Urry D.W. (Ed.) What Sustains Life? : Consilient Mechanisms for Protein-Based Machines and Materials

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E.5 Extraordinary Biomaterials Opportunities Arise

565

famed selectivity of enzymes coupled with the

sensitivity to detect a single molecular event.

The latter combines fundamental elements of

the atomic force microscope with the principles

arising out of the hydrophobic and elastic con-

silient mechanisms.

E.5.3J Sound Absorption for Civilian

and Naval Applications

To the best of my knowledge, the data in Figure

7A of Appendix 1^ show 20 Mrad y-

irradiation cross-linked (GVGIP)26o to exhibit

the most extraordinary acoustic absorption yet

observed. This result is corroborated by the loss

shear modulus and loss permittivity data of

Figure 9.15, which in addition shows that the

absorption intensity in the acoustic range

would become twice again as large at body tem-

perature. By varying the hydrophobicity, the

onset temperature may be placed as required

for the application, and the full absorption

capacity develops about 20°C above the onset

temperature. On appropriately increasing the

hydrophobicity of the elastic protein-based

polymer, the acoustic absorption capacity of the

polymer could reach a maximum at a lower

temperature, for example, 10°C (41°F), and

maintain that intensity up to 60°C (140°F).

Accordingly, as noted in Chapter 9, section

9.2.1.4, one designs the protein-based polymer

required for the specific application.

E.5.3.2 Biosensors: Nanomachines

and Nanosensors

E.5.3.2.1 Components of a

Bioelastic Nanosensor

Two basic components comprise the nano-

sensor of interest here: (1) the atomic force

microscope (AFM) designed to measure force

as a function of extension or further modified

to assess frequency dependence of loss shear

modulus under isometric conditions and (2) the

sensing element of elastic protein-based

polymer containing a site or sites of interaction

wherein the interaction changes the state of

hydrophobic association by means of the

apolar-polar repulsive free energy of hydra-

tion, AGap.

E.5.3.2.2 Phosphorylation/Dephosphorylation,

a Most Effective, Selective, and Useful

Change to Detect

Of the many polar functional groups of biology,

phosphate is the chemical group that emanates

the largest apolar-polar repulsion, AGap, that

is,

it is the most effective group for disruption

of hydrophobic association. In particular, the

binding of a single phosphate can disrupt the

hydrophobic association holding part or all of a

globular protein together.

Enzymes, called kinases, phosphorylate the

-OH function of a serine (Ser, S), threonine

(Thr,T) or tyrosine (Tyr, Y) residue that resides

in a specific protein sequence. A specific protein

kinase phosphorylates a specific sequence. The

cardiac cychc AMP-dependent protein kinase

selectively phosphorylates the underscored

serine, S, residue of the sequence RGYSLG,

and protein tyrosine kinase (PTK) selectively

phosphorylates the internal underscored tyro-

sine,

Y, residue in the sequence GIYWHHY

and is specific for that sequence. In cancerous

and other diseased states, the abnormal activi-

ties of kinases can be diagnostic of a number of

diseased conditions (e.g., cancerous tumors and

Alzheimer's disease).

E.5.3.2.3 An AFM Force-extension Design

of a Bioelastic Nanosensor for

Kinase Assays

When a single chain of an elastic protein-based

polymer is strung between AFM cantilever tip

and substrate, a simple monotonic force-exten-

sion curve is obtained."^ On the other hand,

when the single chain comprises a series of glob-

ular protein elements strung between cantilever

tip and substrate, a sawtooth pattern is obtained

with a tooth for every globular element. Thus

our fundamental sensing element becomes a

single globular protein component inserted

between two elastic protein-based polymer

sequences. The force-extension profile for this

construct exhibits a single tooth, as in Figure

9.55A. The globular protein component is

designed with a kinase site, such that phospho-

rylation alters or obliterates the single tooth in

the force-extension profile. Thus, the result is

the detection of a single molecular interaction.

566

Epilogue

Developing a statistical treatment of a set of

such curves provides a measure of the kinase

activity. A series of globular sensing compo-

nents in the single chain would facilitate the

required statistical treatment for relative activ-

ity determination. A set of kinase selective

sensing elements for a number of different

kinases would allow evaluation of the relative

kinase activities in a simple biopsy.

E.5.3.2.4 An AFM Isometric, Loss Shear

Modulus Design of a Bioelastic Nanosensor

for Kinase Assays

A limitation in the AFM force-extension design

of a bioelastic nanosensor for kinase assays is

that it requires a special vibration free mount

for the AFM apparatus because of the need to

minimize the noise in the force-extension curve

in order to detect the small force values. A

design that did not measure force versus exten-

sion, but rather were carried out at fixed exten-

sion, that is, isometrically, would be more

deployable into the field for detection use.

Vlado Hlady (private communication) has

made such a design wherein vibration of the

cantilever and analysis of the damping of the

vibration as a function of frequencies below

the input frequency would be expected to

produce an acoustic absorption spectrum not

unUke that in Figure 9.55B. In this case, in order

to have a suitable loss shear modulus detected

by cantilever vibration at a modest fixed exten-

sion, the chain of a triple-stranded twisted fila-

ment state of the elastic protein-based polymer

would be used as depicted in Figure 9.57. In one

extension setting of the sensing filament, the

acoustic absorption (loss shear modulus),

would be expected to decrease on phosphory-

lation as the unfolding of the globular protein

would effectively open the bridge between can-

tilever tip and substrate, as suggested in Figure

9.55B.

E.5.3.2.5 Approach to Field Detection of

Terrorist Chemical and Biological Agents

Potential for Detection of Single Molecules of

Toxins, Nerve Gas, Explosives, TNT, and DNT

In this case the globular component would be

developed with the specificity, for which pro-

teins are renowned, for interaction with the

molecular species to be detected. For example,

the globular component could derive from the

antibody to the toxin or to the antigen of a par-

ticular organism. The globular sensing compo-

nent could also be a protein with a site for

specific binding of the nerve gas or explosive.

The intent of this section on using biology's

own mechanisms and materials in the design

of nanosensors is to provide a ghmpse of the

potential that Ues in the future for the ultimate

in sensitivity, selectivity, and diversity for detec-

tion of important analytes.

E.6 Living Organisms Create

Order Out of Chaos, But by

What Process?

E.6.1 A Personal Journey of

Enlightenment and Enchantment

The author's personal journey of enlighten-

ment and enchantment began with the inverse

temperature transition exhibited by repeating

sequences of the mammalian elastic fiber. It

began with an inverse phase transition to

greater order of a protein-based machine in

water on raising the temperature rather than

the usual transition to decreased order on

increasing temperature, as in the melting and

vaporization transitions of water. The journey

was buoyed by demonstration that this unique

phase transition could be utilized to intercon-

vert those energies interconverted by living

organisms. Unmodified, the initial sequence is

capable of thermo-mechanical transduction. By

the replacement of as few as 1 amino acid

residue in a sequence of 50 residues or even in

a sequence of 100 residues, a new energy

source, such as chemical energy, could be

accessed. Significantly, the chosen model

protein sequence exhibits the fundamental ele-

ments required for efficient function of protein-

based machines; these are near-ideal elasticity

and hydrophobic association. Hydrophobic

association is, of course, the hallmark of the

inverse temperature transition.

The phenomena exhibited by the designed

elastic-contractile model proteins were catego-

E.6 Living Organisms Create Order Out of Chaos, But by What Process?

567

rized by a set of five Axioms from the perspec-

tive of using the inverse temperature transition

for energy conversion. The physical properties

of these designed elastic-contractile model pro-

teins v^ere extensively characterized w^ith many

experiments and corresponding data analyses

that ultimately brought us to the hydrophobic

and elastic consilient mechanisms. During the

data analysis, a coherence of phenomena with

the behavior of natural proteins was increas-

ingly evident at levels ranging from the gross

anatomical to the molecular. That coherence of

phenomena provided the impetus for a major

focus of this book, which is the central role of

hydrophobic and elastic consilient mechanisms

in protein-based machines discussed in Chap-

ters 7 and 8 and as briefly reviewed above in

section E.4.

E.6.2 A Concluding Contrast of

Means of Achieving Order Out

of Chaos

This Epilogue began with the thesis that

biology's "vital force" arises from coupled

hydrophobic and elastic consilient mechanisms.

In pursuing this thesis, we initially considered

the profound perspectives of renowned physi-

cist and founder of the wave mechanics formu-

lation of quantum mechanics, E. Schrodinger, as

put forward in his memorable book. What is

Life? Now, in completing the thesis of this

Epilogue, which centers on the role of inverse

temperature transitions in biology, we consider

the influential insights of Ilya Prigogine, who

relates the ordering process of biology to his

renowned work on nonequilibrium thermody-

namics, under which conditions more-ordered

systems arise spontaneously from less-ordered

systems.

The purpose here is to contrast the author's

perspective of the dogged manner in which

living organisms create relatively long-lived

order out of chaos from the relatively more

spontaneous transient creations of order arising

out of the Prigogine focus on nonequilibrium

thermodynamics. This brings us to considera-

tion of the arrow of time and of evolution and

natural selection.

E.6.3 Point and Counterpoint of Two

Diametrically Opposed Approaches to

Order Out of Chaos

Point: A highly energized disordered state, far-

from-equilibrium, spontaneously gives rise to

order (spontaneous and relatively unstable)

Counterpoint: Order by the sum of thousands

of small reversible-made-irreversible energy

steps: a protracted step-by-step process to reach

a condition describable as remarkably struc-

tured (non-spontaneous and relatively stable)

Point 1: In emphasizing the relevance of far-

from-equilibrium conditions to biology, Pri-

gogine and Stengers^"^ state, "We can speak of

a new coherence, of a mechanism of 'com-

munication' among molecules. But this type

of communication can arise only in far-from-

equilibrium conditions. It is quite interesting

that such communication seems to be the rule

in the world of biology. It may in fact be taken

as the very basis of the definition of a biologi-

cal system."

In introducing the sense of dissipative struc-

tures,

Prigogine and Stengers^^ state, "In far-

from-equilibrium conditions we may have

transformation from disorder, from thermal

chaos,

into order. New dynamic states of matter

may originate, states that reflect the interaction

of a given system with its surroundings. We have

called these new structures dissipative struc-

tures to emphasize the constructive role of dis-

sipative processes in their formation."

Counterpoint 1: As considered in detail in

Chapter 4, in the biosynthesis of biology's great

macromolecules, proteins and nucleic acids

(DNA and RNA), each residue or base addition

occurs by a reversible reaction in which the equi-

librium constant is essentially one, but with a

pyrophosphate reaction side product. On enzy-

matic breakdown of the pyrophosphate to two

molecules of phosphate by the ubiquitous

enzyme, pyrophosphatase, the reaction becomes

irreversible at the expense of an additional

8kcal/mole. Thus, in the process of construction

of a long chain molecule, living organisms

extravagantly expend energy in "irreversibly"

creating their macromolecular structures that

contain hundreds and even thousands of amino

acid residues or bases in a single chain.

568

Epilogue

Because of the large amount of energy con-

sumed in its construction, a protein, for

example, may reasonably be considered a dissi-

pative structure. However, a single protein chain

is not created in a singular momentary transi-

tion involving a large amount of energy.

Instead, a single protein chain comes into being

step by step, adding one residue at a time, by

utilizing energy in hundreds and even thou-

sands of steps of individual small 8kcal bits.

Once formed the protein can remain intact for

centuries. Even an organism, composed of tens

of thousands of chain macromolecules, can

remain dormant as seeds or spores for centuries

only to spring to life on addition of thermal

and/or chemical energy such as the chemical

water and/or an increase in temperature.

ThuSy

biology produces its great macromole-

cules by means of an energetically extravagant^

step'by-stepy methodical march out of chaos.

Point 2: "On the other hand, far from equi-

Ubrium there appears a variety of mechanisms

corresponding to the possibihty of occurrence

of various types of dissipative structures. For

example, far from equilibrium we ... may also

have processes of self-organization leading to

nonhomogeneous structures to nonequilibrium

crystals."^'

Counterpoint

In fact, living organisms com-

monly create pairs of complementary protein

structures that, when separately dissolved in

solution, do not show the usual thermal or

motional signs of being energized. Instead the

protein structures can exhibit restricted

freedom of motion due to repulsions between

groups constrained to coexist by sequence.

However, they are nonetheless energized by

an intramolecular apolar-polar repulsion, the

AGap, between the hydrophobic and charged

residues constrained to coexist by sequence. On

combining the solutions of complementary,

sequence-energized chains, the complementary

proteins communicate; they spontaneously and

stoichiometrically associate into ordered,

stable, and homogeneous structures at equilib-

rium. This can occur spontaneously on mixing

when above Tt for the mixture, or it can occur

on raising the lowered temperature when below

Tt for the mixture. The latter occurs with the

uptake (or assimilation) of heat energy into the

system, not with its dissipation or dissimilation.

Communication among molecules may arise

in biology from the complementarity of struc-

tures,

as demonstrated with the designed E/nF

and K/nF series of protein-based polymers.

These structures are defined in Table 6.1 and

characterized in Figures 6.3 and 6.4. Communi-

cation between designed molecules results

from a lowering of the free energy on alignment

due to a decrease of the AGap that resides within

each separate molecule. In practice, this trans-

lates into the capacity to design highly entropic

elastic fibers of protein-based polymers with an

increase of one to two orders of magnitude in

elastic moduli and break stresses and with

improved break strains of 300%. The repulsive

AGap within each complementary chain mole-

cule becomes relieved on alignment by means

of ion pairing of negative carboxylate with

positive amino side chains that recur with the

same periodicity. More regular cross-linking

results in the improved materials properties

(see Chapter 9, section

9.4.3.1,

and Figure 9.20).

This biology-based, actually hydrophobic

consilient mechanism-based, communication

between molecules leads to self-organization

into homogeneous structures at equilibrium

rather than "to nonhomogeneous structures to

nonequilibrium crystals." Thus, it seems to your

author that living organisms create order out of

chaos by a process distinct from that arising out

of the Progogine analyses of nonequilibrium

thermodynamics. Expanding our understanding

of biology's creation of ordered macromole-

cules out of the chaos of mixtures of amino acids

and of bases provides insight into just how

biology reverses the universal arrow of time.

This aspect that leads to evolution and natural

selection was treated in Chapter 6 and is

abstracted in what follows.

E.7 Evolution by Inverse Temperature Transition Reverses The Otherwise Universal Arrow of Time 569

E.7 Evolution by Inverse

Temperature Transition Reverses

The Otherwise Universal Arrow

of Time

E.7.1 Biology's Exception to the

"Times Arrow" for the Universe

EJ.IJ Eddington

Introduction of the

Concept of ''Times Arrow"

Eddington^^ underscores his high regard for the

second law of thermodynamics in his view that

"The law that entropy always increases—the

second law of thermodynamics—holds, I think,

the supreme position among the laws of

Nature." As an increase in entropy measures

the increase in disorder, that is, the increase

in randomness, Eddington^^ developed the

concept of "times arrow," with the following

thought:

Let us draw an arrow arbitrarily. If as we follow the

arrow

find

more and more of the random element

in the state of the world, then the arrow is pointing

towards the future; if the random element decreases

the arrow points toward the past. That is the only

distinction known to physics. I shall use the phrase

"times arrow" to express this one-way property of

time which has no analogue in space. It is a singu-

larly interesting property from a philosophical

standpoint.

In short, as time progresses the universe

becomes more disordered.

Thus,

we have the dilemma that the arrow of

time for the universe points toward increasing

disorder and uniformity, whereas the arrow of

time for biology points toward greater order

and diversity.

E.7,1.2 An Elegant Statement of the

Dilemma by Toffter in the Foreword to

Prigogine and Stengers' Book

Imagine the problems introduced by Darwin and his

followers! For evolution, far from pointing toward

reduced organization and diversity, points in the

opposite direction. Evolution proceeds from simple

to complex, from "lower" to "higher" forms of Life,

from undifferentiated to differentiated structures.

And, from a human point of view, all is quite opti-

mistic. The (biological) universe gets "better" orga-

nized as it ages, continually advancing to a higher

level as time sweeps by.^^

How can this be? We addressed this to some

extent when considering the process whereby

living organisms create order out of chaos.

However, biology's reversal of the arrow of

time derives from yet deeper roots.

E.7.2 Evolution by Inverse

Temperature Transition Achieves

Biology's Reversal of the Universal

Arrow of Time

Biology's reversal of the much-noted arrow of

time and equivalently biological evolution

derive simply from fundamental reality of

biosynthesis within the context of inverse

temperature transitions as expressed in the

hydrophobic consilient mechanism. The pro-

duction of a new and improved protein-based

machine occurs by chance, but most signifi-

cantly it occurs at a cost in energy no greater

than that required to produce the initial less

useful protein-based machine. This is the nature

of the biosynthesis of protein and of the other

great macromolecules (the nucleic acids, DNA

and RNA) of biology.

Remarkably, for protein-based machines that

function by means of the hydrophobic con-

silient mechanism, the structure of the genetic

code is such that a single base mutation can

produce a protein-based machine capable of

accessing a new energy source, and another

single base mutation can produce a more effi-

cient protein-based machine. This has been

experimentally demonstrated by the design of

elastic contractile model proteins that access

new sources of energy. For example, the change

of a single Val residue to a glutamic acid residue

in a 100 residue sequence (possible by a single

base change of thymine to adenine) can add the

capacity of chemo-mechanical transduction to

the model protein known for thermo-mechani-

cal transduction (see Chapter 6).

570

Epilogue

E.7.2.1 The Genetic Code's Bias for Use

by the Inverse Temperature Transition

The fundamental residues of the inverse tem-

perature transition are hydrophobic, and there

is a unique family of the genetic code that is

entirely hydrophobic. As shown in Table 6.2, the

hydrophobic family is the one with U as the

second base of the triplet codon, namely, XUY.

Any of the four bases of RNA—A (adenine),

U (uracil), G (guanine), and C (cytidine)—can

be in positions 1 and 3 of the triplet code, but

U is always found as the second base of the

codon for the hydrophobic family. A change in

position 1 and position 3 simply allows selec-

tion of one member of the hydrophobic family

from another. Position 3 in the cases of Leu

(CUY) and Val (GUY) gives redundancy, that

is,

four different codons encode for Leu as do

four different codons encode for

Val.

Therefore,

it is said that both Val and Leu have a redun-

dancy of four. For the Leu and Val residues, a

change in the base in position 3 does not change

the amino acid residue.

EJ.2.2 The Most Fundamental Step of

Evolution-Natural Selection Is to Access a

New Energy Source at No Additional Cost

in Energy by the Biased Genetic Code

Importantly for the evolution of protein-based

machines, a single base change in position 2 of

the four codons for Val accesses the very impor-

tant negatively charged amino acids, and a

single base change in two of the codons for Leu

access the also important positively charged

Lys residue. The introduction of a single

charged amino acid residue accesses chemical

energy inputs for chemo-mechanical transduc-

tion, and if one allows for ion pairing to redox

groups, it also allows for electrical energy

input for electro-chemical transduction. A

single base change converts the fundamental

thermo-mechanical transduction of the inverse

temperature transition to chemo-mechanical

transduction and also to electro-mechanical

transduction.

As discussed regarding biosynthesis in

Chapter 4, the cost in energy, in moles of ATP,

to produce a protein of a given length is the

same regardless of composition. Therefore, the

single base mutation required to access chemi-

cal energy occurs at no additional cost to the

organism. In the process of natural selection,

therefore, the organism that can access a new

energy source will more effectively compete

and will survive under conditions of stress

whereas the less capable organism will not.

When protein-based machines function by the

hydrophobic consilient mechanism, the structure

of the genetic code is ideally suited for the evo-

lution of protein-based machines to access new

forms of energy.

E.7.2.3 A Refinement Step of

Evolution-Natural Selection: To Produce

a More Efficient Protein-based

Machine at No Extra Cost Using the

Biased Genetic Code

As discussed in Chapter 5 and specifically con-

sidered in Chapter 6 in relation to evolution, the

replacement of a Val residue by a phenylalanine

(Phe,

F) residue results in a more efficient

protein-based machine for chemo-mechanical

transduction or for electro-mechanical trans-

duction (see Figures 5.20,5.34, and 5.36 and the

associated discussions in Chapter

5).

The muta-

tion from Val to Phe occurs with a single base

change at the DNA level of guanine to thymine.

As listed in Table 6.2, a single base change in

position 1 can access a more hydrophobic

residue, as in Val to Phe, to provide a more effi-

cient protein-based machine.

Again, as discussed regarding protein syn-

thesis in Chapter 4, the cost in energy, in moles

of ATP, to produce a protein of a given length

is the same regardless of composition. There-

fore,

the single base mutation required to

produce a more efficient protein-based

machine occurs at no additional cost to the

organism. By means of natural selection, there-

fore,

the organism with the more efficient

machine will compete more effectively and will

survive under conditions of stress, whereas the

less capable organism will not.

When protein-based machines function by the

hydrophobic consilient mechanism, the genetic

code is ideally suited for their evolution toward

new machines with greater efficiency.

References

571

Thus, from the perspective of the inverse

temperature transition, evolution and natural

selection become apparent consequences for

protein-based machines that function by the

hydrophobic and elastic consilient mechanisms.

E.8 Maintaining the Admonition

of Bacon

This volume represents a sincere attempt,

backed by extensive commitment and effort,

to overcome some of the current "idols which

beset men's minds" in the area of protein-based

machines and materials. More broadly, it opens

the door for a new look at the physical basis

whereby amphiphiUc polymers function in

water and presents the basis with which to engi-

neer protein-based polymers as has not previ-

ously been possible. The primary purpose is to

extend knowledge of the forces that provide

function for protein-based machines and mate-

rials and thereby to achieve a greater compre-

hension of living organisms and to develop new

materials for the benefit of society.

We hope that this volume may provide a

milestone in the pathway to greater under-

standing of what sustains Life and a milestone

in the biomaterials renaissance, but that it do so

without itself becoming an idol that stands as a

barrier to further progress. Whatever step has

been taken, it should be viewed with adherence

to the four-century-old admonition of Sir

Francis Bacon. Thus we end this volume as

Bacon in 1620 began his Preface to The New

Organon or True Directions Concerning the

Interpretation of Nature: "Those who have

taken upon them to lay down the law of nature

as a thing already searched out and understood,

whether they have spoken in simple assurance

or professional affectation, have therein done

philosophy and the sciences great injury. For as

they have been successful in inducing

belief,

they have been effective in quenching and stop-

ping inquiry; and have done more harm by

spoiling and putting an end to other men's

efforts than good by their own."*

References

By definition in Webster's Dictionary, vital is

"concerned with or necessary for the mainte-

nance of life" and "performing an essential role

in the living body." As given in the Britannica

2002,

the sense of elan

vital,

"the vital force or

impulse of life," is a creative principle of Henri

Bergson "immanent in all organisms and respon-

sible for evolution."

E.O. Wilson,

Consilience:

The Unity of Knowl-

edge.

Alfred E.

Knopf,

New York, 1998,

D.W. Urry and T.M. Parker, "Mechanics of

Elastin: Molecular Mechanism of Biological

Elasticity and its Relevance to Contraction." /.

Muscle

Res.

Cell

Motil,

23,

541-547, 2002.

D.W.

Urry,T. Hugel,

Seitz,

Gaub,

Sheiba,

J. Dea, J. Xu, and T. Parker, "Elastin: A Repre-

sentative Ideal Protein Elastomer."

Philos.

Trans.

Soc.

Lond.,

B 357,169-184,2002.

D.W.

Urry,T. Hugel,

Seitz,

Gaub,

Sheiba,

J. Dea, J. Xu, L. Hayes, F. Prochazka, and T.

Parker, "Ideal Protein Elasticity: The Elastin

Model." In ''Elastomeric Proteins: Structures,

Biomechanical

Properties

and

Biological

Roles''

PR. Shewry, A.S. Tatham, and A.J. Bailey, Eds.,

Cambridge University

Press,

The Royal Society;

Chapter Four, pages 54-93,2003.

With the remarkable progress that has been made

in the descriptive understanding of biology and

biology's great macromolecules and of polymers in

general, this admonition of four centuries ago may

seem unwarranted. Nor should the reprove be laid at

the feet of the grand pioneers of molecular mechan-

ics and molecular dynamics computations such as

Harold Scheraga, Martin Karplus, Peter Kollman,

Micheal Levitt, Paul Flory, and Henry Eyring,

for they have taken up the ultimate challenge and

hewn the path toward that definitive goal. They

warrant high praise and gratitude for advancing and

providing their methodologies. Yet wanting in all

cases,

for example, remains the proper treatment of

the "waters of Thales."

In our view, it is those who use yet-incomplete

theoretical treatments and from this stage dictate

absolute conclusions, even though deficient when

compared with experimental data, who remain

capable of the injury of which Bacon

wrote.

noted

earlier in this Epilogue, the recognition of present

impediments arising from interpretations of such

practitioners is repeated

here:

Useful approximations

the

past become

"idols"

in the present that

stand as

barriers

the

future.

572

Epilogue

6. Z.R. Wasserman and F.R. Salemme, "A Molecu-

lar Dynamics Investigation of the Elastomeric

Restoring Force in Elastin." Biopolymers, 29,

1613-1631,1990.

E. Schrodinger, What is Life?: The Physical

Aspect of the Living Cell with Mind and Matter

and Autobiographical Sketches. Cambridge Uni-

versity Press, 1944 (1967 edition, p. 68).

8. I. Prigogine and I. Stengers, Order Out of Chaos:

Man's New Dialogue with Nature. Bantam Book,

New York, 1984, p. 103.

9. K. Kinosita, R. Yasuda and H. Noji, "Fi-ATPase:

A Highly Efficient Rotary ATP Machine."

Essays Biochem. Mol Motors, 35, 3-18, 2000.

10.

The capacity to have any 1 of 20 different amino

acid residues at each position in a protein

sequence with physicochemical properties span-

ning from very oil-like to vinegar-like, as demon-

strated in Figure 2.1, and the simultaneous

capacity to retain complete integrity with respect

to molecular asymmetry (see Chapter 3, section

3.1.6 and Figure 3.3) combine to result in the

remarkable capabiUties of protein sequences.

Lest one gets lost in the sense of improbability

of such sequences, however, their biosynthesis

requires such an extraordinary amount of energy

in total number of ATP molecules consumed for

the addition of each amino acid residue that

their construction is more aptly described as bla-

tantly extravagant. This constitutes the central

message of Chapter 4.

11.

E. Schrodinger, What is Life?: The Physical

Aspect of the Living Cell with Mind and Matter

and Autobiographical Sketches. Cambridge

University Press, 1944, (1967 edition, p. 76).

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Appendix 1

Mechanics of Elastin: Molecular

Mechanism of Biological Elasticity and

Its Relationship to Contraction

Dan

URRY^

2 *

and Timothy M. PARKER^

Abstract

Description of the mechanics of elastin requires

the understanding of two interUnked but dis-

tinct physical processes: the development of

entropic elastic force and the occurrence of

hydrophobic association. Elementary statisti-

cal-mechanical analysis of AFM single-chain

force-extension data of elastin model mole-

cules identifies damping of internal chain

dynamics on extension as a fundamental source

of entropic elastic force and eliminates the

requirement of random chain networks. For

elastin and its models, this simple analysis is

substantiated experimentally by the observa-

tion of mechanical resonances in the dielectric

relaxation and acoustic absorption spectra, and

theoretically by the dependence of entropy on

frequency of torsion-angle oscillations, and by

classical molecular-mechanics and dynamics

calculations of relaxed and extended states of

the p-spiral description of the elastin repeat,

(GVGVP)„. The role of hydrophobic hydration

in the mechanics of elastin becomes apparent

under conditions of isometric contraction.

Reprinted from

Journal

Muscle Research

and

Cell

Motility,

23,543-559,2002.

Kluwer Academic

Publishers.

^University of Minnesota, Twin Cities Campus,

BioTechnology Institute, 1479 Gortner Avenue, St.

Paul, MN 55108-6106; ^Bioelastics Research Ltd.,

2800 Milan Court, Suite 386, Birmingham, AL,

35211-6918, USA

*To whom correspondence should be addressed:

E-mail: durry98@aol.com

During force development at constant length,

increase in entropic elastic force resulting from

decrease in elastomer entropy occurs under

conditions of increase in solvent entropy. This

eliminates the solvent entropy change as the

entropy change that gives rise to entropic

elastic force and couples association of hydro-

phobic domains to the process. Therefore, asso-

ciation of hydrophobic domains within the

elastomer at fixed length stretches intercon-

necting dynamic chain segments and causes an

increase in the entropic elastic force due to the

resulting damping of internal chain dynamics.

Fundamental to the mechanics of elastin is the

inverse temperature transition of hydropho-

bic association that occurs with development of

mechanical resonances within fibrous elastin

and polymers of repeat elastin sequences,

which, with design of truly minimal changes in

sequence, demonstrate energy conversions

extant in biology and demonstrate the special

capacity of bound phosphates to raise the free

energy of hydrophobic association.

Introduction

As a brief introduction to the mechanics of

elastin, noted are the composition and seq-

uence of bovine elastin, the inverse phase tran-

sition behavior of the elastin and related

protein components, and the conformational

aspects of the most representative repeating

sequence of elastin.

574