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To develop and reliably use diagnostic and therapeutic methods employing microwaves, we need to have an accurate knowledge of biological dielectric properties. Traditionally, dielectric properties of biosamples are determined experimentally. However, such measurements require dedicated hardware and physical availability of sufficient volume of biological samples of interest. Instead, here, we demonstrate the prediction of complex permittivity of a simple biomolecular sample using computational molecular dynamics simulations. We focus here on the role of a molecular model of water since it is the major compound determining microwave dielectric properties of biological tissues and wet samples. Here, for the first time, we analyze how the common molecular water models (SPC/E, TIP3P, and TIP4P) affect complex permittivity of biomolecular solutions predicted by molecular dynamics simulations. We found that the type of the molecular water model used in the simulation affects not only water contribution but also biomolecule contribution to the permittivity spectra. Our results contribute to in silico prediction and understanding of dielectric properties of biomaterials.

Remodeling of nanoscopic structures is not just crucial for cell biology, but it is also at the core of bioinspired materials. While the microtubule cytoskeleton in cells undergoes fast adaptation, adaptive materials still face this remodeling challenge. Moreover, the guided reorganization of the microtubule network and the correction of its abnormalities is still a major aim. This work reports new findings for externally triggered microtubule network remodeling by nanosecond electropulses (nsEPs). At first, a wide range of nsEP parameters, applied in a low conductivity buffer, is explored to find out the minimal nsEP dosage needed to disturb microtubules in various cell types. The time course of apoptosis and microtubule recovery in the culture medium is thereafter assessed. Application of nsEPs to cells in culture media result in modulation of microtubule binding properties to end-binding (EB1) protein, quantified by newly developed image processing techniques. The microtubules in nsEP-treated cells in the culture medium have longer EB1 comets but their density is lower than that of the control. The nsEP treatment represents a strategy for microtubule remodeling-based nano-biotechnological applications, such as engineering of self-healing materials, and as a manipulation tool for the evaluation of microtubule remodeling mechanisms during various biological processes in health and disease.

Knowledge of electromagnetic properties of biomolecules is essential for a fundamental understanding of electric field interaction with biosystems and for development of novel biomedical diagnostic and therapeutic methods. To enable systematic analysis of the dielectric properties of biomolecule solutions we presented here a method for a rational design of radiofrequency and microwave chip for quantitative dielectric sensing. At first, we estimated the primary frequency band of interest using a relaxation time of targeted molecule via the Stokes–Einstein–Debye equation. Then we proposed a microwave sensing chip for the estimated frequency band and evaluated its performance using both analytical modeling and numerical electromagnetic simulations. We fabricated the chip and experimentally demonstrated that we can extract the complex permittivity (0.5–40 GHz) of the water solution of alanine – one of the most common proteinogenic amino acids – without any calibration liquid and with about 20-fold smaller volume than with commercial methods. The observed dependence of extracted complex permittivity on the alanine concentration was interpreted using molecular dynamics simulations. The procedure we described here can be applied for the development of dielectric sensing method of any polar biomolecule solution.

There has been extensive study on the vibration dynamics and fluctuations of microtubules in the quest for understanding the relation between microtubule material properties and their ability to carry out several functions in cells. While experimental fluctuation analysis of microtubules has provided an important piece of knowledge about microtubule mechanics, models of microtubule vibrations struggle with providing experimentally testable and biologically relevant predictions. In this mini-review, we critically analyze models of microtubule vibration dynamics, mainly focusing on limitations of particular modeling approaches and their relevance to observed and hypothesized biological phenomena. We assess the possibility of coherent microtubule vibrations in vivo, which is the corner-stone of hypotheses about cellular electromagnetic activity, and we discuss experimental approaches which could resolve controversies about microtubule vibrations.

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.

Self-assembly is at the heart of many promising nanoscience technologies as well as at the core of life processes. Tubulin proteins self-assemble into microtubules, tube-like structures that are essential in cellular functions such as cell division and intracellular transport and also a major target in cancer therapies. Therefore, it is crucial to develop efficient methods for monitoring tubulin self-assembly at the molecular level. To mitigate the limitations of current methods, we propose a new approach based on a microwave lab-on-a-chip method to monitor tubulin self-assembly states. To that end, we designed a dedicated microwave platform with integrated microfluidics with a sensing volume of 30 nL. In parallel, we used a standard bulk light-scattering-based method to assess the tubulin self-assembly and to validate the microwave chip results. Using our chip, for the first time, we demonstrate that the self-assembly state of tubulin into microtubules can be monitored using microwave microfluidics technology. Our results introduce a novel label-free electromagnetic monitoring and analytical method for bionanotechnology and biomedicine applications that can potentially be integrated into advanced microscopy systems.

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 intra-cellular components such as cytoskeletal proteins could be directly influenced by electric pulses within biomedically-attainable parameters. 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 β-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 novel therapeutic protocols.Author summaryα/β-tubulin heterodimers are the basic building blocks of microtubules, that form diverse cellular structures responsible for essential cell functions such as cell division and intracellular transport. The ability of tubulin protein to adopt distinct conformations contributes to control the architecture of microtubule networks, microtubule-associated proteins, and motor proteins; moreover, it regulates microtubule growth, shrinkage, and the transitions between these states. Previous recent molecular dynamics simulations demonstrated that the interaction of the tubulin protein macrodipole with external electric field modifies orientation and conformations of key loops involved in lateral contacts: as a result, the stability of microtubules can be modulated by such fields. In this study, we seek to exploit these findings by investigating the possibility of fine-tuning the dipolar properties of binding sites of major drugs, by means of the action of electric fields. This may open the way to control tubulin-drug interactions using electric fields, thus modulating and altering the biological functions relative to the molecular vectors of microtubule assembly or disassembly. The major finding of our study reveals that intense (> 20 MV/m) ultra-short (30 ns) electric fields induce changes in the major residues of selected binding sites in a field strength-dependent manner.

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.

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.

An important dielectric signature of biosamples is related to rotational dynamics of water molecules with relaxation times at picosecond scale. In this paper, we first identify that when the water relaxation time increases, the most significant change in imaginary part of permittivity occurs at around 8 GHz and 40 GHz. To sensitively capture this permittivity change we designed a sensing electromagnetic structure based on periodically modulated coplanar waveguide with a sharp transmission resonance at around 40 GHz within the bandgap due to defect in periodicity. In simulation, we then demonstrated that the central frequency and width of resonance peak is sensitive to changes of water relaxation time which can occur due to biomolecule presence. Up to our knowledge, this is the first time a defected electromagnetic bandgap structure is proposed for microwave biosensing.

Knowledge of biological dielectric properties is fundamental for a development of biomedical microwave diagnostic and therapeutic methods. Dielectric properties of biosamples are traditionally obtained by measurement. However, such measurements might be cost prohibitive in case of expensive purified biosamples and large sample volumes required by commercial methods of dielectric spectroscopy. Here we demonstrate how to use molecular dynamics simulations to computationally predict a complex permittivity of biomolecule solution in the microwave band. We verify how complex permittivity data obtained from a simulation match the data obtained from experiment. We suggest that molecular dynamics simulations can not only rationalize a design of microwave biosensors but also aid to decipher measured microwave dielectric spectra a posteriori.

Functions of proteins and interactions between them are primarily based on electric and electrodynamic forces. Charge distribution and fluctuations of the individual atomic groups on proteins generates local electric field that ultimately determines how proteins bind and interact. Possibility of modifying and possibly controlling protein function by external electric field lends itself as a tool for both understanding and controlling biological processes. Here we demonstrate, using molecular dynamics, that intense, yet experimentally attainable, electric field affects tubulin dimer conformation within several nanoseconds. We focused on the effects of electric field on the structure and dynamics of C-terminus of beta tubulin. The tail of C-terminus (i) is important for interactions with other proteins such as motor proteins and microtubule severing proteins, (ii) is a major site for mutations and post-translational modifications, (iii) possesses a significant fraction of tubulin electric charge hence it is a natural target of electric field effects.

In this paper, a coplanar microwave sensor is proposed to detect the biomolecules in aqueous solution. The proposed coplanar sensor is imprinted on the ground plane of the microstrip line, while microstrip to coplanar waveguide transition is achieved using via. The proposed design is highly compatible for study of the broadband electromagnetic properties of biological sample in the laboratory. A custom-designed thru-reflect-line approach is used for calibration of the vector network analyzer. The proposed microwave sensor is designed, fabricated and tested with various concentrations (50, 100, and 150 mg/mL) of a -amino acid viz. L-cysteine, which is an important stabilizing and redox active residue common in many proteins, in the frequency range of 500 MHz - 6.5 GHz.

There is a need for accurate knowledge of complex permittivity of biosystems for development of electromagnetic diagnostic and therapeutic methods. However, standard open-ended coaxial probe method for measurement of complex permittivity requires rather large sample volumes which is prohibitive for analysis of many types precious biomolecules available only in small volumes. To help to alleviate this issue, we have designed, fabricated and tested a novel grounded coplanar waveguide-based sensor for dielectric spectroscopy of small volumes for the 0.5–50 GHz band. Our method (i) enables 20-fold lower sample volumes than the standard open-end coaxial probe method, (ii) does not require a reference liquid to obtain absolute values of complex permittivity, (iii) is microfluidics-free and the whole sensor can be fabricated by standard printed circuit board techniques. We believe that our sensor and method contributes to low-cost broad band acquisition of complex permittivity data of biomaterials and biomolecules which can be used for development of new therapeutic and diagnostic methods.

Tubulin self-assembly into microtubules is a fascinating natural phenomenon. Its importance is not just crucial for functional and structural biological processes, but it also serves as an inspiration for synthetic nanomaterial innovations. The modulation of the tubulin self-assembly process without introducing additional chemical inhibitors/promoters or stabilizers has remained an elusive process. This work reports a versatile and vigorous strategy for controlling tubulin self-assembly by nanosecond electropulses (nsEPs). The polymerization assessed by turbidimetry is dependent on nsEPs dosage. The kinetics of microtubules formation is tightly linked to the nsEPs effects on structural properties of tubulin, and tubulin-solvent interface, assessed by autofluorescence, and the zeta potential. Moreover, the overall size of tubulin assessed by dynamic light scattering is affected as well. Additionally, atomic force microscopy imaging reveals the formation of different assemblies reflecting applied nsEPs. It is suggested that changes in C-terminal modification states alter tubulin polymerization-competent conformations. Although the assembled tubulin preserve their integral structure, they might exhibit a broad range of new properties important for their functions. Thus, these transient conformation changes of tubulin and their collective properties can result in new applications.

© 2018 IOP Publishing Ltd. This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world.

Paper deals with a description of research activities in the field of Microwave Medical Diagnostics and Treatment done at the Dept. of EM Field, Czech Technical University (CTU) in Prague. History of these activities goes to year 1981, when the first apparatus for microwave hyperthermia cancer treatment has been developed at CTU and one year later started to be used for oncological patient treatments at Institute of Radiation Oncology (Hospital Bulovka in Prague).

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.

Accurate knowledge of electromagnetic properties of biosystems is essential for the novel physical methods for therapy and diagnostics in medicine and biotechnology.To study the dynamics and electrical properties of biomolecules, we have designed, fabricated, and tested novel grounded coplanar waveguide-based chip for dielectric spectroscopy of liquid samples in 0.5 - 40 GHz band made on RO4350B substrate and we implemented a method for the permittivity extraction based purely on the extraction from measured scattering parameters.To our knowledge, the proposed bio sensing method represents an advantage over the current known sensing chips because the dielectric function of sample is obtained purely by using precision calibration techniques (NIST multi-line TRL) and computational optimization (CST Microwave Studio) without any a priori assumption about the dielectric model of measured sample. This chip is designed with well-defined active area to achieve the high sensitivity to dielectric change, enables perfect repeatability of sample position without the need of any microfluidics. Furthermore, due to its sensing size, the chip permits to work with only 250 microliter sample volume.In the pioneering experiments, we focused on dielectric (i.e. polarization) properties of solutions of amino acids, as building blocks of proteins. Alanine has been selected. The polar nature of amino acids determines their behavior in aqueous solutions and due to fact that at least one relaxation process is anticipated in microwave band, it allows us to study their dynamics and structure which employ using broadband dielectric spectroscopy. Data extracted from experiment are in an exact agreement in comparison with widely used commercial reflection method by coaxial probe (85070E Dielectric Probe Kit). Data show the trend of rising static permittivity at low frequencies with rising concentration of amino acids and also show the shift of relaxation times. We also performed molecular dynamics simulations to predict the complex permittivity of amino acid solution and obtained good agreement with experimental data. The presented procedure enables simple experimental verification of molecular dynamics of biomolecules by the dielectric spectroscopy using our microvolume chip.We acknowledge support by the Czech Science Foundation, project no. P102/15-17102S. Authors participate in COST Action BM1309 and bilateral exchange project between Czech and Slovak Academies of Sciences, no. SAV-15-22.

In this chapter we shall focus on the needs that many researchers, scientists and even students have very often. When using commercial simulation software for numerical simulation of electromagnetic field we frequently encounter many insufficiencies which those software products have. Usually, main aim of computational software developers is to optimize and refine so called core of these programmes – EM field solver. After that CAD (Computer Assisted Design) and post processing parts of EM simulators are dealt with. Mainly this can be an issue with newer, short-time in development products but one’s own post processing using Matlab can be greatly beneficial even when using well established simulators of EM field. This is largely due to its flexibility which cannot be overcome by any EM field simulator.

Field of microwave applications is expanding very rapidly and it already encompasses very wide spectrum of common and well developed medical and industrial procedures. It is very important for further research that there are reliable means of analyzing effects of electromagnetic field on various materials in real-time. In this paper we present our design approach of microwave applicator for visualization purposes. We also present results and their interpretation.

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.

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. It recently was determined from anisotropic elastic network modeling of entire microtubules that the frequencies of microtubule longitudinal axial eigenmodes lie in the region of tens of GHz for the physiologically common microtubule lengths. We calculated electric field generated by axial longitudinal vibration modes of microtubule, which model is based on subnanometer precision of charge distribution. Due to elastoelectric nature of the vibrations, the vibration wavelength is million-fold shorter than that of the electromagnetic field in free space and the electric field around the microtubule manifests rich spatial structure with multiple minima. The dielectrophoretic force exerted by electric field on the surrounding molecules will influence the kinetics of reactions 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 a role in biological self-organization.

Microtubules are important organizing structures of eukaroytic cells. They are electrically polar and have collective vibration modes from kHz to low THz region. In approximation of microtubule subunits (tubulin molecules) as rigid particles, we calculate electric field generated by optical branch of axial longitudinal vibration modes of microtubule. This oscillatory electric field, due to its complex spatial distribution, may play an important role in cellular temporal and spatial organization.

Certain structures in a living cell may generate electric oscillations. Microtubules, which form a part of a cellular skeleton, belong to this class of structures and fulfill all conditions for generation of electric oscillations in kHz÷GHz band. We present selected results from calculations of the oscillatory electric field generated by higher vibration modes of microtubules. We propose that the electric field of certain modes may play specific function in cellular organization.

Microtubules are important structures in the cytoskeleton which organizes the cell. A single microtubule is composed of electrically polar structures, tubulin heterodimers, which have a strong electric dipole moment. Vibrations are expected to be generated in microtubules, thus tubulin heterodimers oscillate as electric dipoles. This gives rise to an electromagnetic field which is detected around the cells. We calculate here the electromagnetic field of microtubules if they are excited at 1 GHz. This paper includes work done for the bachelor thesis of the first author.

Thanks to their material properties, microtubules can play complex variety of biological functions. Experimental studies have shown that mechanical characteristics of microtubules are length-dependent and anisotropic, however, the origin of this feature has not been traced down to the level of tubulin sequence yet. Here we use high-resolution elastic network model to show local deformations patterns in microtubule structure up to the level of individual amino acid residues. The mechanical strain within the molecular structure of a microtubule is, according to our results, localized to interdimer contacts with energetic preference of deformation in longitudinal contacts. These findings are in agreement with reported mechanical anisotropy of microtubules, i.e. higher Young's modulus in axial direction compared to radial direction. Our results contribute to understanding the origin of deformability of microtubules on the molecular level, which is important for prospective targeting of microtubules in medical therapeutic strategies.

Electromagnetic activity of cells (>100 kHz) beyond the conventional frequency region of electrophysiology is poorly explored, yet it offers opportunities for new diagnostic and therapeutic methods in bioelectronic medicine and may provide insights into new general mechanism in cellular signalling. Here, we describe electromagnetic properties of microtubules, protein nanostructures omnipresent in biological systems, and how they are predicted to be involved in cellular electromagnetic activity (10 MHz - 10 GHz). Authors were supported from institutional funding of the Institute of Photonics and Electronics, The Czech Academy of Sciences and by the Czech Science Foundation, grant no. 15-17102S.

Microtubules are known to be involved in intracellular signaling. Here, we show in silico that electrically polar collective vibration modes of microtubules form electric oscillating potential which is quasi-periodic both in space and in time. While single mode microtubule vibration excites an electric field with spatially stationary local minima and maxima of the electric field, the multimode excitation causes the formation of an electric pulse and many transient local electric field minima. The biophysical mechanism we describe lends support to the view that microtubules may comprise a substrate for ultra-fast electrical signaling in neurons or other living cells.

The cytoskeleton, especially microtubules, is potential source of electrodynamic field of living eukaryote cells. Microtubule network is a very dynamic structure which is composed of highly polar molecules - tubulin heterodimers. Microtubules have their eigenmode vibrations in frequency range from kHz to GHz. We approximated electrical properties of tubulin heterodimer as an elementary electric dipole and described the longitudinal mechanical oscillation of one microtubule by spatial modulation function. Mechanical oscillations of tubulin heterodimers were approximated as a chain of rigid particles and described by the spatial modulation function. An optical branch was used as it is more efficient for generation of electromagnetic field. We also created asymmetrical model of microtubule network of dividing cell and symmetrical model of microtubule network of non-dividing cell. The field around oscillating microtubule was calculated as a vector sum of contributions from all elementary electric dipoles. Finally, we performed calculations with several cell sizes and numbers of microtubules in models and performed comparative analysis.

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, strong static electric field, and water ordering around them in cytosol - that are necessary conditions for generation of coherent electrodynamic field by microtubules. Electrodynamic forces are of a long-range nature in comparison with bond and cohesive forces. Mitochondrial dysfunction leads to disturbances of the electromagnetic field; its power and coherence may be diminished, and frequency spectrum altered. Consequently, defective electrodynamic interaction forces between cancer and healthy cells may result in local invasion of cancer cells. Further deformation of interaction forces connected with experimentally disclosed spatial disarrangement of the cytoskeleton and disordered electrodynamic field condition metastatic process. Cancer therapeutic strategy targeting mitochondria may restore normal physiological functions of mitochondria and open the apoptotic pathway. Apoptosis of too much damaged cancer cells was observed. Considerable experience with DCA (dichloroacetate) cancer treatment in humans was accumulated. Clinical trials should assess DCA therapeutic potential and collect data for development of novel more effective drugs for mitochondrial restoration of various cancers.

Cytoskeleton is a crucial integrating component of cellular functions. Microtubules, as a part of cytoskeleton, are involved in such functions, serving as transportation tracks, signaling substrate and also are fundamental for cellular division. While chemical, mechanical and electrostatic nature of microtubule function in these cellular processes is being researched, current picture of all underlying types of interactions is far from complete.Here, we introduce a new, electrodynamic aspect of microtubule interaction with its molecular partners from combination of the knowledge of atomic-precision electric charge distribution with fast mechanical fluctuation properties of microtubules.First, a microtubule lattice is reconstructed from combined RCSB Protein DataBank 1TUB and 1JFF tubulin structure and interlocking alpha-tubulin loops between adjacent protofilaments are remodeled to obtain physiological conformation. We analyze normal modes of anisotropic elastic network microtubule model obtained by coarse-graining the atomic model and using rotating block approximation. Further, we map the atomic charge distribution upon atomic trajectories of the first 30 normal modes, which lie in GHz spectral region. Approximating the oscillating atomic charges as a Hertzian dipoles, we calculated and visualized electrodynamic field around the microtubule for each normal mode.Based on the results, we suggest that the electrodynamic field around microtubule can provide interactions of different nature than pure electrostatic interactions since the ionic screening is diminished for frequency the electric >10 MHz.Significance of these unique theoretical predictions is planned to be verified in the upcoming experimental studies. Exploitation of microtubule electrodynamic properties could open paths to novel tools for microtubule manipulation with prospects in new therapeutic and diagnostic methods in the future.