Physical Chemistry of Natural Selection

8/4/2019 Physical Chemistry of Natural Selection

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Physical chemistry of natural

selection

Jean-Louis Sikorav

EPFL October 9 2008


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Approaches of natural

selectionFormal (based on logic, mathematics,

geometry, genetics) such as Genetical

Theory of Natural Selection (RA Fisher). Thishas an underlying materialistic basis: The

physical chemistry of natural selection

Other (higher) levels exist: cell, unicellular

vs mult icellular organisms, species,populations


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Physical chemistry of natural

selection

How do we understand the high yields

and the high rates of biochemistry?

Partial answer: a relation between

efficiency and heterogeneity,

macroscopic or microscopic (chiralityand polarity).


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Macroscopic heterogeneity:

Homogeneous versusheterogeneous biochemistry


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Homogeneous and

heterogeneous chemistry

The field of chemistry is commonly divided into two parts,

namely homogeneous and heterogeneous chemistry.

Homogeneous chemistry deals with the study of chemicalprocesses taking place in the bulk of a homogeneous phase,

such as a gaseous, a liquid (a solution) or a solid phase.

Heterogeneous chemistry is concerned with the investigation

of chemical processes that involve more than one phase

(either more than one phase at the onset of the process or acoupling between the process and a phase transition/phase

separation).


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The birth of physical chemistry:

heterogeneity as a nuisance

(vant Hoff)

Les mlanges homognes, les mlanges gazeux et les

solutions jouent souvent un rle prpondrant dans les

phnomnes dquilibres chimiques (1898)

Ce sont les ractions dquilibre des mlanges homognes

qui prsentent le plus dintrt (1898)

Lhtrognit est une nuisance , quil est possibledliminer, par exemple par humectation des

parois (Etudes de dynamique chimique, 1884)


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Importance of solutions:Arrhenius, The Theory of Solutions, 1912

"The liquid state was already at that time (The Middle

Ages) found to be the most suitable condition forchemical reactions.

The experience of the alchemists was summed up

under the formula "the Substances do not act upon

each other unless they are dissolved" (corpora nonagunt nisi soluta).


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Homogeneous and

heterogeneous biochemistry

In a similar way one can define a homogeneous anda heterogeneous biochemistry.

The scope of homogeneous biochemistry can benarrowed down to the study of biochemical processestaking place in the bulk of a homogeneous aqueousphase (an aqueous solution).

The goal of this lecturewill be to define and to explorethe field of heterogeneous biochemistry, with anemphasis on the heterogeneous biochemistry ofnucleic acids.


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The two meanings of

homogeneous biochemistryExperimental meaning: the study of processes takingplace in the bulk of a water solution.

Theoretical meaning: that a water solution can be

described as a homogeneous mass, which is only truefor a limited range of length and temporal scales.According to this point of view, a water solution can bedescribed using scalar (directionless), extensivevariables, and this simplifies its description.

Our focus in this presentation will be on the

experimental meaning and on bulk, macroscopichomogeneity/heterogeneity.

(Microscopic heterogeneity: chirality and polarity)


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Outline of the presentation

1. Historical background.2. A case study in heterogeneous biochemistry: DNA

cyclization and renaturation.

3. General concepts.4. Conclusions.


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A search for the relevant

literature

A search for the exact terms heterogeneousbiochemistry in several bibliographical databases(Pub Med: 1950-present; Chemical Abstracts: 1907-present; Science Citation Index 1945-present)completed by an internet search (Google, Scirus) isnegative.

In contrast with the field of heterogeneouschemistry for which there exists a rich literature, the

field of heterogeneous biochemistry has apparentlynever been reviewed.

Why?


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Why?

First possibility:

No one has ever discussed the role of phaseheterogeneity in biochemistry. There is no referencebecause this is a completely new concept.

This conclusion is incorrect.


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A history of homogeneous and

heterogeneous biochemistry (1) What are the concepts required to define

homogeneous and heterogeneous biochemistry?

In addition to the concepts of chemistry and

physiological or biological chemistry (mid 19thcentury: Hoppe-Seyler and others), we need theconcepts of homogeneity and phase.

When were these concepts introduced?Homogeneity: very old (Anaxagoras: see the article

Atoms by Maxwell in the Encyclopedia Britannica )Phase and phase coexistence: Gibbs (1875)


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J. Willard Gibbs. On the equilibrium of heterogeneous

substances. Transaction of the Connecticut Academy,

(1875-1876) vol. 3, pp. 108-248.

Let us first consider the energy of any homogeneous part of agiven mass, and its variation for any possible variation in thecomposition and state of this part. (By homogeneous is meant thatthe part of question is uniform throughout, not only in chemicalcomposition but also in physical state).

In considering the different homogeneous bodies which can beformed out of any set of component substances, it will beconvenient to have a term which shall refer solely to thecomposition and thermodynamic state of any such body withoutregard to its quantity or form. We may call such bodies as differ incomposition of state different phases of the matter considered,

regarding all bodies which differ only in quantity and form asdifferent examples of the same phase. Phases which can existtogether, the dividing surfaces being plane, in an equilibrium whichdoes not depend upon passive resistances to change, we shall callcoexistent.


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A new search for the relevant

literatureBooks on History of Chemistry and Biochemistry(Fruton, Florkin, Laszlo)

Old text books on chemistry (vant Hoff, Arrhenius)

and biochemistry (Enzymes: Bayliss, Haldane,Sumner)

JSTOR, Bibliothque Nationale de France (Gallica),

Web site of the Nobel Foundation

This search is not completed (language barrier).


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heterogeneous biochemistry (2) Any researcher having read Gibbs is able to discuss

the relevance of the ideas of homogeneity/heterogeneity and phase for biochemistry.

Who was the first scientist to do it? A difficult question, with often no simple answer

(see TS Kuhn, Historical Structure of ScientificDiscovery, Science, 1962).

The relevance of the ideas of homogeneity/heterogeneity and phases for biochemistry is alreadyclearly understood in the beginning of the 20thcentury.


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heterogeneous biochemistry (3)

Many of the most important processes of normal life occur inheterogeneous systemsSvante Arrhenius, Immunochemistry (1907). Chapter III. Velocity ofReaction. Heterogeneous systems, p.136.

Even a hasty consideration of the arrangements present in living cells issufficient to bring conviction that the physical and chemical systemsoperate under conditions very different from those of reactions takingplace between substances in true solutions. We become aware of thefact that there are numerous constituents of the cell which do not mixwith one another. In other words, the cell system is one of manyphases to use the expression introduced by Willard Gibbs.

W. M. Bayliss. The physiological importance of phase boundaries.Science (1915) vol. 42, pp. 509-518.


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Wtrich, Nobel Lecture 2002:

"Nuclear magnetic resonance (NMR) spectroscopy is

unique among the methods available for three-dimensional structure determination of proteins andnucleic acids at atomic resolution, since the NMR datacan be recorded in solution. Considering that bodyfluids such as blood, stomach liquid and saliva are

protein solutions where these molecules perform their physiological functions, knowledge of the molecularstructures in solution is highly relevant.


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A puzzling situation

The importance of the ideas of homogeneity/

heterogeneity and of phases for biology andbiochemistry is well understood in the beginning of the20th century. These ideas are not discussed afterWorld War II.

Question: What happened?

A plausible answer is that the discussion of these ideaswas premature at that time.


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States of matter

(macroscopic phases) in 1875

1 Solid state

2 Liquid state

3 Gaseous state


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States of matter today

(classical macroscopic phases)

1 Solid state

Amorphous (glass)

Crystalline

2 Fluid state

Isotropic

Anisotropic (mesomorphous, liquid crystals,

amphiphiles)

3 Gaseous state4 Polymers


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Phase transitions in biopolymers

helix-coil, coil-globule, coil-stretch,

adsorption, threading through a pore.

sol-gel, aggregation, liquid-crystalline

states.

Flory J. Pol. Sci. (1961), DiMarzio (1999)


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Biopolymers

Answer:

Our understanding that proteins and nucleic acids arepolymers is essentially posterior to World War II.

Early discussions concerning the polyphasic nature ofcells became associated with the obscure concept of acolloidal state of biological matter (Bayliss, Bancroftthe Phase Ruler ).

This contributed to discredit such generalconsiderations after 1945.

Physical Chemistry from Ostwald to Pauling: TheMaking of a Science in America. John W. Servos(1991)


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The origins of homogeneous or

solution biochemistry

1. The controversy between Pasteur and Liebig, andits solution by Buchner in 1897.

2. An application of Occams razor or parsimonyprinciple.

3. A persistent belief that (bio)chemical reactions caneither only take place in the bulk of a solution, orare more efficient in solutions.


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solution biochemistry (1)

1. A controversy on the nature of biological catalysts (nowcalled enzymes following Khne, 1876): according toPasteur les vrais ferments (enzymes) sont des tresorganiss (in other words the catalytic action requires the

presence of the entire living cell and cannot be observedwith soluble substances). This is not true according toLiebig and others (Berthelot). Pasteur has a strict holistic(vitalistic) attitude, while Liebig has a more pragmatic,reductionist approach.

In 1897 Buchner grinds yeast cells and presses them with ahydraulic press. The resulting (cell-free) press juice is ableto ferment sucrose.


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At the same time as Pasteur earned for himself undying fame by hisbrilliant exposition of the significance of living beings as the ultimatecause of such processes, he put a brake on the progress of science inthis field by the vitalistic concept of the actual course of fermentation.

Presentation Speech for The Nobel Prize in Chemistry 1907

Avec des tissus ou des cellules entires, il est souvent difficile, etparfois mme impossible, de faire pntrer certains composs travers la membrane de la cellule. Avec les extraits, au contraire, ildevient relativement ais dintervenir dans une raction Il nest pasexagr de dire que, depuis lors, lanalyse dextraits sans cellule

constitue la mthode principale des chimistes qui tudient les tresvivants. Ainsi sindividualise au dbut de ce sicle, une branchenouvelle de la chimie, la chimie biologique

Franois Jacob, La logique du vivant (1970)


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Enzymatic approach to the problem of DNA replication

Although we have in the Watson and Crick proposal a mechanical model ofreplication, we may at this point pose the question: "What is the chemicalmechanism by which this super molecule is built up in the cell?" Some sixtyyears ago the alcoholic fermentation of sugar by a yeast cell was a "vital"process inseparable from the living cell, but through the Buchner discovery of

fermentation in extracts and the march of enzymology during the first half of thiscentury, we understand fermentation by yeast as a, now familiar, sequence ofintegrated chemical reactions. Five years ago the synthesis of DNA was alsoregarded as a "vital" process. Some people considered it useful for biochemiststo examine the combustion chambers of the cell, but tampering with the verygenetic apparatus itself would surely produce nothing but disorder. Thesegloomy predictions were not justified then, nor are similar pessimistic attitudes

justified now with regard to the problems of cellular structure and specializedfunction which face us. High adventures in enzymology lie ahead and many ofthe explorers will come from the training fields of carbohydrate, fat, amino acidand nucleic acid enzymology.

Arthur Kornberg Nobel Lecture 1959


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solution biochemistry (4)2. An application of Occams razor or parsimony

principle.

J. H. Northrop. Annu. Rev. Biochem. (1961), vol. 30

pp. 1-10.

An aqueous solution is a simpler system than a

multiphasic system (less components). Thetheoretical study of phenomena in (dilute) solutions

is also easier: one can often assume a

thermodynamic ideal behavior; the kinetic analysisof the phenomena is also facilitated.


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solution biochemistry (5)3. An old and persistent beliefthat (bio)chemical reactionscan only take place in the bulk of a solution (or are moreefficient in solutions).

Corpora non agunt nisi soluta

Compounds do not act unless solubilized.

Water is the deus ex machina of alchemy, the wonderfulsolvent, the word solutio being used equally for a chemical

solution and for the solution of a problem.C.G. Jung Psychology and Alchemy


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The experiments of Buchner have played a central role in thefoundation of modern enzymology and metabolism.

Most biological chemistry or biochemistry is understood and

taught today as an aqueous solution biochemistry.See the textbooks of Jencks, Fersht, Stryer, Lehninger. Thisis especially true for the study of nucleic acids (Cantor andSchimmel, Bloomfield, Crothers and Tinoco)

An important exception concerns membrane biochemistry.See P. B. Mitchell (Nature, 1961; J. Gen. Microbiol. 1962;Nobel lecture 1978, Eur.J. Biochem. 1979).


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Case studies

1. DNA cyclization2. DNA renaturationin homogeneous and heterogeneous systems


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DNA cyclization in homogeneous and

heterogeneous systems

Bacteriophage DNA: 50,000 base pair long double-stranded DNA (dsDNA), terminated by 12 base long

single-stranded (ssDNA) complementary (cohesive)ends.

Linear in the head of the bacteriophage.

Becomes circular in a few minutes after its injection inEscherichia coli.


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E. coli

Cyclization

in a few

minutes

Cyclization

in a few

hours

0,05 m

1 m

1 m


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DNA cyclization in homogeneous systems

(Wang & Davidson 1966-1968)

Cyclization of the random coil form of phage DNA(in water, in the presence of monovalent salts).

L

C orL + L

L2

Cyclization and multimerization are competingreactions. One must use dilute chain concentrations(typically 5 g/ml or lower) to have a high yield of

circles.The rate of the reaction is too slow (4.6 10-5 s-1 inthe presence of 2M NaCl 25 C ) to account for therapidity of the reaction in vivo.


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DNA cyclization in homogeneous systems

(Wang & Davidson 1966-1968)

Measurement of the cyclization probability by comparingwith a bimolecular reaction:

1/2 left L + 1/2 right LL

J factor (for Jacobson-Stockmayer) or effectiveconcentration of about 6 10-10 M.


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Cyclization of globular DNA


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in the presence of a condensing agent

(spermidine 3+

) Using extremely dilute solutions (50 ng/ml) because

of the presence of a fast (diffusion controlled)aggregation (a phase separation) process. (Rugli Ziegler)

Fast collapse of the chain (on the millisecond timescale) for1.5 mM spermidine. Final state: a toroidalstate, an intramolecular liquid crystal.

Very fast rates (1.4-2 s-1 at 1.5 mM spermidine)involving collapsed chains. Compatible with in vivorates of cyclization.

Jary & Sikorav. Biochemistry. 1999. 38:3323-3327.


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0

100

200

300

400

0,1 1 10 100 1000

0,1 1 10 100

1 m 0,1 m

Electron

microscopy

coil globule

Sedimentation

Cyclization rateCspd

3+

Cspd3+


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in the presence of a condensing agent

(spermidine 3+

)Measurement of the cyclization probability bycomparing with a bimolecular reaction:

L + O

LO

O: a 12base longoligonucleotide complementary tothe right cohesive end of DNA.

Jfactor of about 6 10-6 M in the presence of 1.5 mMspermidine (105 larger than in the random coil state).


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2. Thermal DNA renaturation

(homogeneous)

Using dilute or very dilute

solut ions (below the

overlap concentration C*)

Bimolecular reaction:

k2rates in M-1 s-1

Thermal renaturation takes place in the bulk of

an aqueous solution in the presence of

monovalent salts and belongs to homogeneousbiochemistry.


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Coupling renaturation with aggregation

Sikorav and Church (1991)


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DNA renaturation in the presence of

a condensing agent (spermine 4+)

25000 fold faster than thermal renaturation at room temperaturefor short chains. Rates are more compatible with a diffusion-controlled process (Smoluchowski).

Addition of the condensing agent (e.g. spermine) to a verydilute solution of denatured DNA chains. Renaturation takesplace at the same time as an aggregation process:simultaneous attraction of the like and of the complementarystrands. The aggregated state is anisotropic.

Sikorav & Church. J Mol Biol. 1991, 222:1085-108.Pelta, Livolant & Sikorav. J Biol Chem. 1996, 271:5656-62.

Chaperon & Sikorav. Biopolymers. 1998, 46:195-200.


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P.E.R.T ( Phenol Emulsion Reassociation Technique)

(Kohne et al., Biochemistry, 1977)

DNA renaturation in a two-phase system:

PERT

Water + Salt+ denatured

DNA

Phenol

Continuous and vigorous shaking


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Hypotheses

The reaction involves a transient adsorption of ssDNAchains at the water-phenol interface

DNA renaturation takes place at the water-phenol interfaceGoldar & Sikorav. Eur. Phys. J. E. 2004, 14:211239.

Use a decoupling scheme to studyindependently adsorption and renaturation


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Adsorption of ssDNA3'

5'32P

NaCl + 10 mM Tris

+ 1 mM EDTA

Phnol satur en tris

Vigorous andcontinuous shaking

Centrifugation

1 min

Quantify the radioactivity

in the aqueous and the organic phases


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Partitioning of ssDNA as a

function of NaCl. I(dsDNA partitions entirely in the aqueous

phase in these conditions)

0,0 0,5 1,0 1,5 2,0 2,5 3,0

0

20

40

60

80

100

Partitionde118-(%)

CNaCl

(M)


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Adsorption of ssDNA at the

water (+ 0.85 M NaCl)-phenol

interface II

0 20 40 60 80 100 120

0

1

2

3

4

5

6

7

hauteur(cm)

Nombre de coups


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Reversibility of the adsorption

0,0 0,2 0,4 0,6 0,8 1,0

0,0

0,2

0,4

0,6

0,8

1,0

Fraction

de

118+d

ans

la

phase

aqueuse

CNaCl

(M)

Reversible adsorption at lowsaltIrreversible adsorption at highsalt

No desorption at 0.85M NaCl

The hysteresis is due to a

different partitioning of NaCl inthe two phases

0,0 0,5 1,0 1,5 2,0 2,5 3,0

1,00

1,02

1,04

1,06

1,08

1,10

1,12

1,14

1,16

(

g.cm-3)

CNaCl

(M)

TE*1 satur en phnolPhnol satur en Tris


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Desorption by the complementary

strand at 0.85 M Na Cl (1)

Agitation continueet vigoureuse

La phaseaqueuse est

prleve

On ajoute une phaseaqueuse avec la mmeconcentation en NaClet du brin complmentaire des concentrationsvaries

Agitation continue

et vigoureuse


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Desorption by the complementary

strand at 0.85 M Na Cl (2)

0 4 8 12 16 20

0

10

20

30

40

50

60

70

80

0,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5

0

10

20

30

40

50

60

70

CssDNA

(ng.ml-1

)

D

sorptionde118-(%)

D

sorptionde118-(%)

CssDNA

(ng.ml-1

)

The desorbed material isdoubled-stranded

A stoichiometric process

An interfacial reaction


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Renaturation without shaking

(1)

( ) ( ) ( )003

2

1

1ln2

32 ttt

D

D

V

R

R

tdsDNA

d

d

s

dsDNA

+

+

=

Two possible paths:

1-2-3 Eley Rideal 1-2-2-3 Langmuir-

Hinshelwood

1

2

3 1'

2'2"

Phnol

Phase aqueuse

R t ti ith t h ki


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(2)

0 20 40 60 80 100 120

0

15

30

45

60

75

90

0

15

30

45

60

75

90

118-adsorb(%)

(Temps)1/2

(s1/2

)

ADNrenatur(%)

0 2000 4000 6000 8000 10000 12000 14000 1600010

15

20

25

30

35

40

ADNrenatur(%)

temps (s)

+

1ln2

1

2

R

R

D

s

d

(cm2.s-1)

( )0t

dsDNA

Parameters t0

(s)

values 1.7 10-10 3.5 10-12 3390 58.5 0.28 2 10-3

D2d ~ 3.6 10-9 6 10-10 cm2.s-1


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(3)

SURFACE DIFFUSION VERSUS BULK DIFFUSION:

Here D2d (~ 3.6 10-9 6 10-10 cm2.s-1) is 60 timessmaller than D3d (~ 2.4 10

-7 9.6 10-9).

In other systems (diffusion of dsDNA on mica) D2d is106 times smaller than D3d (Guthold et al. Biophys. J.

77, 2284-2294, 1999).


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Adsorption with vortexing (1)

Competition between diffusion andconvection

Increase of the interfacial area

0 20 40 60 80 100 120

50

55

60

65

70

75

80

85

90

95

100

2400 rpm1800 rpm1400 rpm1200 rpm1000 rpm

118-adsorb(%)

Temps(s)


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Renaturation with vortexing (2)

2400 rpm

k2 ~ 4.2 1010 M-1.s-1

0 5 10 15 20 25 30

0

10

20

30

40

50

60

70

ADNrenatur(%)

Temps(s)

0 5 10 15 20 25 30

1

2

3

1/fss

temps (s)

PERT is an interfacial reactionReaction takes place during thecoalescence of phenol droplets


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Comparing PERT with other systemsNucleic acid Reaction medium Temperature k2

(M-1s-1)

Reference

Intact Phage 7 DNA

(39.9 kb)

0.1 mM buffer, pH 8

40 mM NaCl

25 C 4 104 Studier (1969)

Intact Phage 7 DNA(39.9 kb)

0.1 mM buffer, pH 8

60 mM NaCl

35 C 6 105 Studier (1969)

Intact Phage 7 DNA

(39.9 kb)

0.1 mM buffer, pH 8

0.5 M NaCl

65 C 1.2 108 Studier (1969)

Phage T4 DNA (168.9 kb)~ 16 kb long

fragments

20 mM buffer, pH 7.610 mM KCl

40 mM MgSO4gP32 (in excess over DNA)

37 C 1 108 Alberts and Frey (1970)

Intact Phage DNA

(48.5 kb)

10 mM buffer, pH 5.5

10 mM NaCl

10 mM MgCl2Eco SSB (1.2-fold excess over

DNA)

37 C 1.6 107 Christiansen and Baldwin (1977)

Intact Phage DNA

(48.5 kb)

10 mM buffer, pH 5.2

20 mM NaClEco SSB (10-fold excess over

DNA)2 mM spermine

37 C 3.4 108 Christiansen and Baldwin (1977)

118 bp DNA fragment from

phage X 174

10 mM Tris HCl1 mM EDTA

0.46 mM spermine

25 C 1.4 109 Chaperon and Sikorav (1998)


pSV2gpt

50 mM NaCl

1 mM CTAB

68 C 6 109 Pontius and Berg (1991)

E. coli DNA 0.5 g / ml PERT, 2 M LiSCN 22-24 C 4.2 1010 Kohne et al. 1977


phage X 174

PERT, 0.85 M NaCl 22-24 C 4.2 1010 This work


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Comparison with other systems

involving surface diffusion processes

Role of a reduction of dimensionality in biologicalprocesses: Adam and Delbrck (1968).

Computation of mean time of diffusion (i) to a small targetof diametera within a large diffusion space ofdimensionality iand diameterb: the reduction of

dimensionality can greatly speed up diffusion processes.

Related to a Langmuir-Hinshelwood mechanism! Importance of a liquid-like structure of the interface for

polymer diffusion ( Rouse dynamics (Maier and Rdler,1999) versus solid friction (Guthold et al., 1999)


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Summary on PERT

PERT is an interfacial reaction ssDNA is adsorbed and mobile The rate of PERT is governed by the rate of

vortexing and exceeds a three-dimensional diffusion-

controlled rate.

Use of a heterogeneous reaction medium


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Summary on cyclization and

renaturation experiments (1)

Standard conditions for the study of DNA correspondto homogeneous conditions (actually dilute aqueoussolutions).

In these conditions DNA-DNA interactions arerepulsive (for dsDNA or for similar ssDNA).

The kinetics are slow. The effective concentrations are low One cannot explain the cyclization ofDNA invivo.


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Summary on cyclization and

renaturation experiments (2) In these heterogeneous systems, there is a coupling of thereaction to a phase change:

Collapse; isotropic-liquid crystalline; aggregation (withcondensing agents).

Adsorption at a liquid-liquid interface in PERT

Condensed states of nucleic acids as in vivo; rates ofcyclization compatible with in vivo rates.

Fast kinetics + high effective concentration + low

activation energies: in common with catalysts. Relevant forthe study of the origin of life and for applied biochemistry

(improving hybridization techniques).


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General concepts

Merits and limitations of homogeneous biochemistry. Economics of heterogeneity


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Limitations of homogeneous

or solution biochemistry

The interior of a cell or a virus cannot bedescribed using the concepts of a bulk

homogeneous aqueous solutions:1) Numerous constituents do not mix with one another

(hydrophobic effect; phase separation of thenucleoid from the bacterial cytoplasm).

2) A bulk system is unbounded, in contrast with cellsor viruses.


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Limitations of homogeneous

or solution biochemistry

It excludes the physiology of gaseous

compounds (including respiration), membrane

biology.It excludes the study of biological solid states

(e.g. gels, biomineralization, spores (anhydrobiosis).

It severely limits the study of biologicalmorphology and morphogenesis.


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Homogeneous or solution

biochemistry

- Allows a study of the structure and of the

dynamics of individual biomolecules, in an highly

artificial environment.

- Allows mostly the study of specific interactions

between biomolecules.


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Intermolecular forces in

physics and in biochemistryIn (statistical) physics the focus is often on generic

interactions such as attraction/repulsion, interactions

between like objects or between incompatible ones.

In biochemistry the focus is on specific interactionsbased complementary recognition (Pauling): lock and

key of Fischer (enzymes), ligand (drug)-receptor

magic bullet of Ehrlich, antigen-antibody, base-pairing in nucleic acids.


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Many bodies interactions in

Physics/Biochemistry Interactions between

like structures

Role of repulsive stericeffects/entropic forces:depletion, confinement

Universality

Interactions betweencomplementary

structures Role of attractive forces

Specificity


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Beyond homogeneous

biochemistry: the importance

liquid crystals and surfaces


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States of matter:

4) Mesomorphous states (Friedel) or

Liquid crystalsAn intermediate state of matter between liquid and solidstates. It often involves strongly elongated (anisotropic)molecules: either small organic molecules (for instanceamphiphilic compounds that constitute biological

membranes) or long rods (synthetic polypeptides, DNA,viruses).

Ordering through an anisotropic attraction (Maier andSaupe 1958)

Ordering through steric repulsion only for long rods orsemi-flexible polymers (Onsager 1949, Flory 1956, Khokhlovand Semenov 1982).


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Biological

importance of liquid crystals

Liquid crystals possess internal structures lacking in

liquids, and directional properties not found in gelsThe oriented molecules in liquid crystals furnish in ideal

medium for catalytic action, particularly of the complex

type needed to account for growth and reproduction.

J. D. Bernal Trans. Farad. Soc. (1933) vol. 29, p. 1082.

Examples: membrane enzymology; cyclization and

renaturation of condensed DNA.


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The importance of surfaces

and interfaces in vivo

The compartmentalized organisation of the cell (nucleus,cytoplasm) involves the presence of boundaries(interfaces).

A particular biochemical process often occurs at aspecific location and its product crosses the interfacebetween two compartments.

More than half of the proteins present in the cell areassociated with membranes


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Surface science of DNA:

Douarche et al (2008)


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Economics of heterogeneity

(1)

Increasing the yield or the rate of a reaction through

a decrease of the solubility of the reactant(s):

1) vant Hoff and the

vant Hoff-Dimroth relation

2) Smoluchowskis theory of diffusion-controlledreaction/aggregation


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Economics of heterogeneity (2)

3) The continuous transfer of the product of a reactionto a different phase can be used to displace achemical equilibrium (a common practice in chemicalengineering).

4) The reduction of dimensionality of the reactivesystem can be used to speed up diffusion processes:connection between the Langmuir-Hinshelwoodmechanism and the work of Adam and Delbrck.


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Conclusions (1)

1) History of homogeneous and heterogeneous biochemistry: acomplex story, spanning over 100 years and involving physics

(phase equilibria and phase changes), chemistry and

biochemistry.

2) Todays enzymology and biochemistry are mostly focused onhomogeneous systems, especially for nucleic acids


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Conclusions (2)

The need for a heterogeneous biochemistry:

1) It is necessary to develop experimentally heterogeneoussystems in vitro to model living organisms.

2) It is necessary to take into account both macroscopic andmicroscopic heterogeneity to describe living organisms

3) Heterogeneous systems can be used to improve theefficiency of some reactions (renaturation and cyclization).

4) To permit a unification of the points of view of physicists

(van der Waals, Landau, Wilson) and of biochemists(Fischer, Ehrlich, Pauling).

Physical Chemistry of Natural Selection

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