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AIP ADVANCES 2, 011207 (2012)
Physical aspects of biological activity and cancer
Jiˇ
r´
ı Pokorn´
ya
Institute of Photonics and Electronics AS CR, Chabersk´
a 57, Prague 8, Czech Republic
(Received 1 September 2011; accepted 14 October 2011; published online 22 March 2012)
Mitochondria are organelles at the boundary between chemical–genetic and phys-
ical processes in living cells. Mitochondria supply energy and provide conditions
for physical mechanisms. Protons transferred across the inner mitochondrial mem-
brane diffuse into cytosol and form a zone of a strong static electric field changing
water into quasi-elastic medium that loses viscosity damping properties. Mitochon-
dria and microtubules form a unique cooperating system in the cell. Microtubules
are electrical polar structures that make possible non-linear transformation of random
excitations into coherent oscillations and generation of coherent electrodynamic field.
Mitochondria supply energy, may condition non-linear properties and low damping
of oscillations. Electrodynamic activity might have essential significance for ma-
terial transport, organization, intra- and inter-cellular interactions, and information
transfer. Physical processes in cancer cell are disturbed due to suppression of oxida-
tive metabolism in mitochodria (Warburg effect). Water ordering level in the cell is
decreased, excitation of microtubule electric polar oscilations diminished, damping
increased, and non-linear energy transformation shifted towards the linear region.
Power and coherence of the generated electrodynamic field are reduced. Electromag-
netic activity of healthy and cancer cells may display essential differences. Local
invasion and metastastatic growth may strongly depend on disturbed electrodynamic
activity. Nanotechnological measurements may disclose yet unknown properties and
parameters of electrodynamic oscillations and other physical processes in healthy
and cancer cells. Copyright 2012 Author(s). All article content, except where other-
wise noted, is licensed under a Creative Commons Attribution 3.0 Unported license.
[http://dx.doi.org/10.1063/1.3699057]
I. INTRODUCTION
In the twenties of the last century Warburg et al.1disclosed suppression of oxidative metabolism
in living cells caused by mitochondrial dysfunction and suggested its connection with diminished
order in the cell (Warburg2). In 1967 M. Marois organized the first Versailles meeting entitled “The-
oretical Physics and Biology” where H. Fr¨
ohlich3presented the idea of correlation over macroscopic
regions and creation of macroscopic wave function in biological systems. Non-linear interactions
between elastic and electric polarization fields and non-linear spectral energy channeling may lead to
establishment of coherent oscillation states in systems with energy supply.4–6Cooperative phenom-
ena in systems far from thermodynamic equilibrium (synergetics) were analyzed by Haken.7Pohl,8
H¨
olzel and Lamprecht,9and H¨
olzel10 observed attraction of dielectric particles to living cells. The
dielectric particle may move to and from the cell in dependence on the difference of the permittivity
of the particle and the medium. The amount of attracted particles depends on their permittivity,
conductivity of the suspending liquid, shape of the cell (enhanced attraction to the tips of elongated
cells), and on the cell cycle (increased attraction in the M phase of the cell cycle). It was not clear,
what cellular structures are responsible for the measured electrodynamic activity. Microtubules fulfill
conditions for generation of the oscillating electromagnetic field (Pokorn´
yet al.11,12). The field was
measured at the membrane in the frequency range 8–9 MHz (Pokorn´
yet al.13). Sahu et al.14 claims
aE-mail: pokorny@ufe.cz.
2158-3226/2012/2(1)/011207/11 C
Author(s) 20122, 011207-1
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that microtubules in vitro display resonance at the frequency of about 10 MHz. It might be important
discovery of microtubule properties. Kirson et al.15,16 proved that microtubule polymerization may
be interrupted by external electromagnetic field in the frequency range 100–300 kHz with intensity
of the electric field 1–2 V/m. The forces exerted by the external field on tubulin heterodimers pre-
vent their correct orientation and attraction to the close vicinity of the tip and disturb transport of
tubulin heterodimers to the growing microtubule end. Vedruccio and Meessen17 observed increased
damping of the external electromagnetic field in cancers at the frequency of about 465 MHz and its
first and second harmonics if the radiating antenna is placed in the vicinity of the tumor. The effect
corresponds to microtubule energy oscillation losses in cancer cells (Pokorn´
yet al.18). Oscillation
of microtubules seems to be a fundamental mechanism for generation of the cellular electrody-
namic field. Cooperation between mitochondria and microtubules may form convenient conditions
for excitation (Pokorn´
yet al.19). The generated field might play a role in organization, transport,
interactions (Pokorn´
y,20,21 Pokorn´
yet al.22), and information transfer. Dysfunction of mitochondria
in cancer cells may disturb internal cellular electrodynamic field with consequences to biological
functions based on physical processes (Pokorn´
yet al.19 and Pokorn´
y23,24). Conditions for excitation
of the cellular electrodynamic field are described in this paper.
II. INTERFACIAL WATER ORDERING
For a long time organization of water was a controversial issue. Hydration was assumed to be
limited to several water layers. Bulk water (i.e. water without ordering) was assumed to be in living
cells. But ordering of the intracellular water is a crucial phenomenon affecting its elasto-electrical
properties. Experimental results have gradually brought essential evidence for this phenomenon.
Significant increase of the NMR (nuclear magnetic resonance) spin–lattice relaxation time (T1)in
cancer cells was explained by decrease in water ordering of the intracellular water (Damadian25).
Zones without solutes were observed around microtubules. These clear zones were assumed to be
occupied by a coating of proteins that prevent large particles approaching the microtubule surface
(Amos26). Stebbings and Hunt27 connected formation of clear zones with the negative charge at
the microtubule surface. The biomolecules and structures carry electric charge at their surfaces,
and, therefore, the ordering of water should be a general phenomenon. Ling28 formulated theory
of ordering of water molecules caused by electrostatic field of the surface charge at the interface.
Zheng and Pollack29 and Zheng et al.30 observed clear (exclusion) zones that excluded solutes up
to a distance of the order of magnitude of 0.1 mm. The electric potential across the exclusion zone
is dependent on the ion concentration in the solution. The measured potential difference across the
exclusion zone is of about 100 mV. Thermal motion in the exclusion zone is lowered as follows from
suppressed infrared radiation (in the range 3.8–4.6μm) from the zone extending from the sample
surface up to a distance of 0.3–0.5 mm. UV absorbance at 270 nm is increased. Molecules of the
ordered water are organized in plane layers parallel with the surface in the case of a flat interface.
Ordered water has different physical properties in comparison with the bulk water, in particular
higher viscosity (Pollack et al.31), different pH (Chai et al.32 ) and spectroscopic properties (Chai
et al.33), and separation of charge (Chai et al.32). More detailed information about ordered water
properties may be found in Pollack et al.31 Infrared radiation promotes formation of the exclusion
zones (Chai et al.32). Ordering of water in living cells may depend on the phase of the cell cycle.
NMR spectroscopy disclosed increased level of water ordering in the metaphase period of the M
phase (Zimmerman et al.34).
Ordering of water is not limited to hydrophilic interfaces. The main agent in water ordering is
the electric field. A strong electric field about 500–700 kV/m causes water ordering and forms a
floating water bridge about 1–3 cm long between two glass beakers (Fuks et al.35–37 and Giuliani
et al.38).
Theoretical explanation of creation of the ordered water layer based on quantum electrodynamics
was worked out by Preparata39 and Del Giudice et al.40 The “normal liquid” water contains two
mixed phases: coherent domains whose linear dimension may be of about 100 nm and a gas-like
phase. Coherent domains form the ordered water. Static electric field organizes coherent domains
into exclusion zones. Organization structure of coherent domains is transferred by the action of
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the electric field into exclusion zone that is a macroscopic entity. Exclusion zone features may
correspond–to some extent–to a transition structure between a liquid (that makes possible diffusion
of protons) and a solid state material including quasi-free electrons. Del Giudice et al.40 and Del
Giudice and Tadeshi41 suggested that the free electrons (“electron conductivity”) of exclusion zones
may have a strong impact on cell behavior.
III. MITOCHONDRIAL FUNCTION
Mitochondria are employed in energy supply system in the cell. Energy from pyruvate produced
by fermentation and fatty acids is parceled out into small packets and then stored into ATP and
GTP (adenosine and guanosine triphosphate) for biological utilization. In the process of ATP and
GTP production chemical energy is converted into electrochemical proton gradient. Protons are
transported outside the mitochondrial matrix space across the inner membrane and diffuse through
the outer membrane into the mitochondrial surroundings creating a space-charge layer. The protons
transported across the inner membrane serve not only for storage of energy and its splitting but
also–together with the negative charge in the mitochondrial matrix space–for formation of the static
electric field around mitochondria. Each mitochondrion is surrounded be a layer of a strong static
electric field. Tyner et al.42 measured intensity of the static electric field by fluorescent spherical
particles 30 nm in diameter. Emission ratios at two different wavelengths of the fluorescent spectrum
depended on the intensity of the electric field. When the results were analyzed complications caused
by a short distance between mitochondria appeared. Very often the fluorescent particles measured
the field generated by several mitochondria located in their vicinity, in particular in the plane above
and below the observed one. Some measured values were assumed to represent the cytosolic region
(not influenced by several mitochondria). Fig. 1shows intensity of the static electric field up to a
distance of 2 μm from a mitochondrial membrane.
The intensity values (after Tyner et al.42 ) are plotted as the black rectangles with a regression
long dash line segment. The measured intensity was considered to yield the cytosolic values, i.e.
the values from the regions that do not cross over other mitochondrial fields. The intensity of
the static electric field displays nearly linear dependence on the distance from the mitochondrial
membrane. Theoretical curve of the intensity of the static electric field in cytosol determined from
the distribution of proton charge is plotted in the full line. The values drop significantly and rapidly
near the mitochondrion and beyond a distance of the order of magnitude 10 nm they are much
smaller than the measured ones. Therefore, it may be reasonable to assume that the cytosolic water
around mitochondria is ordered as around the charged surfaces of biopolymer structures (interfacial
ordering). For a planar parallel and a spherical organization of the model of ordered water the
intensity of the static electric field is plotted in the dotted and the short dash curves, respectively. The
measured intensity of the static electric field is in between these two limit curves. But the exclusion
zone may be non-uniform and protons may diffuse into the ordered layer. Zheng et al.30 assumed
that the fact that the solute exclusion zones of 0.36 mm could be found in 150 mM salt solution
argues against a purely electrostatic mechanism. But the ions may be expelled from the ordered
region of cytosolic water and concentrated beyond the distant edge of the ordered region (diffusion
may smear the boundary). Charge distribution depends on its concentration and on the intensity of
the static electric field in the ordered region. Water ordering is a phenomenon changing water from
a viscosity liquid to quasi-elastic gel affecting inner cellular processes, in particular providing low
damping of the cytoskeleton vibration system.
But the assumption that the measured static field is generated only by one mitochondrion is very
likely not fulfilled. Mitochondria occupy about 22 % of the cellular volume. There may be about
1000 (or more) mitochondria in a cell. For spherical mitochondria of about 0.6 μm in diameter the
average distance between mitochondria is of about 0.4 μm. Exclusion zones around mitochondria
may mutually cross over one another. Protons may be concentrated in the boundary regions where is
the minimal value of the intensity of the electric field of the overlapping ordered layers of different
mitochondria. The protons form diffuse layers between mitochondria. (The distribution of protons
and dynamic equilibrium of their flow between the layer and the mitochondrial inner membrane
deserve a detailed analysis.) Therefore, the cytosolic medium is under influence of a strong static
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FIG. 1. Distribution of protons and electrostatic field in the vicinity of mitochondria. Black squares – experimental values
of the intensity of the cytosolic electrostatic field measured by fluorescent particles (after Tyner et al.42) with the regression
long dash line segment. The full line (C) – the classical theoretical curve of the intensity dependent on the proton distribution
in the cytosol without considering ordered water layer. The dotted line (P) and the short dash curve (S) – intensity of the
electric field in the ordered layer of water assuming distribution of opposite charges in the parallel plane layers and in the
spherical symmetrical layers, respectively.
electric field that polarizes biological macromolecules and structures and shifts oscillation processes
into highly non-linear regions.
Energy entering mitochondria is used for production of ATP and GTP with the efficiency of
about 40 % or slightly greater. The non-utilized energy that may reach nearly 60 % (often denoted
as the “wasted” energy) is liberated from mitochondria into cytosol in the form of photons in the
UV (Tilbury and Quickenden,43 Batyanov44,45 ), visible, and infrared region, chemical compounds,
and heat.
IV. CELLULAR ELECTROMAGNETIC FIELD
The eukaryotic cell cytoskeleton is a highly dynamic structure that reorganizes continuously
in response to cell changing shape, division, and environmental conditions. The cytoskeleton has
a wide spectrum of functions. It organizes the cell, keeps its geometric stability, participates in
cell motility, makes possible ribosomal and vesicle transport, has a special role in mitosis, and
transduces pressure and tension. The cytoskeleton is composed of microfilaments, intermediate
filaments, microtubules, and accessory proteins. All the cytoskeleton parts are mutually connected
and form a three-dimensional network in the cell. The center of the cytoskeleton is the centrosome.
Microtubules start to polymerize at the centrosome in radial direction. In the interphase some of them
are connected to proteins at the membrane. In the M phase microtubules form a mitotic spindle with
two poles (centrosomes). In the interphase mitochondria may be aligned along microtubules. In the
M phase mitochondrial distribution is not known. Organization of mitochondria might be a special
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issue of the cellular static electric and electromagnetic field. The cell may form an electromagnetic
cavity resonator with dielectric walls. The position of the microtubules and the centrosome may
be controlled by the cavity electromagnetic field. The space distribution of the field and the acting
forces are different in the interphase and in the M phase (in the one pole and the two poles structure,
respectively). Mitochondria may move together with the ordered water and the proton space charge
layer. The final effect may be assessed using real parameters of the system. Therefore, effect of
the cellular electromagnetic field on mitochondrial organization remains an open question. On the
other hand the static electric field might participate in mitochondrial space distribution too. Very
often mitochondria remain in position where they cover unusually high ATP consumption. Due
to the proton transfer and the strong static electric field mitochondria might provide a long range
interactions with the “energy consumption site”. The sites of increased energy consumption in the
M phase have different locations in comparison with the interphase period.
Microtubule is a cylindrical structure formed by protofilaments composed of tubulin het-
erodimers. A tubulin heterodimer consists of two globular proteins. Both have a relative molecular
mass of about 55000, but their masses are not equal. Each heterodimer is an electric dipole whose
dipole moment is of about 1000 Debye (10-26 Cm)–Satari´
cet al.46 and Tuszy´
nski et al.47 The induced
dipole moment per dimer arising only from the motion of mobile electrons or protons was estimated
to be 200–400 Debye (Stracke et al.48). Mechanical oscillations are connected with polarization
changes.
Energy is supplied into microtubules. The microtubules are dynamic polymers that display
dynamic instability. In the interphase the microtubules connected to the structures at the cellular
membrane have a turnover of about 18 hours (Pelling et al.49). After this period they are replaced by
other microtubules. The microtubules with the free end have a turnover of about 10 min. They are
growing and shrinking. After polymerization GTP in the βtubulin is hydrolyzed to GDP (guanosine
diphosphate) and a part of the released energy is stored in the microtubule structure. In the M
phase microtubules polymerize in the central part and depolymerize at the poles of the mitotic
spindle (this process is called treadmilling). Both mechanisms of dynamic instability supply energy
to microtubules.
Motor proteins transporting “cargo” move along microtubules. A part of the energy of motion is
transferred to the microtubules. But the motor proteins might also cause disturbances and damping
of microtubule oscillations. In the interphase the greatest energy supply to microtubules is very
likely provided by non-utilized energy liberated from mitochondria (Pokorn´
yet al.18).
Frequency spectrum of biological electrodynamic activity is very wide. Spectral lines were
measured from acoustic to visible range. Pelling et al.50,51 measured mechanical membrane os-
cillations by AFM (atomic force microscope) at 1.63 and 0.87 kHz at the temperature of 30 and
22◦C, respectively. Mechanical and electrical oscillations in the acoustic band were confirmed by
Jel´
ınek et al.52 Pohl8assessed the frequency of oscillations from the dielectrophoretic atraction of
dielectric particles in the range 5 kHz–1 MHz. Kirson et al.15,16 described disturbances of internal
cellular electrodynamic field and consequently also polymerization of the microtubules in the M
phase by external electromagnetic field in the frequency range 100–300 kHz. H¨
olzel and Lamprecht9
and H¨
olzel10 measured electrodynamic activity of yeast cells and alga cells in the frequency range
1.5–52 MHz. Pokorn´
yet al.13 observed and evaluated electrodynamic field generated by yeast cells
in the frequency band 8–9 MHz. The measured activity was associated with mitosis. The high
activity coincides with the rearrangement of the microtubules into a mitotic spindle, with binding
of chromatids to kinetochore microtubules, and with the elongation of the mitotic spindle during
anaphase A and B. Vedruccio and Meessen17 disclosed interaction of the electromagnetic field with
cancer tissue at 465 MHz and the first and the second harmonic component corresponding to reso-
nant interaction. Albrecht-Buehler53–55 proved the ability of cells to detect electromagnetic signals
of other cells in the red and near-infrared range. The cells are able to sense the radiation and to
determine the direction to the source.
Measurement of microtubules in vitro was performed by Sahu et al.14 but the results have not
been published as yet. The individual microtubules were polymerized in the oscillating electric field.
Sahu et al.14 describes ballistic conductance of electrons moving along spiral orbits with different
steepness and several resonant frequencies in the microtubules around 10 MHz.
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FIG. 2. Physical aspects of biological activity – physical mechanisms depend on mitochondrial function. Mitochondrial
transport of protons into cytosol leads to generation of a strong static electric field and a high level of water ordering. As
a consequence damping of oscillations in microtubules is low. Microtubule oscillations may be highly excited by energy
supply, in particular by liberation of the non-utilized energy (“wasted” energy) from mitochondria.
The electrodynamic field measured at living cells is assumed to be generated by fundamen-
tally non-linear elasto-electrical oscillations of microtubules. The oscillations may display several
resonant frequencies as follows from AFM measurements in the acoustic region and interaction of
external electromagnetic fields with living cells, in particular in the 0.1–0.3 MHz and 465 MHz
regions. A direct measurement of coherent resonant signals using special nanotechnological sys-
tems at physiological temperature may disclose essential spectral properties of microtubules, their
structures and cells.
V. PHYSICAL PROCESSES IN CELLS
The interplay of mitochondria with microtubules may form an essential basis for physical pro-
cesses in cells. A decisive factor for adjusting non-linear properties of microtubules and formation
of ordered cytosol water might be the static electric field created around mitochondria. Non-linear
properties make possible transformation of random excitation into coherent oscillations in micro-
tubules. Ordered water is a quasi-elastic medium providing low damping of microtubule oscillations.
Non-utilized energy efflux from mitochondria supplies energy exciting oscillations, shifts the sys-
tem far from thermodynamic equilibrium, and establishes the coherent state. Electrodynamic field
generated by microtubules may play a significant role in biological activity. The electric oscillating
field might produce a traction force (predicted by Frauenfelder et al.56) for directed transport of
material, morphological force for organization of cellular structures, interaction force for intra and
inter-cellular purposes (Pokorn´
y,20,21 Pokorn´
yet al.22), and may serve as a medium for information
transfer. A schematic picture of physical links in cellular activity is given in Fig. 2(Pokorn´
yet al.18).
VI. CANCER DISTURBANCES
Suppression of oxidative metabolism is a general feature of cancer cells. One type of the Warburg
effect is shown in Fig. 3. Cancer process inhibits oxidative energy production of ATP and GTP that
may be caused by diminished proton transfer across the inner mitochondrial membrane. Warburg
assessed ratio of the amount of energy produced by the fermentation and the oxidation (respiration)
process in healthy and cancer cells. In healthy cells the oxidation energy production may be even 100
times greater than the fermentation one (for instance in kidney and liver cells). With the exception
of the cancer cells with reversed Warburg effect (Pavlides et al.57) fermentative production in cancer
cells is bigger than in healthy cells. In the cancer cell fermentation may participate in energy
production approximately by 1/3–2/3 part of the total output and the average value may be of about
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FIG. 3. A schematic picture of glycolytic phenotype of cancer cells (Bonnet et al.68). The pyruvate pathway is blocked
by cancer PDK (pyruvate dehydrogenase kinase). PDH (pyruvate dehydrogenase) enzymes in the mitochondrial matrix
phosphorylated by PDK are dysfunctional and pyruvate is not broken down into the two-carbon acetyl group on acetyl
CoA (Coenzyme). Only about one half of protons is transferred into the intermembrane space than in fully functional
mitochondrion. But similar effect of the proton transfer inhibition may be caused by other defects in the Krebs cycle.
one half (Warburg1,2). If the cancer and the healthy cells have the same amount of the total energy
and the same mitochondrial efficiency of utilization of the electrochemical proton gradient (by ATP
synthase protein complexes) then only about one half of protons are transported across the inner
membrane in comparison with a “healthy” mitochondrion. The non-utilized energy liberated from
mitochondria is correspondingly lowered too. The static electric field is weaker and ordering level
of water diminished. Damping of oscillations in microtubules is increased, excitation lowered, and
non-linear properties shifted towards linear region. Power and coherence of the electrodynamic field
are diminished. Coherent processes in the cell are disturbed, and the random ones play a more
important role (Pokorn´
yet al.,18,19 Pokorn´
y23). Mitochondria are the boundary entities between
chemical-genetic and physical processes.
Mitochondrial dysfunction may develop in the period before appearance of malignant properties.
In the cervical cancer mitochondrial dysfunction turn was assessed in the period from precancerous
to cancer cells (Jandov´
aet al.58). Therefore, the disturbances of the electromagnetic activity in cancer
cells might be responsible for malignant properties. Interaction forces between healthy cells may be
greater than those between cancer cells. The healthy cell may pull the cancer cell into healthy tissue.
This mechanism may be responsible for local invasion (Pokorn ´
y59). The metastatic phase starts with
disorganization of the cytoskeleton (Beil et al.,60 Suresh et al.,61 Suresh62). After disturbances of the
cytoskeleton the frequency spectrum and the spatial pattern of the generated electrodynamic field
may be altered to such extent that the cancer cell loses connection with the surrounding cells in the
tissue, can leave the tissue, move freely in the body, and form a metastatic nodule even in distant
organs.
VII. DISCUSSION
Warburg effect (Warburg et al.1) disclosed nearly ninety years ago had been accepted as a
secondary side effect for a long time. This point of view was revisited in the last decade and
analysis of the mitochondrial dysfunction and its treatment is an urgent issue now. Warburg effect is
one of the most important links along the cancer transformation pathway. But consequences of the
mitochondrial dysfunction were not elucidated. The Fr¨
ohlich’s hypothesis makes possible to analyze
consequent disturbance. Nevertheless, Fr¨
ohlich’s hypothetical prediction of coherent electrodynamic
activity of living systems was classified as impossible due to strong viscosity damping by water
(Foster and Baisch63) or generally low quality factor of biological oscillators (Reimers et al.64
and Mc Kemmish et al.65). Above it, their analysis is based on replacement of the essentially
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non-linear Fr¨
ohlich’s system by a linear one (they neglected non-linear interactions between elastic
and polarization fields). Experimental data on water ordering and measurement on microtubules
prove and strongly support the Fr¨
ohlich’s idea of electrodynamic activity of biological systems.
Mitochondrial function conditions physical processes in living cells. Mitochondria are unique
organelles in the cell. Mitochondrial function is regulated by chemical messengers. But besides
triggering the apoptosis by chemical means mitochondrial main role is not in chemical region.
Mitochondria are the boundary organelles accepting chemical signals and building conditions for
physical processes. Mitochondrial malfunction degrades physical processes in cells. Physical links
along the cancer transformation pathway should be studied and specified.
There are several important directions for the future research. Experimental research of in vivo
and in vitro electrodynamic fields of living cells or cellular structures (for instance microtubules)
is possible due to development of nanotechnology. The total turnover of power of a cell may be of
the order of magnitude about 10-13 W. This value of the turnover of power was measured on yeast
cells (Lamprecht66). A similar amount of power may be supplied for excitation of electrodynamic
oscillations (for instance, non utilized energy liberated from mitochondria). Taking into account
efficiency of conversion of random supply to coherent oscillations, number of microtubules in the
cell and power distribution in particular frequency spectral lines, the power exciting individual
microtubule spectral line may be of about 10-17 W. For a high quality factor the maximum power
stored in the oscillating microtubule may be of about 10-15 W. But the measurement system may
significantly damp the oscillation system and change its frequency spectrum. The electrodynamic
oscillations may be measured at a patch of linear dimension smaller than about 1 μm corresponding
to the microtubule binding spot at the inner side of the membrane (Kuˇ
cera et al.67). Measurement
should be performed at the physiological temperature of living cells. In vitro measurements of
microtubules should disclose parameters for assessment of their electrodynamic characteristics.
Theoretical research should explain the main conditions for water ordering around mitochon-
dria and its characteristic properties, generation of coherent electrodynamic field by microtubules,
interaction in the biological system through the electrodynamic field, creation of a general quan-
tum theory of coherence in biological systems, and–very likely–development of a novel non-linear
quantum (electrodynamic dynamic field) theory for biological systems.
Important point concerns convergence of classical biology and biochemistry with a novel
biological physics. Further research should bridge a gap between the chemical and genetic processes
on the one hand and physical ones on the other hand. Understanding of biological activity and
cancer transformation pathway requires conversion of both parts. Biochemical, genetic, and physical
mechanisms are mutually dependent and equally important. A more sophisticated model of biological
activity should be built.
Important part of cancer transformation is a special case of physical processes in living cells and
their theoretical and experimental investigation. Mitochondrial dysfunction featured by decreased
proton pumping from the matrix space results in fundamentally disturbed electrodynamic field in
cancer cells (Pokorn´
yet al.18). Diminished power and coherence of the electrodynamic field may
be the most pronounced difference between the healthy and the cancer cells in the clinical phase.
Therefore, mitochondria and physical processes should be targeted for cancer treatment. The standard
therapeutic strategy is based on cancer cell killing. But such treatment may also damage healthy
cells and limits its further application to treatment of recurrent tumors. The therapeutic strategy
may be first of all based on restoration of normal cell function. For instance, opening the pyruvate
pathway in mitochondria by inhibition the PDK restores mitochondrial normal function and unlocks
the apoptotic pathway. The physical processes in the cell and the cell itself are reversed to normal
operation. Consequently, if the cell system is damaged too much then apoptosis is triggered. Targeting
mitochondria acts in the region of the main differences between healthy and cancer cells.
VIII. CONCLUSIONS
Cooperation of mitochondria and microtubules is a unique phenomenon in living cells.
Mitochondria are multifunctional organelles controlled by chemical and genetic signals and provid-
ing conditions for physical mechanisms. Mitochondria pump protons across the inner membrane,
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produce ATP and GTP, and liberate the non-utilized energy. Protons pumped from the matrix space
cause water ordering, formation of the zone of a strong static electric field in the cytosol, and the
proton space charge layer.
Microtubules may generate electrodynamic field providing fundamental biological functions.
The strong electric field conditions non-linear interactions. Damping of microtubule oscillations by
organized water is very low. Liberation of non-utilized energy from mitochondria supplies energy
for oscillation.
Mitochondria dysfunction in cancer cells may cause increased damping of microtubule oscil-
lations, diminished energy supply, and shift the non-linear properties towards linear region. Power
and coherence of the generated electrodynamic field is diminished.
ACKNOWLEDGMENTS
The research results presented in this paper were supported by the grant No. 102/11/0649 of the
Czech Science Foundation GA CR.
1O. Warburg, K. Posener, and E. Negelein, “ ¨
Uber den Stoffwechsel der Carcinomzelle,” Biochem. Z. 152, 309 (1924).
2O. Warburg, “On the Origin of Cancer Cells,” Science 123, 309 (1956).
3H. Fr¨
ohlich, “Quantum Mechanical Concepts in Biology,” in Theoretical Physics and Biology, 1st Int. Conf. Theor. Phys.
Biol., Versailles, edited by M. Marois (North Holland, Amsterdam, 13, 1969).
4H. Fr¨
ohlich, “Bose Condensation of Strongly Excited Longitudinal Electric Modes,” Phys. Lett. A 26, 402 (1968).
5H. Fr¨
ohlich, “Collective Behaviour of Non-Linearly Coupled Oscillating Fields (with Applications to Biological Systems),”
J. Collective Phenom. 1, 101 (1973).
6H. Fr¨
ohlich, “The Biological Effects of Microwaves and Related Questions,” In Advances Electronics Electron. Phys. 53,
85 (1980).
7H. Haken, “Cooperative phenomena in systems far from thermal equilibrium and in nonphysical systems,” Rev. Modern
Phys. 47, 67 (1975).
8H. A. Pohl, “Oscillating Fields about Growing Cells,” Int. J. Quant. Chem. Quant. Biol. Symp. 7, 411 (1980).
9R. H¨
olzel and I. Lamprecht, “Electromagnetic Fields around Biological Cells,” Neural Net. World 4, 327 (1994).
10 R. H¨
olzel, “Electric Activity of Non-Excitable Biological Cells at Radio Frequencies,” Electro- and Magnetobiol. 20,1
(2001).
11 J. Pokorn´
y, F. Jel´
ınek, V. Trkal, I. Lamprecht, and R. H¨
olzel, “Vibrations in Microtubules,” J. Biol. Phys. 23, 171 (1997).
12 J. Pokorn´
y, F. Jel´
ınek, and V. Trkal, “Electric field around microtubules,” Bioelectrochem. Bioenergetics 45, 239 (1998).
13 J. Pokorn´
y, J. Haˇ
sek, F. Jel´
ınek, J. ˇ
Saroch, and B. Pal´
an, “Electromagnetic Activity of Yeast Cells in the M Phase,” Electro-
Magnetobiol. 20, 371 (2001).
14 S. Sahu, S. Ghosh, K. Hirata, D. Fujita, and A. Bandyopadhyay, “Ultra-fast condensation of tubulins into microtubule
unravels a generic resonance engineering,” (personal communication).
15 E. D. Kirson, Z. Gurvich, R. Schneiderman, E. Dekel, A. Itzhaki, Y. Wasserman, R. Schatzberger, and Y. Palti, “Disruption
of Cancer Cell Replication by Alternating Electric Fields,” Cancer Res. 64, 3288 (2004).
16 E. D. Kirson, V. Dbal ´
y, F.Tovaryˇ
s, J. Vymazal, J. F.Soustiel, A. Itzhaki, D. Mordechovich, S. Steinberg-Shapira, Z. Gurvich,
R. Schneiderman, Y. Wasserman, M. Salzberg, B. Ryffel, D. Goldsher, E. Dekel, and Y. Palti, “Alternating electric fields
arrest cell proliferation in animal tumor models and human brain tumors,” PNAS 104, 10152 (2007).
17 C. Vedruccio and A. Meessen, “EM Cancer Detection by Means of Non-Linear Resonance Interaction,” in Proceedings
PIERS, Progress in Electromagnetics Research Symposium, Pisa, Italy, March 28–31 2004, 909 (2004).
18 J. Pokorn´
y, C. Vedruccio, M. Cifra, and O. Kuˇ
cera, “Cancer physics: diagnostics based on damped cellular elastoelectrical
vibrations in microtubules,” Eur. Biophys. J. 40, 747 (2011).
19 J. Pokorn´
y, J. Haˇ
sek, J. Vaniˇ
s, and F. Jel´
ınek, “Biophysical aspects of cancer – electromagnetic mechanism,” Indian J.
Exper. Biol. 46, 310 (2008).
20 J. Pokorn´
y, “Endogenous Electromagnetic Forces in Living Cells: Implications for Transfer of Reaction Components,”
Electro- Magnetobiol. 20, 59 (2001).
21 J. Pokorn´
y, “Excitation of vibration in microtubules in living cell,” Bioelectrochem. 63, 321 (2004).
22 J. Pokorn´
y, J. Haˇ
sek, and F. Jel´
ınek, “Electromagnetic Field in Microtubules: Effects on Transfer of Mass Particles and
Electrons,” J. Biol. Phys. 31, 501 (2005).
23 J. Pokorn´
y, “Biophysical Cancer Transformation Pathway,” Electromagn. Biol. Med. 28, 105 (2009).
24 J. Pokorn´
y, “Fr¨
ohlich’s Coherent Vibrations in Healthy and Cancer Cells,” Neural Netw. World 19, 369 (2009).
25 R. Damadian, “Tumor detection by nuclear magnetic resonance,” Science 171, 1151 (1971).
26 L. A. Amos, “Structure of Microtubules,” in Microtubules, edited by K. Roberts and J. S. Hyams (Academic Press,
London–New York, 1, 1979).
27 H. Stebbings and C. Hunt, “The nature of the clear zone around microtubules,” Cell Tissue Res. 227, 609 (1982).
28 G. Ling, “A new theoretical foundation for the polarized-oriented multilayer theory of cell water and for inanimate systems
demonstrating long-range dynamic structuring of water molecules,” Physiol. Chem. Phys. Med. NMR 35, 91 (2006).
29 J. Zheng and G. H. Pollack, “Long-range forces extending from polymer-gel surfaces,” Phys.Rev.E68, 031408–1 (2003).
011207-10 Jiˇ
r´
ı Pokorn´
y AIP Advances 2, 011207 (2012)
30 J. Zheng, W.Chin, E. Khijniak, E. Khijniak, Jr., and G. H. Pollack, “Surfaces and interfacial water: evidence that hydrophilic
surfaces have long-range impact,” Advanc. colloid interface sci. 127, 19 (2006).
31 G. Pollack, I. Cameron, and D. Wheatley, Water and the Cell (Springer, Dodrecht, 2006).
32 B. Chai, H. Yoo, and G. H. Pollack, “Effect of radiant energy on near-surface water,” J. Phys. Chem. B 113, 13953 (2009).
33 B. Chai, J. Zheng, Q. Zhao, and G. H. Pollack, “Spectroscopic studies of solutes in aqueous solution,” J. Phys. Chem. A
112, 2242 (2008).
34 S. Zimmerman, A. M. Zimmerman, G. D. Fullerton, R. F. Luduena, and I. L. Cameron, “Water Ordering during the Cell
Cycle: Nuclear Magnetic Resonance Studies of the Sea-Urchin Egg,” J. Cell Sci. 79, 247 (1985).
35 E. C. Fuchs, J. Woisetschl¨
ager, K. Gatterer, E. Maier, R. Pecnik, and H. Eisenk¨
olbl, “The floating water bridge,” J. Phys.
D: Appl. Phys. 40, 6112 (2007).
36 E. C. Fuchs, K. Gatterer, G. Holler, and J. Woisetschl¨
ager, “Dynamics of the floating water bridge,” J. Phys. D: Appl.
Phys. 41, 185502–1 (2008).
37 E. C. Fuchs, B. Bitschnau, J. Woisetschl¨
ager, E. Maier, B. Beuneu, and J. Teixeira, “Neutron scattering of a floating heavy
water bridge,” J. Phys. D: Appl. Phys. 42, 065502–1 (2009).
38 L. Giuliani, E. D’Emilia, A. Lisi, S. Grimaldi, A. Foletti, and E. Del Giudice, “The Floating Water Bridge under Strong
Electric Potential,” Neural Netw. World 19, 393 (2009).
39 G. Preparata, QED Coherence in Matter (World Scientific, New Jersey, London, Hong Kong, 1995).
40 E. Del Giudice, V. Elia, and A. Tedeschi, “The role of water in the living organisms,” Neural Netw. World 19, 355 (2009).
41 E. Del Giudice and A. Tedeschi, “Water and Autocatalysis in Living Matter,” Electromagn. Biol. Med. 28, 46 (2009).
42 K. M. Tyner, R. Kopelman, and M. A. Philbert, “‘Nanosized Voltmeter’ Enables Cellular-Wide Electric Field Mapping,”
Biophys. J. 93, 1163 (2007).
43 R. Tilbury and T. Quickenden, “Luminescence from the yeast Candida utilis and comparisons across three genera,” J.
Biolum. Chemilum. 7, 245 (1992).
44 A. P. Batyanov, “Distant Optical Interaction of the Mitochondria through Quartz,” Byuleten Exper. Biol. Med. 97, 675
(1984).
45 A. P. Batyanov, “Correlation between Mitochondria Metabolism and the Physical Characteristics of Incubation Cells,” In
Biophotonics. Non-equilibrium and Coherent Systems in Biology, Biophysics and Biotechnology, edited by L. Belousov,
and F.-A. Popp, (Bioinform Services Co, Moscow, 439, 1995).
46 M. Satari´
c, J. A. Tuszy´
nski, and R. B. ˇ
Zakula, “Kinklike Excitations as an Energy Transfer Mechanism in Microtubules,”
Phys. Rev. E 48, 589 (1993).
47 J. A. Tuszy´
nski, S. Hameroff, M. Satari´
c, B. Trpisova, and M. L. A. Nip, “Ferroelectric Behavior in Microtubule Dipole
Lattices: Implications for Information Processing, Signaling and Assembly/Disassembly,” J. theor. Biol. 174, 371 (1995).
48 R. Stracke, K. J. B¨
ohm, L. Wollweber, J. A. Tuszy ´
nski, and E. Unger, “Analysis of the Migration of Single Microtubules
in Electric Fields,” Biochem. Biophys. Res. Comm. 293, 602 (2002).
49 A. E. Pelling, D. W. Dawson, D. M. Carreon, J. J. Christiansen, R. R. Shen, M. A. Teitell, and J. K. Gimzewski, Distinct
contributions of microtubule subtypes to cell membrane shape and stability, “Distinct contributions of microtubule subtypes
to cell membrane shape and stability,” Nanomed.: Nanotechnol. Biol. Med. 3, 43 (2007).
50 A. E. Pelling, S. Sehati, E. B. Gralla, J. S. Valentine, and J. K. Gimzewski, “Local Nano-mechanical Motion of the Cell
Wall of Saccharomyces cerevisiae,” Science 305, 1147 (2004).
51 A. E. Pelling, S. Sehati, E. B. Gralla, and J. K. Gimzewski, “Time dependence of the frequency and amplitude of the local
nanomechanical motion of yeast,” Nanomed.: Nanotechnol. Biol. Med. 1, 178 (2005).
52 F. Je l ´
ınek,M.Cifra,J.Pokorn
´
y, J. Vaniˇ
s, J. ˇ
Simˇ
sa,J.Ha
ˇ
sek, and I. Fr´
ydlov´
a, “Measurement of Electrical Oscillations and
Mechanical Vibrations of Yeast Cells Membrane around 1 kHz,” Electromag. Biol. Med. 28, 223 (2009).
53 G. Albrecht–Buehler, “Rudimentary Form of Cellular ‘Vision’,” Proc. Natl. Acad. Sci. USA 89, 8288 (1992).
54 G. Albrecht–Buehler, “Surface Extensions of 3T3 Cells towards Distant Infrared Light Sources,” J. Cell. Biol. 114, 493
(1991).
55 G. Albrecht–Buehler, “A long-range attraction between aggregating 3T3 cells mediated by near-infrared light scattering,”
PNAS 102, 5050 (2005).
56 H. Frauenfelder, P. G. Volynes, and R. H. Austin, “Biological Physics,” Mod. Phys. 71, S419 (1999).
57 S. Pavlides, D. Whitaker–Menezes, R. Castello–Cros, N. Flomenberg, A. K. Witkiewicz, P. G. Frank, M. C. Casimiro,
Ch. Wang, P. Fortina, S. Addya, R. G. Pestell, U. E. Martinez-Outschoorn, F. Sotgia, and M. P. Lisanti, “The reverse
Wartburg effect: aerobic glycolysis in cancer associated fibroblast and the tumor stroma,” Cell Cycle 8, 3984 (2009).
58 A. Jandov´
a, J. Pokorn´
y, J. Kobilkov´
a, M. Janouˇ
sek, J. Maˇ
sata, S. Trojan, M. Nedbalov´
a, A. Dohnalov´
a, A. Bekov´
a,
V. S l a v ´
ık, A. ˇ
Coˇ
cek, and J. Sanitr´
ak, “Cell-Mediated Immunity in Cervical Cancer Evolution,” Electromagn. Biol. Med.
28, 1 (2009).
59 J. Pokorn´
y, “The Role of Fr¨
ohlich’s Coherent Excitations in Cancer Transformation of Cells,” In Herbert Fr ¨
ohlich, FRS: A
physicist ahead of his time, edited by G. J. Hyland, and P. Rowlands (The University of Liverpool, Liverpool, 177, 2006).
60 M. Beil, A. Micoulet, G. von Wichert, S. Paschke, P. Walther, M. B. Omary, P. P. Van Veldhoven, U. Gern, E. Wolff-Hieber,
J. Eggermann, J. Waltenberger, G. Adler, J. Spatz, and T. Seufferlein, “Sphingosylphosphorylcholine regulates keratin
network architecture and visco-elastic properties of human cancer cells,” Nature Cell Biol. 5, 803 (2003).
61 S. Suresh, J. Spatz, J. P. Mills, A. Micoulet, M. Dao, C. T. Lim, M. Beil, and T. Seufferlein, “Connections between
single-cell biomechanics and human disease states: gastrointestinal cancer and malaria,” Acta Biomaterialia 1, 15 (2005).
62 S. Suresh, “Biomechanics and biophysics of cancer cells,” Acta Materialia 55, 3989 (2007).
63 K. R. Foster and J. W. Baisch, “Viscous damping of vibrations in microtubules,” J. Biol. Phys. 26, 255 (2000).
64 J. R. Reimers, L. K. McKemmish, R. H. McKenzie, A. E. Mark, and N. S. Hush, “Weak, strong, and coherent regimes of
Fr¨
ohlich condensation and their applications to terahertz medicine and quantum consciousness,” PNAS 106, 4219 (2009).
65 L. K. McKemmish, J. R. Reimers, R. H. McKenzie, A. E. Mark, and N. S. Hush, “Penrose–Hameroff orchestrated
objective-reduction proposal for human consciousness is not biologically feasible,” Phys. Rev. E 80, 021912–1 (2009).
011207-11 Jiˇ
r´
ı Pokorn´
y AIP Advances 2, 011207 (2012)
66 I. Lamprecht, “Growth and metabolism in yeasts,” In Biological Microcalorimetry, edited by A. E. Beezer (Academic
Press, London, 43-112 (1980).
67 O. Kuˇ
cera, M. Cifra, and J. Pokorn´
y, “Technical aspects of measurement of cellular electromagnetic field,” Eur. Biophys.
J. 39, 1465 (2010).
68 S. Bonnet, S. L. Archer, J. Allalunis-Turner, A. Haromy, Ch. Beaulieu, R. Thompson, Ch. T. Lee, G. D. Lopaschuk,
L. Puttagunta, S. Bonnet, G. Harry, K. Hashimoto, Ch. J. Porter, M. A. Andrade, B. Thebaud, and E. D. Michelakis, “A
Mitochondria-K+Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer
Growth,” Cancer Cell 11, 37 (2007).
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