatalysis

A B

One molecule per second, then 6.1023 sec. to make

one mole of B

b) self-replication (autocatalysis)

A A

Only 79 sec. to make one mole of A

2.....4.....8.....16.....32.....64.....128......etc.

DNA Double Helix________________________

Sugar: Deoxyribose

Bases: Adenine (A), guanine (G)

thymine (T), cytosine (C)Strands: Double stranded with base

pairing

sugar-phosphate

backbone

sugar

hydrogen bonds

complementarybase pairing

2nm

0.34nm 3.4nm

A B

M

D

T(2x)

K 1

kK2

General mechanism for a minimal self-replicating system.

Constituent A represents the activated form of trimer A2 here.

Large arrowheads at the reaction arrows for the reversiblereactions indicate the favored site of the equilibrium.

Kiedrowski, Angew.chem. (1986) 10, 932

Rebek, JACS (1990)

the notion of hypercycle, originally developed by Eigen and

collaborators (Eigen 1971, Eigen and Schuster 1977, 1979).A simple rendering of an hypercycle,

Fig. 4.6 The hypercycle. Each of the units A, B, C and D is a replicator. The rate of replication of each

unit is an increasing function of the concentration unit immediately preceeding it. Thus the rate of

replication of B is an increasing function of the concentration of A, and so on round the cycle.

Micelle

Liposome

Bilayer sheet

Cross-sectional views of the three structures that can be formed by

mechanically dispersing a suspension of phospholipids in aqueous solution

The red circles depict the hydrophilic heads of phospholipids, and

the squiggly lines (in the yellow region) the hydrophobic tails.

O

OH

O

O

OP

O

O

HO

O

ON+

NO

OH

N

O

OH

O NH2

O

O

O

O

OP

O

O

H

Oleic acid / oleat vesicles

SELF-REPRODUCING MICELLES, LIPOSOMES

& CHEMICAL AUTOPOIESIS

etc.....

SELF - REPLICATING MICELLES

H2O

S

A ,B

S S S S SS

SSS

S

S

S

SS

S

S

SS

SS

SS S S S S

A A

A

A

A B S+

B B

B

B

S

S S SS

SS

SS

S

SS

S

SS

S

SS

S

S

S S

S S S SS

A A

A

A

A B S+

B B

B

B

S S

S

SS

S

SS

S

S

S

S

S

S

SS S S S S

SS

SS

S

S

S

SS

S

S

SS

SS

SS S S S S

A A

A

A

A B+

B B

BB

SS S S S S

SS

SS

S

S

S

SS

S

S

SS

SS

SS S S S S

A A

A

A

A B+

B B

BB

waterpool

bulk solvent

etc.

etc.

LUISI & VARELA

ORIGIN OF LIFE 1990

a

b

caprylate COO-

oleate

or

CH3(CH2)7 -CH = CH-(CH2)7COO-

form micelles at alkaline pH

COO-

(Deamer, 1976)

vesicles at pH=7-8

(pH pk)~_

COO- HOOC

precursors ( water insoluble! )

R CO

R COO

OH-

OH-

R COOR'

or

micelles or

R COO-

vesicles

... a reaction which creates its ownmicroenvironment for self-replication....

water insolubleETHYL CAPRYLATE

NaOH

H2O

Ethylcaprylate caprylatecmcOH-

micelles in water

(pH ~ 10)

or vesicles (pH ~ 7 - 8)

(start with anhydride)

.

1.5

1.2

0.9

0.3

0.0

0.6

0 10 20 30 40

1.5 M EC

3 M NaOH

water

caprylate

biphasic System clear micellarsolution

Ethylcaprylate

( EC )

Caprylate + EtOH

100 C

OH-

ECEC

ECECOH-

Caprylatecmc

micelles

EC

accelleratedhydrolysisof EC

more micelles(self-replication)

MIC[ ]

3 mM

2 mM

1 mM

Capry

late

(M

)

time (h) Nature 357 (1992) 57

Hydrolysis of Caprylic anhydride

13

11

9

7

5

0 100 200 300 400 500

Time ( hrs )

CA

pH

CAcac

CA

CA

CACA

CA CA

CA

morevesicles

fast CAhydrolysis

T = 40 °C

The hydrophobicity of the lipid bilayer

Is the main driving force for

The activity/reactivity and applications

Of liposomes

SS

SS

SSH2O

SS

S

excesswater-insolublesurfactant precursorbound to the bilayer

hydrolyzedon / bythe bilayer

largerunstableintermediates

forming moreof smaller stable vesicles

S

SS

SS

S

SS

S

S

S

S

S

H2O

S

S

SS

SS S

S

H2O S

lipophilic bilayerof surfactant S

S

SS

SS S

S

H2O S

S

SS

SS S

S

H2O S

s-s

s-s