Hypothesis of coherent vibration states in biological systems based on nonlinear interaction between longitudinal elastic and electric polarization fields with metabolic energy supply was formulated by Frohlich. Conditions for excitation of coherent states and generation of electromagnetic fields are satisfied in microtubules which form electrical polar structures. Numerical models are used for analysis of Frohlich's vibration states in cells. Reduction of activity and of energy production in mitochondria, and disintegration of cytoskeleton structures by phosphorylation on the pathway of cancer trasformation can diminish excitation of the Frohlich's vibration states and of the generated electromagnetic field, which results in disturbances of the interaction forces between cells. Interaction forces between cancer cells may be smaller than interaction forces between healthy cells and cancer cells as follows from numerical models. Mechanism of malignity, i.e. local invasion, detachment of cancer cells, and metastasis, is assumed to depend on the electromagnetic field.

• MeSH
• biofyzika metody   MeSH
• biologické modely MeSH
• buňky 3T3 MeSH
• cytoskelet metabolismus   MeSH
• elektromagnetická pole MeSH
• elektromagnetické jevy MeSH
• lidé MeSH
• mikroskopie atomárních sil MeSH
• mikrotubuly metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• myši MeSH
• nádory metabolismus   MeSH
• pružnost MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Microtubules are electrically polar structures fulfilling prerequisites for generation of oscillatory electric field in the kHz to GHz region. Energy supply for excitation of elasto-electrical vibrations in microtubules may be provided from GTP-hydrolysis; motor protein-microtubule interactions; and energy efflux from mitochondria. We calculated electric field generated by axial longitudinal vibration modes of microtubules for random, and coherent excitation. In case of coherent excitation of vibrations, the electric field intensity is highest at the end of microtubule. The dielectrophoretic force exerted by electric field on the surrounding molecules will influence the kinetics of microtubule polymerization via change in the probability of the transport of charge and mass particles. The electric field generated by vibrations of electrically polar cellular structures is expected to play an important role in biological self-organization.

• MeSH
• biologické hodiny fyziologie   MeSH
• elektromagnetická pole MeSH
• eukaryotické buňky fyziologie   MeSH
• mikrotubuly fyziologie   MeSH
• náhodné rozdělení MeSH
• polarita buněk fyziologie   MeSH
• sušené kvasnice MeSH
• vibrace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

A framework of postulates is formulated to define the existence, nature, and function of a coherent state far from thermodynamic equilibrium in biological systems as an essential condition for the existence of life. This state is excited and sustained by energy supply. Mitochondria producing small packets of energy in the form of adenosine and guanosine triphosphate and strong static electric field around them form boundary elements between biochemical-genetic and physical processes. The transformation mechanism of chemical energy into useful work for biological needs and the excitation of the coherent state far from thermodynamic equilibrium are fundamental problems. The exceptional electrical polarity of biological objects and long-range interactions suggest a basic role of the endogenous electromagnetic field generated by living cells. The formulated postulates encompass generation, properties and function of the electromagnetic field connected with biological activity and its pathological deviations. Excited longitudinal polar oscillations in microtubules in eukaryotic cells generate the endogenous electromagnetic field. The metabolic activity of mitochondria connected with water ordering forms conditions for excitation. The electrodynamic field plays an important role in the establishment of coherence, directional transport, organization of morphological structures, interactions, information transfer, and brain activity. An overview of experimental results and physical models supporting the postulates is included. The existence of the endogenous biological electromagnetic field, its generation by microtubules and supporting effects produced by mitochondria have a reasonable experimental foundation. Cancer transformation is a pathological reduction of the coherent energy state far from thermodynamic equilibrium. Malignancy, i.e. local invasion and metastasis, is a direct consequence of mitochondrial dysfunction, disturbed microtubule polar oscillations and the generated electromagnetic field.

• MeSH
• biologické modely * MeSH
• elektromagnetická pole * MeSH
• energetický metabolismus fyziologie   MeSH
• lidé MeSH
• mikrotubuly metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• nádorová transformace buněk * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Microtubules are important structures in the cytoskeleton, which organizes the cell. Since microtubules are electrically polar, certain microtubule normal vibration modes efficiently generate oscillating electric field. This oscillating field may be important for the intracellular organization and intercellular interaction. There are experiments which indicate electrodynamic activity of variety of cells in the frequency region from kHz to GHz, expecting the microtubules to be the source of this activity. In this paper, results from the calculation of intensity of electric field and of radiated electromagnetic power from the whole cellular microtubule network are presented. The subunits of microtubule (tubulin heterodimers) are approximated by elementary electric dipoles. Mechanical oscillation of microtubule is represented by the spatial function which modulates the dipole moment of subunits. The field around oscillating microtubules is calculated as a vector superposition of contributions from all modulated elementary electric dipoles which comprise the cellular microtubule network. The electromagnetic radiation and field characteristics of the whole cellular microtubule network have not been theoretically analyzed before. For the perspective experimental studies, the results indicate that macroscopic detection system (antenna) is not suitable for measurement of cellular electrodynamic activity in the radiofrequency region since the radiation rate from single cells is very low (lower than 10⁻²⁰ W). Low noise nanoscopic detection methods with high spatial resolution which enable measurement in the cell vicinity are desirable in order to measure cellular electrodynamic activity reliably.

• MeSH
• biologické hodiny fyziologie   MeSH
• biologické modely MeSH
• buněčná membrána fyziologie   MeSH
• centrozom fyziologie   MeSH
• elektromagnetická pole MeSH
• membránové potenciály fyziologie   MeSH
• mikrotubuly fyziologie   MeSH
• polarita buněk fyziologie   MeSH
• vibrace MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells--a strategy used in novel methods for cancer treatment.

• MeSH
• akustika MeSH
• aparát dělícího vřeténka fyziologie   MeSH
• biologické modely * MeSH
• elektromagnetické jevy MeSH
• lidé MeSH
• mikrotubuly fyziologie   MeSH
• mitóza MeSH
• počítačová simulace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules. We are extending this prior hypothesis of the endogenous electromagnetic field in the cell postulating that polarized centriole in immune and viral synapse could serve as a monopole antenna. This is an addition to our hypothesis that primary cilium could serve as a monopole antenna. We simulated the distribution of electric field of centriole of polarized centrosome as a monopole antenna in immune and viral synapse. Very weak electromagnetic field of polarized centriole of CD8+ T lymphocyte in IS can contribute to the transport of cytolytic granules into the attacked (cancer) cell. Analogically, very weak electromagnetic field of polarized centriole in viral synapse of infected CD4 cells can aid the transport of viruses (human immunodeficiency virus) to non-infected CD4 cells. We hypothesized that healthy organisms need these monopole antennas. If, during the neoplastic transformation, healthy cells lose monopole antennas in form of primary cilia, the IS aims to replace them by monopole antennas of polarized centrioles in IS to restore homeostasis.

• MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• centrioly genetika   MeSH
• centrozom imunologie   MeSH
• elektromagnetická pole MeSH
• imunitní systém * MeSH
• lidé MeSH
• mikrotubuly genetika   metabolismus   MeSH
• nádory genetika   imunologie   patologie   MeSH
• polarita buněk genetika   imunologie   MeSH
• synapse genetika   virologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Coherent vibration states in biological systems excited in nonlinear electrically polar structures by metabolic energy supply were postulated by H. Frohlich. Frohlich's requirements for coherent vibrations and generation of electromagnetic field are satisfied by microtubules whose subunits are electric dipoles. Static electric field around mitochondria and "wasted energy" efflux from them provide nonlinear conditions and coherent excitation. Numerical models are used for analysis of coherent vibration states. A hypothesis is presented that dysfunction of mitochondria (i.e., extinction of the zones of the static electric field and of the efflux of "wasted energy") and disintegration of the cytoskeleton on the pathway of cancer transformation result in disturbances of coherence of the cellular electrically polar oscillations and of the generated electromagnetic field with consequences in cellular organization and interactions between cells. Local invasion, detachment, and metastasis of cancer cells are subsequent events of disturbed electromagnetic interactions.

• MeSH
• biofyzikální jevy MeSH
• biologické modely MeSH
• cytoskelet metabolismus   účinky záření   MeSH
• elektromagnetická pole škodlivé účinky   MeSH
• lidé MeSH
• mitochondrie metabolismus   účinky záření   MeSH
• nádorová transformace buněk MeSH
• nádorové buněčné linie MeSH
• nádory patologie   MeSH
• nelineární dynamika MeSH
• vibrace MeSH
• Check Tag
• lidé MeSH

Biological systems are hierarchically self-organized complex structures characterized by nonlinear interactions. Biochemical energy is transformed into work of physical forces required for various biological functions. We postulate that energy transduction depends on endogenous electrodynamic fields generated by microtubules. Microtubules and mitochondria colocalize in cells with microtubules providing tracks for mitochondrial movement. Besides energy transformation, mitochondria form a spatially distributed proton charge layer and a resultant strong static electric field, which causes water ordering in the surrounding cytosol. These effects create conditions for generation of coherent electrodynamic field. The metabolic energy transduction pathways are strongly affected in cancers. Mitochondrial dysfunction in cancer cells (Warburg effect) or in fibroblasts associated with cancer cells (reverse Warburg effect) results in decreased or increased power of the generated electromagnetic field, respectively, and shifted and rebuilt frequency spectra. Disturbed electrodynamic interaction forces between cancer and healthy cells may favor local invasion and metastasis. A therapeutic strategy of targeting dysfunctional mitochondria for restoration of their physiological functions makes it possible to switch on the natural apoptotic pathway blocked in cancer transformed cells. Experience with dichloroacetate in cancer treatment and reestablishment of the healthy state may help in the development of novel effective drugs aimed at the mitochondrial function.

• MeSH
• biologické modely * MeSH
• elektromagnetická pole * MeSH
• lidé MeSH
• mitochondrie účinky záření   MeSH
• nádorová transformace buněk účinky záření   MeSH
• nádory patofyziologie   MeSH
• přenos energie * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Physical processes in living cells were not taken into consideration among the essentials of biological activity, regardless of the fact that they establish a state far from thermodynamic equilibrium. In biological system chemical energy is transformed into the work of physical forces for various biological functions. The energy transformation pathway is very likely connected with generation of the endogenous electrodynamic field as suggested by experimentally proved electrodynamic activity of biological systems connected with mitochondrial and microtubule functions. Besides production of ATP and GTP (adenosine and guanosine triphosphate) mitochondria form a proton space charge layer,

• MeSH
• adenosintrifosfát metabolismus   MeSH
• apoptóza fyziologie   genetika   imunologie   MeSH
• biomedicínský výzkum metody   trendy   MeSH
• elektromagnetická pole škodlivé účinky   MeSH
• financování organizované MeSH
• fyziologie buňky fyziologie   genetika   imunologie   MeSH
• glykolýza fyziologie   genetika   imunologie   MeSH
• guanosintrifosfát metabolismus   MeSH
• kyselina dichloroctová aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• mikrotubuly fyziologie   metabolismus   patologie   MeSH
• mitochondrie fyziologie   metabolismus   patologie   MeSH
• nádorová transformace buněk genetika   imunologie   účinky léků   MeSH
• nádory etiologie   metabolismus   terapie   MeSH
• Check Tag
• lidé MeSH

Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules' ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg) effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells), and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts), disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH