ISSN 2347-6893

REORGANIZATION OF ACTIN FILAMENTS AND MICROTUBULES BY

ABSTRACT
A theoretical study of the polymerization process of a cytoskeleton by an outside electric field is presented. We describe
the reaction kinetics of polymerization of the cytoskeleton by Einsteins approximation. The thermodynamic study of the
equilibrium constant of the reaction kinetics shows the possibility of the reorganization of the cytoskeleton by the outside
electric field. We show an effective stimulation of the polymerization which is connected to the effective value of the
electric field and can certainly be modified by modulation of the carrier frequency.

Indexing terms/Keywords
Cytoskeletal polymerization; modulated electric field

Council for Innovative Research

Journal: JOURNAL OF ADVANCES IN BIOLOGY

November 02, 2015

ISSN 2347-6893
INTRODUCTION
The biophysical (biomechanical, bioelectrical, thermodynamic, etc.) properties of cells and their networks are studied
intensively. This research is especially extended to understand the changes of these properties in various diseases.
Cancerous cells attract huge attention from researchers, because the cellular changes and the network changes are
obviously connected to one another. Twenty prestigious laboratories in the USA formed a research network (The Physical
Sciences Oncology Centers Network) to study these phenomena together. Their report about a complex study of
malignant and benign tumour-cell behaviours [1] is probably a milestone in this research. They observed definite and
decisive differences between the mechanical, adhesion, and migration properties of the non-tumorigenic MCF-10A and
metastatic MDA-MB-231 breast epithelial cell-lines, based mostly on multi-omics approaches. The huge motility of cancer
cells is probably connected to the lazy polymerization of the cytoskeleton [2], which promotes huge deformability in
cancerous cases. The metastatic potential grows with increasing motility and high deformability [3]. Not only the cells but
also their extracellular milieu have [4] importance in the metastatic motility, showing a promoting role of the rigid
extracellular matrix. However, the high motility is probably due to the loss of the polymerization order of the cytoskeleton
[5], which makes the cells especially soft and movable [6].
Due to the importance of the appropriate polymerization of the cytoskeleton, we propose to enhance the polymerization
with a modulated electromagnetic signal.

METHOD
The stoichiometric equation describing polymerization in reaction kinetics shows the following:

Mi M

M i 1

(1)

This kinetics could be formulated by the following reaction-kinetic equation:

d M i1
ke M i M kv M i1
dt
where [] denotes the concentrations, and
chemical equilibrium we have

k e and k v

(2)

are the speed constants of the forward and backward processes. In

d M i 1
0 , and in consequence the equilibrium constant of the reaction:
dt

k v M i M

K
M i 1
ke

(3)

We study how the character of this reaction changes in an electromagnetic field and how it depends on the frequency and
amplitude of the applied effects.
For a complete thermodynamic description, we consider three components of the system. Each component has its own
polarizability interacting with the outside field. In this case the first law of thermodynamics is:

dU TdS pdV
1dN1 2 dN 2 3 dN 3 EdP1 EdP2 EdP3
where

1 , P1 , and dN1

P2 , and dN 2

(4)

are the chemical potential, polarization, and particle number of the i-range polymer M i ;

are the chemical potential, polarization, and particle number of the monomer

; and 3 ,

2 ,

P3 , and dN 3

are the chemical potential, polarization, and particle number of the i + 1 range polymer M i 1 . The difference is defined by
the reaction during the time dt and E is the electric-field strength caused by the outside manipulation from independent
sources. We consider the reaction at constant pressure and temperature (isobar and isotherm) and so we can introduce
the free enthalpy as:

dG dU TdS pdV
1dN1 2 dN 2 3 dN 3 EdP1 EdP2 EdP3

(5)

The condition of the polymerization equilibrium is when K = 0 in (3). In this case we have an extreme problem with the
definite stoichiometric condition described in (1). Introducing a reaction coordinate ,

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dN1 d ,

dN 2 d , dN 3 d

(6)

Suppose that the polarization of the various components is proportional to the number of particles in the component:

dP1 p1 dN 1 p1 d , dP2 p 2 dN 2 p 2 d ,
dP3 p 3 dN 3 p 3 d

(7)

Then using (5), for equilibrium we obtain

dG 1 E p1 2 p 2 E 3 p 3 E d 0

(8)

1 E p1 2 p 2 E 3 p 3 E 0
When the actual time constants are smaller than the outside frequency, this equation is time-independent and so it is valid
every time, so it has to be true for the average too:

(9)

1 E p1 2 p 2 E 3 p3 E dt 0
0

where is the periodic time of the excitation. We suppose that the chemical potentials are constant during the averaging,
even though their values depend on the concentrations of the three components. This condition means that the timeconstant of the changes of chemical potential is definitely longer than the time constant of the exciting effect. (They are not
able to follow the changes of the excitation promptly.) Consequently,

(9)

1 E p1 2 p 2 E 3 p 3 E dt
0

1 2 3

E p

p 2 E p 3 E dt 0

The chemical potentials in the ideal-gas approximation are approached:

1 10 kT ln[ M i ], 2 20 kT ln[ M ],

(10)

3 30 kT ln[ M i 1 ]
where

i0 , i 1,2,3

are the chemical potentials characterizing the unit concentration, and these can depend on the

temperature. Substituting these into (9):

10 20 30 kT ln
where

M i M

M i 1

E p1 p 2 E p 3 E 0

(11)

means the time-average. Consequently, the equation for reaction-kinetics using the equilibrium constant from

(3) is:

[ M i ][ M ] k v

K e
[ M i 1 ]
ke

K0e

K0 e

10 20 30
kT

E p1 p 2 p3
kT

(12)

E p1 p 2 p3
kT

10 20 30
kT

RESULTS
The equilibrium constant when the electric field is zero is

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2 3
1
kT
e
0

[ M i ][M ] k v

K
[ M i 1 ]
ke

(13)

K 0 (T )
Let us suppose that the polymerization effect of tubulins (which build the structure) at the temperatures

kv

and

ke

will

decrease and increase with temperature, respectively. Consequently, from (13),

1 2 3

(14)

In consequence of (12), the effect of E p1 p2 p3 0 has the same process (growing length of tubulins), while in the

case of E p1 p2 p3 0 , the opposite occurs. When the polarization is proportional to the field, then:

[ M i ][ M ] k v

K e
[ M i 1 ]
ke

K0e
When

2
1 2 p 3
E eff

kT

1 2 3 0 , then k v

10 20 30
kT

E p1 p2 p3
kT

p i i E , i 1,2,3,
decreases and

ke

(15)

2
E eff
E2

increases, so the field supports the polymerization. In the reverse

case the outside field will dismount the cytoskeletal network.

with angular-frequency

is

ut U 0 1 m sin t sin 0 t

(16)

where m is the modulation depth. The spectrum is shown in Figure 1.

Figure 1. Spectrum of a carrier amplitude modulated by a harmonic frequency

U 02
U2
m2 0
2
4

(17)

In consequence, the modulation increases the effective value of the electric field, and with this supports the reorganization
of the cytoskeletal network according to (15). When the modulation is noise, then this effect is stronger, due to the nondiscrete spectral frequencies, but a continuous spectrum is applied.
Let us study an example with a modulated signal of:

ut xt U 0 sin 0 t
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(18)

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where x(t) is pink noise (time-fractal pattern).
When the power spectrum of the pink noise in the frequency interval

, has the form of

X X

(19)

then the effective value of the modulated signal is:

This shows that at

a 0 , ueff2 .

f
U 02
2 A ln
2
a

(20)

Consequently, this type of modulation is excellent for reorganizing the

cytoskeletal network.

DISCUSSION
The microtubules of the cytoskeletal network could be described by a polymer which Einstein proposed [7], [8]. It has a
specialty that only a single chemical bond is allowed to be formed between the monomer and the prepared polymer. The
reaction steps of this process are a chain polymerization (Einsteins polymer). This model is not able to describe the multibonding processes when the chemical bonds could have branches in the tubulins (multi-strands). When multi-bonding is
allowed, the bonds can be active inside a strand or between them, making various space-filling structures.
The polymerization steps of linear polymers can be described by equilibrium constants:

K1

M M , K M 2 M ,..., K M n M
2
M 2
M 3
M n 1

(21)

The polymerization steps in Fig. 3 need the following equilibrium constants:

K1

M M , K

M M , K
'

M
2

M M ,..., K M M , K M M

M
M
M (22)

n 1

n 1

These equilibrium constants can differ. The reorganization stimuli are valid for these multi-strand cases too, but the multistrands have longer chains than the mono-strand does. This is because the multi-strand polymer has multiple free ends
and energy centres, so these are less favourable from an energy point of view. According to the Boltzmann statistical
considerations a system with multi-strand chains will have a lower concentration than one with mono-chains. On the other
hand there is a connection between the concentration of polymer

M n

and its length expressed in the number of

monomers n from which it is constructed, expressed as

M n e
where

n0

n
n0

(23)

is constant. Consequently, the low concentration has longer polymers.

CONCLUSION
We have shown the possibility of polymerization support of the cytoskeleton. This effect is especially important in the case
of cancer cells, where the destabilized and incompletely polymerized cytoskeleton has the role of allowing higher motility
of these cells, promoting the metastatic spread. Our method is applied well in practice, where we use fractal noise for
proper action [9]. Our approach using noise is similar to the harmonizing method [10], whose application is emerging in
physiology [11].

REFERENCES
[1] Agus, D.B., Alexander, J.F., Arap, W., Ashili, S., Aslan, J.E., Austin RH, [Link]. 2013. The Physical Sciences - Oncology
Centers Network, A physical sciences network characterization of non-tumorigenic and metastatic cells, Scientific Reports
3:1449, doi:10.1038/srep01449.
[2] Suresh, S. 2007. Biomechanics and biophysics of cancer cells, Acta Biomaterialia 3:413438.

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[3] Wirts, D., Konstantopoulos, K., Searson, P.C. (2011) The physics of cancer: the role of physical interactions and
mechanical forces in metastasis, Nature Reviews, Cancer 11:512518.
[4] Uklrich, T.A., Pardo, [Link]., Kumar, S. 2009. The mechanical rigidity of the extracellular matrix regulates the
structure, motility, and proliferation of glioma cells, Cancer Res. 69:41674175.
[5] Friedman, E., Verderame, M., Winawer, S., Pollack, R. 1984. Actin cytoskeletal organization loss in the benign-tomalignant tumor transition in cultured human colonic epithelial cells, Cancer Res. 44:30403050.
[6] Plodinec, M., Loparic, M., Monnier, C.A, et al. 2012. The nanomechanical signature of breast cancer, Nature Nanotech.
7, 757765, [Link]
[7] Einstein, A. 1906. On the theory of Brownian movement. Ann. Phys. 19, 371381.
[8] Condeelis, J., Hall, A., Bresnick, A., Warren, V., Hock, R., Bennett, H., Ogihara, S. 1988. Actin polymerization and
pseudopod extension during amoeboid chemotaxis; Cell Motility and the Cytoskeleton 10:7790.
[9] Szasz, A. 2013. Challenges and solutions in oncological hyperthermia, Thermal Med. 29(1):123.
[10] Springer, M., Paulsson, J. 2006. Harmonies from noise, Nature 439:2728.
[11] West, J.B. 2013. Fractal physiology and chaos in medicine, World Scientific.

Author biography with Photo

Curriculum Vitae

Andras SZASZ

PERSONAL
1947. November 04.

Born in Budapest, Hungary

STUDIES
1967-72

Studies at Etvs University (Physics) [MS graduation, thesis: Positron annihilation]

1974

Doctors degree at Etvs University (Physics)

1983

Candidate of Mathematical and Physical Sciences of Russian Academy of Sciences, (Surface physics)

1983

Candidate of Physical Sciences of Hungarian Academy of Sciences (Physics)

1996

Habilitation at St. Istvan University (Hungary) (Biophysics)

ACADEMIC APPOINTMENTS
1972-1974:

Assistant professor in Eotvos University Budapest, Hungary

1974-1982:

Associate professor in Eotvos University Budapest, Hungary

1982-1985:

Head of Metalab and Laboratory of Surface Physics in Eotvos University

1985-1986:

Head of Dept. Solid State Physic, Eotvos University Budapest, Hungary

1986-1987:

Research fellow Scottish Surface Centre, Strathclyde University, Glasgow, UK

1988-2004:

Appointed visiting professor to Material Engineering Department of Strathclyde University, Glasgow, UK

1996-cont.

Professor at St. Istvan University, Gdll, Hungary (biophysics)

2012-cont.

Appointed visiting professor, Pazmany Catholic University, Hungary (bioelectrodynamics)

2013-cont.

Appointed visiting professor at Chiba University, Japan (fractal physiology)

PRESENT ADMINISTRATIVE POSITIONS

Head of Biotechnics Department in St. Istvan University, Faculty of Engineering. Hungary

2001-cont.

CSO of OncoTherm ([Link] ) (both the Hungarian and German Branches)

SCIENCE AWARD
2000

Dennis Gabor Award (Hungarian Academy of Science)

PUBLICATIONS
Author and co-author of about 700 publications (articles, conference contributions/abstracts), co-author of eight
books, and co-author of 40+ patents

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