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ARTICLE IN PRESS

Nonlinear Analysis ( ) –

www.elsevier.com/locate/na

1

Nonlinear assembly kinetics and mechanical

properties of biopolymers 3

Jack Tuszy´ nski

a,∗,1

, Stéphanie Portet

b,2

, John Dixon

c

a

Department of Physics, University of Alberta, Edmonton, Alberta, Canada T6G 2J1 5

b

The Samuel Lunenfeld Research Institute,Room 1060, Mount Sinai Hospital, 600 University Avenue,

Toronto, Ontario, Canada M5G 1X5 7

c

Department of Physics, University of Warwick, Coventry CV4 7AL, UK

Abstract

9

This paper discusses the role of nonlinearities in the physical description of key biomolecules that

participate in crucial subcellular processes, namely actin, microtubules and ions crowding around 11

these ﬁlaments. The assembly kinetics of actin is that of a nonlinear process that is governed by

coupled nonlinear equations involving monomer concentration and ﬁlament number as the dynamical 13

variables. The dendritic growth of actin networks in cell motility phenomena is described by the

coupling of actin ﬁlaments to the protein Arp2/3. We then discuss how coupled differential equations 15

describing the interactions between ions in solution and the ﬁlament they surround can lead to solitonic

signal transmission. We also investigate the role of nonlinear dynamics in the formation of micro- 17

tubules. Space-ﬂight laboratory experiments have shown that the self-organization of microtubules

is sensitive to gravitational conditions. We propose a model of self-organization of microtubules in 19

a gravitational ﬁeld based on the dominant chemical kinetics. The pattern formation of microtubule

concentration is obtained in terms of a moving kink. Finally, we present a model of elastic proper- 21

ties of microtubules describing a microtubule as an elastic rod. We found that when the microtubule

is subjected to bending forces, the tangent angle satisﬁes a Sine-Gordon equation whose solutions 23

∗

Corresponding author. Fax: +1 780 492 0714.

E-mail address: jtus@phys.ualberta.ca (J. Tuszy´ nski).

1

This work was supported by grants from MITACS and NSERC awarded to J.A.T.

2

S.P. acknowledges the support of the Bhatia post-doctoral fellowship.

0362-546X/$ - see front matter © 2005 Published by Elsevier Ltd.

doi:10.1016/j.na.2005.01.089

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2 J. Tuszy´ nski et al. / Nonlinear Analysis ( ) –

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describe kink and anti-kink bending modes that may propagate at a range of velocities along the length 1

of the microtubule.

© 2005 Published by Elsevier Ltd. 3

Keywords: ; ;

1. Introduction 5

The cell’s cytoskeleton is composed of three different types of ﬁlaments organized in

networks: microﬁlaments (MFs), intermediate ﬁlaments (IFs) and microtubules (MTs). 7

MFs are a double helix of globular actin subunits. In a lamellipod, the MF network appears

as a 3D gel which is involved in cell motility. The 2D arrangement of MFs in contractile 9

ﬁbers appears to formcable-like structures involved in the maintenance of the cell shape and

transduction pathways. The polymerization dynamics and ﬁlament organization of actin has 11

been modeled by Edelstein-Keshet et al. [6,9]. In the conﬁguration of parallel strands, MFs

often formthe core of microvilli, while in an anti-parallel arrangement, actin in conjunction 13

with myosin brings about muscle contraction in the presence of ATP. MFs are often found

with the lattice conﬁguration near the leading edge of growing or motile cells where they 15

provide greater stability to the newly formed region. New actin ﬁlaments are nucleated at

the leading edge of the cell’s growth and trailing MFs are disassembled [2,3]. 17

MTs are long, hollow cylindrical objects made up of typically 13 longitudinal protoﬁla-

ments consisting of -tubulin heterodimers, and are involved in a number of functions of 19

the cell such as cell shape maintenance, mitosis and intracellular transport. By biological

standards, MTs are rigid polymers with a large persistence length of 6 mm. From Janmey’s 21

experiments [14], MTs suffer a larger strain for a small stress compared to either MFs or

IFs. The rupture stress for MTs is very small and typically is about 0.4–0.5 N/m

2

[14]. The 23

ratio of ﬂexural rigidity per unit length to thermal energy in the case of MTs is of the order

of 100, whereas for actin it is only 2, meaning that the MTs are not greatly inﬂuenced by 25

thermal agitation [30].

2. Actin ﬁlaments 27

In this section, we give examples of the strong dependence of actin’s dynamic behaviors

on nonlinearities: two models of actin polymerization and one model of transport induced 29

by nonlinear properties of actin.

2.1. Polymerization dynamics of actin ﬁlaments 31

Polymerization of F-actin from G-actin is a largely monotonic process that is dependent

onATP. F-actin assembles according to a standard nucleation–elongation mechanism. Once 33

assembled, MFs have a diameter of about 8 nm. Oosawa and Asakura [22] established that

spontaneous polymerization of actin monomers requires an unfavorable nucleation step 35

followed by rapid elongation. They also determined that actin ﬁlaments can break and anneal

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J. Tuszy´ nski et al. / Nonlinear Analysis ( ) – 3

end to end. Inclusion of a fragmentation reaction improved the ﬁt of nucleation–elongation 1

mechanisms to the observed time course of polymerization [4,7,29]. Earlier models for actin

polymerization showed that the critical size for the nucleus is somewhere between a dimer 3

and a trimer, and that the number of explicit nucleation steps does not affect the results of

the model [7,11,12,26]. With these considerations in mind, a simple ﬁve-step model was 5

proposed [28]:

A + A

k

+1

k

−1

A

2

k

+1

= 10 M

−1

s

−1

, k

−1

= 10

6

s

−1

, (1)

7

A + A

2

k

+2

k

−2

A

3

k

+2

= 10 M

−1

s

−1

, k

−2

= 10

3

s

−1

, (2)

A + A

3

k

+3

k

−3

A

4

k

+3

= 10 M

−1

s

−1

, k

−3

= 10 s

−1

, (3)

9

A + A

4

k

+4

k

−4

N k

+4

= 10 M

−1

s

−1

, k

−4

= 0 s

−1

, (4)

A + N

k

+

k

−

N k

+

= 10 M

−1

s

−1

, k

−

= 1 s

−1

, (5)

11

where A, A

i

, and N represent the concentrations of actin monomers, ﬁlaments of i actin

monomers, and all longer ﬁlaments, respectively. The rate constants for the last reaction 13

have been experimentally measured [23] and lead to the correct critical concentration

(C

c

>0.1 M), but the other rate constants are only approximations from kinetic simu- 15

lations, chosen to reproduce the time course of polymerization over a limited range of

actin monomer concentrations. Such polymerization curves have already been published 17

[4,7,11,12,26,29]. Filaments longer than 4 subunits are assumed to be stable and the back-

reaction rate k

−4

is set to zero. The coupled ﬁrst-order differential equations that arise from 19

the set of reactions above are ‘stiff-equations’ due to the large differences in the forward

and back reaction rates. This set of equations produces correct polymerization curves, but 21

the average length as a function of actin concentration is completely incorrect. The mean

lengths of the observed ﬁlaments are almost independent of the initial concentration of actin 23

monomers, while this simple model predicts a mean length with quite a different behavior,

especially at high concentrations of actin. To solve this problem, additional processes are 25

added to the model, namely the reaction

N + N

k

a

k

f

N, (6)

27

where k

a

is the annealing rate and k

f

the fragmentation rate of a ﬁlament. Since two ﬁlaments

are joined to form a new ﬁlament, the annealing rate has a quadratic dependence 29

˙

N = k

+

AA

4

− k

a

N

2

+ k

f

N. (7)

It is reasonable to assume that annealing of two ﬁlaments is limited by diffusion, since 31

ﬁlaments diffuse more slowly than monomers. Erickson [10] estimated the fragmentation

rate to be in the neighborhood of k

f

≈ 10

−8

s

−1

. 33

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4 J. Tuszy´ nski et al. / Nonlinear Analysis ( ) –

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The amount of polymerized protein in the system is given by the expression 1

P = A

0

− A − 2A

2

− 3A

3

− 4A

4

, (8)

where A

0

represents the initial actin concentration. The average length of a ﬁlament is given 3

simply by L = P/N and we get

˙

N = k

+

AA

4

− k

a

N

3

L

+ k

f

1

P + k

f

2

P

2

, (9)

5

where all of the constants are absorbed in the variable k

a

. The values for the rate constants

depend on the actin concentration and the ﬁlament density and length. 7

When actin is puriﬁed from cells some actin-associated proteins remain in the sample,

including the capping protein CapZ. A reaction for capping ﬁlaments can be written as 9

CapZ + N

k

z+

k

z−

N

∗

, (10)

where N

∗

represents a ﬁlament that is capped at the barbed end preventing monomer 11

addition or dissociation as well as annealing. The constants for the above reaction are

k

z+

≈ 3.5 M

−1

s

−1

and k

z−

≈ 3 × 10

−4

s

−1

[25]. The total number of ﬁlaments in the 13

system is N + N

∗

and the average length is now given by

L =

P

N + N

∗

. (11)

15

A capped ﬁlament can still fragment, but it can only anneal with an uncapped ﬁlament,

since this requires at least one free barbed end. Since two uncapped ﬁlaments can anneal in 17

two ways, but capped and uncapped ﬁlaments have only one method of annealing, the rate

of annealing is half the original value. 19

2.2. A simpliﬁed model for actin dendritic network aggregation

The nucleation of new F-actin ﬁlaments is a prerequisite for cell shape remodeling and 21

motility processes involving rapid actin polymerization. It can either involve a de novo

nucleation of new ﬁlaments or a catalytic nucleation from pre-existing ﬁlaments. In the 23

de novo nucleation, a trimeric nucleation core initiates a new ﬁlament. New ﬁlaments

resulting from a catalytic nucleation can be initiated either by the fragmentation of pre- 25

existing ﬁlaments or by a branching process requiring the presence of the Arp2/3 protein

complex which is bound to the barbed end or to the side of a mother ﬁlament with the new 27

daughter ﬁlament polymerizing out from it at a 70

◦

angle. The Arp2/3 complex has to be

associated with other molecules as WASP family proteins or cortactin to be active. During 29

these rapid actin polymerization processes, other important mechanisms take place, such

as the capping of the branched ends by, for example, gelsolin, avoiding polymerization 31

at these ends to not exhaust the G-actin pool and to promote polymerization at precisely

localized sites. All these processes induce strong nonlinearities. The events considered in 33

our simpliﬁed model follow.

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2.2.1. De novo nucleation 1

The nucleation core of F-actin is a trimer. This type of nucleation is G-actin dependent.

3G

v

+

v

−

F, (12)

3

where G is a G-actin monomer and F is a free F-actin ﬁlament.

2.2.2. Catalytic nucleation (branching) 5

The Arp2/3 complex is able to form new barbed ends by branching at the ends of existing

ﬁlaments. WASP (and/or cortactin) is required for activation of the Arp2/3 complex: it 7

is a nucleation-promoting factor. This type of nucleation is F-actin dependent. Thus, the

catalytic nucleation involves different events. The ﬁrst step is the activation of the Arp2/3 9

complex,

W + A + G

:

→ Y, (13) 11

where W is a WASP molecule, A is an inactive Arp2/3 complex and Y is an active Arp2/3

complex. The second step of the catalytic nucleation is the branching process 13

F + Y

[

→ 2F

N

+ W or F

N

+ Y

[

→ 2F

N

+ W, (14)

where F

N

represents an F-actin ﬁlament involved in the dendritic network. 15

2.2.3. Polymerization/depolymerization

F + G

¬

+

¬

−

F or F

N

+ G

¬

+

¬

−

F

N

. (15)

17

These equations represent the elongation/disassembly processes of ﬁlaments.

2.2.4. Debranching 19

F

N

o

→ F + A. (16)

The turnover betweenATP G-actin andADP G-actin is assumed to be instantaneous. The 21

sequestration of the soluble pool, the severing and the capping/uncapping of ﬁlaments are

not considered in the model: all these processes involve the action of other types of proteins, 23

for example gelsolin. Thus, the proposed model could describe the self-aggregation of F-

actin ﬁlaments into dendritic networks. The reversible processes of annealing/fragmentation 25

are not considered in our model.

We assume that the inactive Arp2/3 complex concentration, A, and the WASP protein 27

concentration, W, are constant. Thus, our model is composed of 4 state variables (G, Y, F,

and F

N

) and 7 parameters (v

+

, v

−

, :, [, ¬

+

, ¬

−

, and o). 29

˙

G = 3v

−

F

. ,, .

Elimination

− 3v

+

G

3

. ,, .

Nucleation

−¬

+

G(F + F

N

)

. ,, .

Polymerization

+ ¬

−

(F + F

N

)

. ,, .

Depolymerization

− :G

.,,.

Activation

, (17)

˙

Y = :G

.,,.

Activation

−[Y(F + F

N

)

. ,, .

Branching

, (18)

31

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6 J. Tuszy´ nski et al. / Nonlinear Analysis ( ) –

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0

1

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

G

F

F

N

0

1

0

0.1

0.2

0.3

0.4

0.8

0.6

0.4

0.8

0.6

0.4

0.2

0.2

0

0.05

0.1

0.15

0.2

G

F

F

N

Fig. 1. Insensitivity of the actin debranching process to the initial conditions and for various parameter choices

([ = 5, v

+

= 100 left; [ = 0.05, v

+

= 10 right).

˙

F = v

+

G

3

. ,, .

Nucleation

− v

−

F

.,,.

Elimination

+ oF

N

.,,.

Debranching

− [FY

.,,.

Branching

, (19)

1

˙

F

N

= 2[FY

. ,, .

Branching

+ [F

N

Y

. ,, .

Branching

− oF

N

.,,.

Debranching

, (20)

where v

+

is the rate constant of ﬁlament nucleation by trimerization and v

−

is the rate 3

constant of nucleation core elimination. Here ¬

+

and ¬

−

represent the rate constants of

assembly of a G-actin monomer to an F-actin ﬁlament and of disassembly of a G-actin 5

monomer from an F-actin ﬁlament, respectively. Here : is the rate constant for the Arp2/3

complex activation by WASP proteins. [ is the rate constant of the ﬁlament branching, and 7

o is the rate of the dissociation of a ﬁlament from the network, the rate of debranching. All

the rate constants and the initial concentrations are positive. (See Fig. 1 for an illustration 9

of the dynamics of these equations.)

2.3. Actin ﬁlaments as nonlinear ionic LRC transmission lines 11

In this section, we set up an electrical model of the actin ﬁlament using inductive, ca-

pacitive and resistive elements. We apply Kirchhoff’s laws to that section of the effective 13

electrical circuit for one monomer, M, which involves coupling to neighboring monomers.

We expect a potential difference between one end of the monomer generated between the 15

ﬁlament core and the ions lying along the ﬁlament at one Bjerrum length away. Due to

viscosity we also anticipate a resistive component to these currents which we insert in se- 17

ries with L and denote it by R

1

. In parallel to these components, there exists a resistance,

R

2

, acting between the Bjerrum ions and the surface of the ﬁlament. In series with this 19

resistance, we have a capacitance, C

0

. We assume that the charge on this capacitor varies

in a nonlinear way with voltage. Thus for the nth monomer, 21

Q

n

= C

0

(V

n

− bV

2

n

), (21)

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J. Tuszy´ nski et al. / Nonlinear Analysis ( ) – 7

where b is expected to be small. From Kirchhoff’s laws, 1

v

n

− v

n+1

= L

dI

n

dt

+ I

n

R

1

, (22)

where v

n

and v

n+1

are the voltages across neighboring resistors. Similarly, if the voltage 3

across the capacitor is V

n

+ V

0

, where V

0

is the bias voltage of the capacitor,

v

n

= R

2

(I

n−1

− I

n

) + V

0

+ V

n

. (23) 5

Furthermore, the current difference is I

n−1

− I

n

= dQ

n

/dt . Combining and transforming

these equations, we obtain 7

L

d

2

Q

n

dt

2

= V

n+1

+ V

n−1

− 2V

n

− R

1

C

0

d

dt

(V

n

− bV

2

n

)

− R

2

C

0

_

2

d

dt

(V

n

− bV

2

n

) −

d

dt

(V

n+1

− bV

2

n+1

)

−

d

dt

(V

n−1

− bV

2

n−1

)

_

. (24)

A continuum approximation using a Taylor expansion in a small spatial parameter a 9

gives

LC

0

j

2

V

jt

2

= a

2

(j

xx

V)+R

2

C

0

j

jt

(a

2

(j

xx

V))−R

1

C

0

jV

jt

+R

1

C

0

2bV

jV

jt

, (25)

11

which forms the basis of our physical analysis of the ion conduction problem [27].

As a result of applying an input voltage pulse with an amplitude of approximately 200 mV 13

anda durationof 800 s toanactinﬁlament, electrical signals measuredat the opposite endof

the actin ﬁlament reached a peak value of approximately 13 nAand lasted for approximately 15

500 s [17]. In a related earlier experiment [18], the wave patterns observed in electrically

stimulated single actin ﬁlaments were remarkably similar to recorded solitary waveforms 17

from various experimental studies on electrically stimulated nonlinear transmission lines

[16,19,21]. 19

Solutions of Eq. (25) are taken as traveling waves, so the voltage is a function of a

moving coordinate, ¸ = x − v

0

t , where v

0

is the propagation velocity. Eq. (25) then 21

becomes

R

2

a

2

v

0

L

d

3

V

d¸

3

+ (v

2

0

− c

2

0

a

2

)

d

2

V

d ¸

2

+

_

2bR

1

v

0

L

V −

R

1

v

0

L

_

dV

d¸

= 0, (26)

23

where c

2

0

= 1/(LC

0

). Eq. (26) may be integrated once to yield

R

2

a

2

v

0

L

d

2

V

d¸

2

+ (v

2

0

− c

2

0

a

2

)

dV

d¸

+

1

2

_

2bR

1

v

0

L

V −

R

1

v

0

L

_

2

L

2bR

1

v

0

= d

0

, (27)

25

where d

0

is an integration constant.

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To ﬁnd solutions in terms of Jacobi elliptic excitations, we choose the propagation ve- 1

locity, v

0

, so that v

2

0

= c

2

0

a

2

= v

2

max

. For convenience, we deﬁne a shifted voltage by

W = V − 1/(2b) and obtain an analytical solution in the form 3

W = w

3

− (w

3

− w

2

)sn

2

_

_

3a

2

R

2

(w

3

− w

1

)

2

√

2bR

1

(¸ − ¸

0

), k

_

, (28)

where 0k 1 with k =

√

(w

3

− w

2

)/(w

3

− w

1

) where k is the elliptic modulus. When 5

k → 0 the sn(·) function tends to the trigonometric sine function. Simultaneously, the

amplitude of the wave vanishes and so does the wavelength. On the other hand, when 7

k → 1 we obtain

W = w

1

+

2(w

2

− w

1

)

1 + cosh(

√

w

2

− w

1

(¸ − ¸

0

))

. (29)

9

This solution represents a localized bump propagating with velocity v

0

. The waves in Eq.

(28) and the solitary wave in Eq. (29) travel at the velocity v

0

estimated as v

max

=3×10

5

m/s, 11

which is astonishingly high indicating a purely electromagnetic resonant energy transfer

from one LC element to the neighbor with no loss. 13

The voltage equation, Eq. (27), may be cast into the Fisher form by denoting dV/d¸ as

V

, and rewriting it as V

+ zV

+ ¸V

2

+ oV + c = 0 where 15

z=

(v

2

0

− c

2

0

a

2

)L

R

2

a

2

v

0

, ¸=

bR

1

a

2

R

2

, o=

−R

1

R

2

a

2

, and c=

R

1

R

2

1

4ba

2

−

d

0

L

R

2

a

2

v

0

. (30)

We deﬁne a change of variable V = :W + [, where : and [ are chosen as 17

: =

−

_

o

2

− 4¸c

¸«

and [ =

−o +

_

o

2

− 4¸c

2¸

. (31)

Hence the traveling wave solution found is 19

V =

1

2b

+

_

d

0

L

bR

1

v

0

_

¸

_

¸

_

1 − 2

_

_

_

1 + p exp

_

_

_

q

¸

¸

¸

_

2

a

2

R

2

_

bd

0

R

1

L

v

0

¸

_

_

_

_

¸

_

−s

_

¸

_

¸

_

. (32)

The propagation velocity for the traveling kink solution is 21

¯ v =

D(v

2

0

− v

2

max

)L

R

2

a

2

v

0

. (33)

The velocity of ion ﬂows in physiological situations, such as action-potential propagation 23

[1], ranges between 0.1 and 10 m/s; hence we estimate the corresponding nonlinear wave

velocities, ¯ v, to be 1 m/s¯ v100 m/s. Actin interacts with a number of ion channels, of 25

different ionic permeability and conductance. Thus, it is expected that channel opening,

single-channel currents and other channel properties, including the resting potential of the 27

cell, may signiﬁcantly modify the amplitude and velocity of the soliton-supported waves.

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3. Microtubules 1

In this section, we give two examples of microtubule dynamics that are dominated by

nonlinearity. 3

3.1. MT polymerization in reduced gravitational ﬁelds

Space-ﬂight laboratory experiments have shown that the in vitro and in vivo self- 5

organization of MTs is sensitive to gravitational conditions. In a previous work, we have

proposed a model of self-organization of MTs in a gravitational ﬁeld [24]. This reaction 7

diffusion model was based on the dominant chemical kinetics and on the interplay between

the diffusion processes and the drift induced by gravitational ﬁelds. We have considered as 9

chemical kinetics, the nucleation of ﬁlaments and the elimination of the nucleation center,

the elongation and the shrinking of ﬁlaments, the recycling of GDP-tubulin in GTP-tubulin. 11

It has been demonstrated that the polymerization of MTs proceeds in a traveling wave

fashion propagating with a constant velocity v. The tubulin concentration, C, as a function 13

of the moving coordinate, ¸ = x − vt , describes a polymerization wave as follows:

C = 2

−2/n

_

1 − tanh

_

n

2

√

2n + 4

(¸ − ¸

0

)

__

2/n

, (34)

15

where ¸

0

is an arbitrary constant and n represents the number of dimers involved in the

nucleation center. The wave velocity v is dependent on n, v =−(n+4)/(

√

2n + 4)

√

D

c

k

1

17

with D

c

the diffusion coefﬁcient of tubulin dimers, and k

1

the recycling rate of GDP-tubulin

in GTP-tubulin. The nucleation process has been classically described as the power of the 19

GTP-tubulin concentration with nucleation exponents ranging from 6 to 12. This term

represented the strongest nonlinearity of the model. 21

3.2. The bending dynamics of MTs

In this section, we represent an MT as an elastic rod which can undergo large bending 23

motions. We ﬁrst deﬁne the arc length, s, belonging to [0, L], where L is the MT length,

0(s, t ) is the tangent angle to the MT at position s and at time t . At time t , the curvature, 25

1/R

c

, of the MT at the position s is 1/R

c

=j0/js where R

c

is the radius of curvature. The

Lagrangian density can be expressed in terms of 0 as follows [5]: 27

L=

I

2L

_

j0

jt

_

2

−

_

«

f

2

_

j0

js

_

2

− F cos 0

_

, (35)

where I is the moment of inertia and «

f

is the ﬂexural rigidity [13]. The term(I/2L)(j0/jt )

2

29

represents the kinetic energy density, where j0/jt is the angular velocity. The second term,

(«

f

/2)(j0/js)

2

, is the local elastic potential energy, and the third term, −F cos 0 measures 31

the energy density expended in applying a force, F, to the MT. The moment of inertia, I, of

a rod, representing an MT, around an axis perpendicular to its length and passing through 33

one of its ends, is given by I = ¯ mL

2

/3, where ¯ m is the total mass of an MT of length L.

U

N

C

O

R

R

E

C

T

E

D

P

R

O

O

F

10 J. Tuszy´ nski et al. / Nonlinear Analysis ( ) –

NA4432

ARTICLE IN PRESS

The dynamics of the bending of an MT resulting from the Euler–Lagrange equation is 1

expressed by the nonlinear wave equation

−

I

L

j

2

0

jt

2

+ «

f

j

2

0

js

2

− F sin 0 = 0 (36)

3

where the propagation velocity of the bending wave is v=

√

«

f

L/I. The change of variables,

˜ x =

_

F

«

f

s and

˜

t =

_

FL

I

t , rescales Eq. (36) to

5

j

2

0

jt

2

−

j

2

0

jx

2

= −sin 0, (37)

where the tildes are omitted for simplicity. Eq. (37) has the form of the unperturbed Sine- 7

Gordon equation. It has one particularly important solution taking the formof a kink [15,20],

0(x, t ) = 4 tan

−1

_

_

_

exp

_

_

_

±(x − vt − x

0

)

_

1 − (v/v

m

)

2

_

_

_

_

_

_

, (38)

9

where v

m

is the maximum phonon velocity. In addition, the Sine-Gordon equation [8] has

an inﬁnity of multi-soliton solutions T , but their physical signiﬁcance is unclear. 11

4. Summary and conclusions

Nonlinearities are very important in the physical description of several key biomolecules 13

that participate in a crucial subcellular processes, namely actin, MTs and motor proteins (es-

pecially kinesin). We showed in this paper that the assembly kinetics of actin is a nonlinear 15

process that requires not only a mechanism of saturation but also annealing and fragmen-

tation that are governed by coupled nonlinear equations involving monomer concentration 17

and ﬁlament number as the key variables. The observed dendritic growth of actin networks

in cell motility phenomena is subsequently described by the coupling of actin ﬁlaments to 19

the protein calledArp2/3. Next, we discussed howcoupled differential equations describing

the interactions between ions in solution and ions on the ﬁlament can lead to solitonic signal 21

transmission.

We then discussed the role of nonlinear dynamics in the formation of MTs. First of all, 23

it has been known for more than a decade that high concentration of the constituent protein

tubulin leads to self-sustained oscillations in the assembly and disassembly dynamics of 25

MTs. We proposed a model of self-organization of MTs in a gravitational ﬁeld. The model

is based on the dominant chemical kinetics. The pattern formation of MT concentration is 27

obtained (1) in terms of a moving kink in the limit when the disassembly rate is negligible,

and (2) for the case of no free tubulin and only assembled MTs present [24]. The results of 29

our simulations are in good quantitative agreement with experimental data.

We presented a continuous medium model of the elastic properties of MTs that includes 31

large bending motions of MT ﬁlaments by describing a MT as an elastic rod. We found

that when a MT is subjected to bending forces, the tangent angle satisﬁes a Sine-Gordon 33

U

N

C

O

R

R

E

C

T

E

D

P

R

O

O

F

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ARTICLE IN PRESS

J. Tuszy´ nski et al. / Nonlinear Analysis ( ) – 11

equation. Particular analytical solutions of this equation describe kink and anti-kink bending 1

modes that may propagate at a range of velocities along the length of the MT.

References 3

[1] B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, Essential Cell Biology: An

Introduction to the Molecular Biology of the Cell, Garland Science Publishing, London, 1998. 5

[2] B. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, J.D. Watson, Molecular Biology of the Cell, third ed.,

Garland Publishing, London, 1993. 7

[3] L.A. Amos, W.B. Amos, Molecules of the Cytoskeleton, ﬁrst ed., MacMillan Press, London, 1991.

[4] J.M. Buzan, C. Frieden, Proc. Natl. Acad. Sci. USA 93 (1996) 91. 9

[5] S. Caspi, E. Ben-Jacob, Europhys. Lett. 47 (1999) 522.

[6] G. Civelecoglu, L. Edelstein-Keshet, Bull. Math. Biol. 56 (1994) 587. 11

[7] J.A. Cooper, E.L.B. Jr., S.B. Walker, T.Y. Tsong, T.D. Pollard, Biochemistry 22 (1983) 2193.

[8] R.K. Dodd, J.C. Eilbeck, J.D. Gibbon, H.C. Morris, Solitons and Nonlinear Wave Equations, Academic Press, 13

NewYork, 1982.

[9] L. Edelstein-Keshet, Eur. Biophys. J. 27 (1998) 521. 15

[10] H.P. Erickson, J. Mol. Biol. 206 (1989) 465.

[11] C. Frieden, Proc. Natl. Acad. Sci. USA 80 (1983) 6513. 17

[12] C. Frieden, D. Goddette, Biochemistry 22 (1983) 5836.

[13] J. Howard, Mechanics of Motor Proteins and the Cytoskeleton, Sinauer Associated Inc., 2001. 19

[14] P. Janmey, U. Euteneuer, P. Traub, M. Schliwa, J. Cell Biol. 113 (1991) 155.

[15] C. Kittel, Introduction to Solid State Physics, Wiley, NewYork, 1956. 21

[16] J. Kolosick, D. Landt, H. Hsuan, K. Lonngren, Proc. IEEE 62 (1974) 578.

[17] A. Lader, H. Woodward, E. Lin, H. Cantiello, METMBS’00 International Conference 77–82. 23

[18] E. Lin, H. Cantiello, Biophys. J. 65 (1993) 1371.

[19] K. Lonngren, Observations of solitons on non-linear dispersive transmission lines, Solitons in Action, 25

Academic Press, London, NewYork, 1978, 127–152.

[20] P. Meurer-Grob, J. Kasparian, R. Wade, Biochemistry 40 (2001) 8000. 27

[21] A. Noguchi, Elec. Comm. Japan 57 (1974).

[22] F. Oosawa, S. Asakura, Thermodynamics of the Polymerization of Protein, Academic Press, London, New 29

York, 1975.

[23] T.D. Pollard, J. Cell Biol. 103 (1986) 2747. 31

[24] S. Portet, J.A. Tuszy´ nski, J.M. Dixon, M.V. Satari´ c, Phys. Rev. E 68 (2003) 021903.

[25] D. Schafer, P. Jennings, J. Cooper, J. Cell Biol. 135 (1996) 169. 33

[26] L.S. Tobacman, E.D. Korn, J. Biol. Chem. 258 (1983) 3207.

[27] J.A. Tuszy´ nski, S. Portet, J.M. Dixon, C. Luxford, H.F. Cantiello, Biophys. J. 86 (2004) 1890. 35

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[29] A. Wegner, P. Savko, Biochemistry 22 (1982) 1909. 37

[30] C.H. Wiggins, Math. Meth. Appl. Sci. 24 (2001) 1325.

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