The general mechanism of controlling, information and organization in biological systems is based on the internal coherent electromagnetic field. The electromagnetic field is supposed to be generated by microtubules composed of identical tubulin heterodimers with periodic organization and containing electric dipoles. We used a classical dipole theory of generation of the electromagnetic field to analyze the space-time coherence. The structure of microtubules with the helical and axial periodicity enables the interaction of the field in time shifted by one or more periods of oscillation and generation of coherent signals. Inner cavity excitation should provide equal energy distribution in a microtubule. The supplied energy coherently excites oscillators with a high electrical quality, microtubule inner cavity, and electrons at molecular orbitals and in 'semiconduction' and 'conduction' bands. The suggested mechanism is supposed to be a general phenomenon for a large group of helical systems.

• Klíčová slova
• helical and axial periodicity, ionization, microtubules, near-field dipole theory, oscillation cavity, water potential layer,
• MeSH
• elektromagnetická pole * MeSH
• mikrotubuly chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if electric pulses within biomedically-attainable parameters could directly influence intra-cellular components such as cytoskeletal proteins. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields. To help clarify this question, we first identified that a tubulin heterodimer is a natural biological target for intense electric fields due to its exceptional electric properties and crucial roles played in cell division. Using molecular dynamics simulations, we then demonstrated that an intense - yet experimentally attainable - electric field of nanosecond duration can affect the bβ-tubulin's C-terminus conformations and also influence local electrostatic properties at the GTPase as well as the binding sites of major tubulin drugs site. Our results suggest that intense nanosecond electric pulses could be used for physical modulation of microtubule dynamics. Since a nanosecond pulsed electric field can penetrate the tissues and cellular membranes due to its broadband spectrum, our results are also potentially significant for the development of new therapeutic protocols.

• MeSH
• elektrická stimulace * metody   MeSH
• lidé MeSH
• simulace molekulární dynamiky * MeSH
• statická elektřina MeSH
• tubulin fyziologie   MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• tubulin MeSH

The mechanical properties of microtubules are of great importance for understanding their biological function and for applications in artificial devices. Although microtubule mechanics has been extensively studied both theoretically and experimentally, the relation to its molecular structure is understood only partially. Here, we report on the structural analysis of microtubule vibration modes calculated by an atomistic approach. Molecular dynamics was applied to refine the atomic structure of a microtubule and a C α elastic network model was analyzed for its normal modes. We mapped fluctuations and local deformations up to the level of individual aminoacid residues. The deformation is mode-shape dependent and principally different in α-tubulins and β-tubulins. Parts of the tubulin dimer sequence responding specifically to longitudinal and radial stress are identified. We show that substantial strain within a microtubule is located both in the regions of contact between adjacent dimers and in the body of tubulins. Our results provide supportive evidence for the generally accepted assumption that the mechanics of microtubules, including its anisotropy, is determined by the bonds between tubulins.

• MeSH
• aminokyseliny chemie   metabolismus   MeSH
• anizotropie MeSH
• konformace proteinů * MeSH
• mechanický stres MeSH
• mikrotubuly chemie   metabolismus   MeSH
• multimerizace proteinu MeSH
• sekvence aminokyselin MeSH
• simulace molekulární dynamiky * MeSH
• tubulin chemie   metabolismus   MeSH
• vibrace MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• tubulin 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.

• Klíčová slova
• LDH virus, cancer biophysics, disturbed coherence, microtubule oscillations, mitochondrial dysfunction, water ordering,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This paper describes a proposed biophysical mechanism of a novel diagnostic method for cancer detection developed recently by Vedruccio. The diagnostic method is based on frequency selective absorption of electromagnetic waves by malignant tumors. Cancer is connected with mitochondrial malfunction (the Warburg effect) suggesting disrupted physical mechanisms. In addition to decreased energy conversion and nonutilized energy efflux, mitochondrial malfunction is accompanied by other negative effects in the cell. Diminished proton space charge layer and the static electric field around the outer membrane result in a lowered ordering level of cellular water and increased damping of microtubule-based cellular elastoelectrical vibration states. These changes manifest themselves in a dip in the amplitude of the signal with the fundamental frequency of the nonlinear microwave oscillator-the core of the diagnostic device-when coupled to the investigated cancerous tissue via the near-field. The dip is not present in the case of healthy tissue.

• MeSH
• biofyzika přístrojové vybavení   metody   MeSH
• elektřina MeSH
• elektromagnetická pole * MeSH
• lidé MeSH
• mikrotubuly chemie   metabolismus   účinky záření   MeSH
• mikrovlny MeSH
• nádory diagnóza   metabolismus   patologie   MeSH
• pružnost MeSH
• studie případů a kontrol MeSH
• vibrace MeSH
• voda chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• voda MeSH