Evidences of plasma membrane-mediated ROS generation upon ELF exposure in neuroblastoma cells supported by a computational multiscale approach

Background

Molecular mechanisms of interaction between cells and extremely low frequency magnetic fields (ELF-MFs) still represent a matter of scientific debate. In this paper, to identify the possible primary source of oxidative stress induced by ELF-MF in SH-SY5Y human neuroblastoma cells, we estimated the induced electric field and current density at the cell level.

Methods

We followed a computational multiscale approach, estimating the local electric field and current density from the whole sample down to the single cell level. The procedure takes into account morphological modeling of SH-SY5Y cells, arranged in different topologies. Experimental validation has been carried out: neuroblastoma cells have been treated with Diphenyleneiodonium (DPI) -an inhibitor of the plasma membrane enzyme NADPH oxidase (Nox)- administered 24 h before exposure to 50 Hz (1 mT) MF.

Results

Macroscopic and microscopic dosimetric evaluations suggest that increased current densities are induced at the plasma membrane/extra-cellular medium interface; identifying the plasma membrane as the main site of the ELF-neuroblastoma cell interaction. The in vitro results provide an experimental proof that plasma membrane Nox exerts a key role in the redox imbalance elicited by ELF, as DPI treatment reverts the generation of reactive oxygen species induced by ELF exposure.

https://www.sciencedirect.com/science/article/pii/S0005273619301373?via%3Dihub

On the magnetosensitivity of lipid peroxidation: two- versus three-radical dynamics

We present a theoretical analysis of the putative magneto sensitivity of lipid peroxidation. We focus on the widely accepted radical pair mechanism (RPM) and a recently suggested idea based on spin dynamics induced in three-radical systems by the mutual electron–electron dipolar coupling (D3M).

Most chemical reactions are insensitive to the weak magnetic fields that pervade our everyday surroundings.  An exception to this rule is the recombination of radical pairs, which depends on the overall electron spin of the reactants.  As a consequence of weak magnetic interactions modulating the overall spin of the radicals, the associated recombination yields are, at least in principle, susceptible to the strength and direction of external magnetic fields.

https://www.researchgate.net/publication/333848825_On_the_magnetosensitivity_of_lipid_peroxidation_two-_versus_three-radical_dynamics

The future of quantum biology

 How does DNA, with stacked nucleotides separated by about 0.3 nm, deal with UV photons?

How does an enzyme catalyze an essential biochemical reaction?

How does our brain with neurons organized on a sub-nanometer scale deal with such an amazing amount of information?

How do DNA replication and expression work?

All these bio-logical functions should, of course, be considered in the context of evolutionary fitness.

The differences between a classical approximation and a quantum-mechanical model are generally thought to be negligible in these cases, even though at the basis every process is entirely governed by the laws of quantum mechanics.

https://www.researchgate.net/publication/328934332_The_future_of_quantum_biology

Experimental Demonstration That Aharanov-Bohm Phase Shift Voltages In Optical Coupler Circuits of Tuned Patterned Magnetic Fields Is Critical for Inhibition of Malignant Cell Growth

The physical processes by which specific point duration magnetic fields affect aberrant expressions of living matter may involve  non-classical  mechanisms.    The  Aharanov-Bohm  voltage  for  a  quantum  of  energy  that  is  convergent  with  the quotient of the proton’s magnetic moment to its charge multiplied by the viscosity of water at homeostatic  temperatures applied  across  the  distance  of  O-H  bonds  in  conjunction  with  its  phase  modulation  is  about  ±4.3  V.  Application  of frequency  shifting,  temporally-patterned  magnetic  fields  produced  by  3  ms  point  durations  at  average  intensities  of  ~28mG (that are equivalent to Nernst thresholds for plasma membranes) generated through optocoupler light emitting diodes produced  the  strongest  inhibition  of  malignant  cells  growth  when  the  pre-coupler  value  for  the  circuit  maintenance  was ±4.3 V compared to increments of voltage below or above this value. Spatial expansion of the effective zone for growth diminishment  also  occurred  with  this  pre-voltage  level.  These  results  indicate  that  phase  modulation  of  the  electrons mediating cellular molecular pathways may be central to the etiology and potential treatment of malignant cells but not for normal  cells’dynamics.  Consideration  of  quantum  effects  rather  than  classical  electromagnetic  theory  may  be  a  more effective strategy for impeding the physical bases for the molecular pathways that define malignant cells.

https://www.researchgate.net/publication/328720507_Experimental_Demonstration_That_Aharanov-Bohm_Phase_Shift_Voltages_In_Optical_Coupler_Circuits_of_Tuned_Patterned_Magnetic_Fields_Is_Critical_for_Inhibition_of_Malignant_Cell_Growth

Tumour-treating fields (TTFields): Investigations on the mechanism of action by electromagnetic exposure of cells in telophase/cytokinesis

Tumour-treating fields (TTFields) use alternating electric fields which interfere with dividing cells, thereby reducing tumour growth. Previous reports suggest that electrical forces on cell structure proteins interfered with the chromosome separation during mitosis and induced apoptosis. In the present report we evaluate electromagnetic exposure of cells in telophase/cytokinesis in order to further analyse the mechanism of action on cells. We performed numerical electromagnetic simulations to analyse the field distribution in a cell during different mitotic phases. Based thereon, we developed an electric lumped element model of the mitotic cell. Both the electromagnetic simulation and the lumped element model predict a local increase of the specific absorption rate (SAR) as a measure of the electromagnetically induced power absorption density at the mitotic furrow which may help to explain the anti-proliferative effect. In accordance with other reports, cell culture experiments confirmed that TTFields reduce the proliferation of different glioma cell lines in a field strength- and frequency-dependent manner. Furthermore, we found an additional dependence on the commutation time of the electrical fields. The report gives new insights into TTFields’ anti-proliferative effect on tumours, which could help to improve future TTFields application systems.
https://www.researchgate.net/publication/333088748_Tumour-treating_fields_TTFields_Investigations_on_the_mechanism_of_action_by_electromagnetic_exposure_of_cells_in_telophasecytokinesis

Life on Magnets: Stem Cell Networking on Micro-Magnet Arrays

Interactions between a micro-magnet array and living cells may guide the establishment of cell networks due to the cellular response to a magnetic field. 

To manipulate mesenchymal stem cells free of magnetic nanoparticles by a high magnetic field gradient, we used high quality micro-patterned NdFeB films around which the stray field's value and direction drastically change across the cell body. 

Such micro-magnet arrays coated with parylene produce high magnetic field gradients that affect the cells in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the directions parallel to the edges of the micro-magnet. 

To explain these effects, three putative mechanisms that incorporate both physical and biological factors influencing the cells are suggested. 

It is shown that the static high magnetic field gradient generated by the micro-magnet arrays are capable of assisting cell migration to those areas with the strongest magnetic field gradient, thereby allowing the build up of tunable interconnected stem cell networks, which is an elegant route for tissue engineering and regenerative medicine.

https://www.researchgate.net/publication/255737633_Life_on_Magnets_Stem_Cell_Networking_on_Micro-Magnet_Arrays

The subtle effects of low-frequency magnetic fields on oxidative metabolism, ROS signaling, and cellular growth

The effects of weak magnetic fields on the biological production of reactive oxygen species (ROS) from intracellular superoxide (O2•-) and extracellular hydrogen peroxide (H2O2) were investigated in vitro with rat pulmonary arterial smooth muscle cells (rPASMC). 

A decrease in O2•- and an increase in H2O2 concentrations were observed in the presence of a 7 MHz radio frequency (RF) at 10 μTRMS and static 45 μT magnetic fields. 

We propose that O2•- and H2O2 production in some metabolic processes occur through singlet-triplet modulation of semiquinone flavin (FADH•) enzymes and O2•- spin-correlated radical pairs. 

Spin-radical pair products are modulated by the 7 MHz RF magnetic fields that presumably decouple flavin hyperfine interactions during spin coherence. 

RF flavin hyperfine decoupling results in an increase of H2O2 singlet state products, which creates cellular oxidative stress and acts as a secondary messenger that affects cellular proliferation. 

This study demonstrates the interplay between O2•- and H2O2 production when influenced by RF magnetic fields and underscores the subtle effects of low-frequency magnetic fields on oxidative metabolism, ROS signaling, and cellular growth.

https://www.researchgate.net/publication/261220958_Spin_Biochemistry_Modulates_Reactive_Oxygen_Species_ROS_Production_by_Radio_Frequency_Magnetic_Fields

The effect of pulsed electromagnetic field exposure on osteoinduction of human mesenchymal stem cells cultured on nano-TiO2 surfaces.

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are considered a great promise in the repair and regeneration of bone. Considerable efforts have been oriented towards uncovering the best strategy to promote stem cells osteogenic differentiation. In previous studies, hBM-MSCs exposed to physical stimuli such as pulsed electromagnetic fields (PEMFs) or directly seeded on nanostructured titanium surfaces (TiO2) were shown to improve their differentiation to osteoblasts in osteogenic condition. In the present study, the effect of a daily PEMF-exposure on osteogenic differentiation of hBM-MSCs seeded onto nanostructured TiO2 (with clusters under 100 nm of dimension) was investigated. TiO2-seeded cells were exposed to PEMF (magnetic field intensity: 2 mT; intensity of induced electric field: 5 mV; frequency: 75 Hz) and examined in terms of cell physiology modifications and osteogenic differentiation. Results showed that PEMF exposure affected TiO2-seeded cells osteogenesis by interfering with selective calcium-related osteogenic pathways, and greatly enhanced hBM-MSCs osteogenic features such as the expression of early/late osteogenic genes and protein production (e.g., ALP, COL-I, osteocalcin and osteopontin) and ALP activity. Finally, PEMF-treated cells resulted to secrete into conditioned media higher amounts of BMP-2, DCN and COL-I than untreated cell cultures. These findings confirm once more the osteoinductive potential of PEMF, suggesting that its combination with TiO2 nanostructured surface might be a great option in bone tissue engineering applications.
https://www.ncbi.nlm.nih.gov/pubmed/29902240

Determinants of bioelectrical phase angle in disease

Phase angle (PhA), a parameter of bioelectrical impedance analysis, is a well-known predictor of morbidity and mortality in various diseases. The causes of decreased PhA are, however, not yet completely understood. We therefore investigated determinants of PhA in 777 hospitalised patients in a retrospective analysis. PhA was assessed by bioelectrical impedance analysis at 50 KHz. Subjective global assessment (SGA) was used to evaluate nutritional status. Age, sex, BMI as well as nutritional status (SGA), benign or malignant disease and C-reactive protein (CRP) were investigated as potential determinants of PhA and standardised PhA (SPhA) = (observed PhA - mean PhA of reference values)/standard deviation of reference values in a general linear model regression analysis. Next to age (estimated effect size, 46·6%; P<0·0001), malnutrition (39·1%; P<0·0001) emerged as a major PhA determinant in our study population. Moreover, sex (6·4%; P<0·0001), CRP (4·4%; P<0·0001) and BMI (3·5%; P < 0·0001) exhibited a significant influence on PhA, whereas malignant disease showed no significant effect in this model. The only significant determinants of SPhA were malnutrition (85·4%; P<0·0001) and inflammation (9·6 %; P<0·0001). In conclusion, next to the established predictors, malnutrition and inflammation have a strong impact on PhA in sick individuals, which partly explains its prognostic power. When investigating the SPhA, only malnutrition and inflammation were found to be significant predictors, as a result of which the SPhA is considered a more suitable indicator of nutritional and health status.
https://www.researchgate.net/publication/221810319_Determinants_of_bioelectrical_phase_angle_in_disease

Electroencephalographic field influence on calcium momentum waves

Macroscopic electroencephalographic (EEG) fields can be an explicit top-down neocortical mechanism that directly drives bottom-up processes that describe memory, attention, and other neuronal processes. The top-down mechanism considered are macrocolumnar EEG firings in neocortex, as described by a statistical mechanics of neocortical interactions (SMNI), developed as a magnetic vector potential A. The bottom-up process considered are Ca(2+) waves prominent in synaptic and extracellular processes that are considered to greatly influence neuronal firings. Here, the complimentary effects are considered, i.e., the influence of A on Ca(2+) momentum, p. The canonical momentum of a charged particle in an electromagnetic field, Π=p+qA (SI units), is calculated, where the charge of Ca(2+) is q=-2e, e is the magnitude of the charge of an electron. Calculations demonstrate that macroscopic EEG A can be quite influential on the momentum p of Ca(2+) ions, in both classical and quantum mechanics. Molecular scales of Ca(2+) wave dynamics are coupled with A fields developed at macroscopic regional scales measured by coherent neuronal firing activity measured by scalp EEG. The project has three main aspects: fitting A models to EEG data as reported here, building tripartite models to develop A models, and studying long coherence times of Ca(2+) waves in the presence of A due to coherent neuronal firings measured by scalp EEG. The SMNI model supports a mechanism wherein the p+qA interaction at tripartite synapses, via a dynamic centering mechanism (DCM) to control background synaptic activity, acts to maintain short-term memory (STM) during states of selective attention.
https://www.researchgate.net/publication/258635626_Electroencephalographic_field_influence_on_calcium_momentum_waves

Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects

The direct targets of extremely low and microwave frequency range electromagnetic fields (EMFs) in producing non-thermal effects have not been clearly established. However, studies in the literature, reviewed here, provide substantial support for such direct targets. Twenty-three studies have shown that voltage-gated calcium channels (VGCCs) produce these and other EMF effects, such that the L-type or other VGCC blockers block or greatly lower diverse EMF effects. Furthermore, the voltage-gated properties of these channels may provide biophysically plausible mechanisms for EMF biological effects. Downstream responses of such EMF exposures may be mediated through Ca(2+) /calmodulin stimulation of nitric oxide synthesis. Potentially, physiological/therapeutic responses may be largely as a result of nitric oxide-cGMP-protein kinase G pathway stimulation. A well-studied example of such an apparent therapeutic response, EMF stimulation of bone growth, appears to work along this pathway. However, pathophysiological responses to EMFs may be as a result of nitric oxide-peroxynitrite-oxidative stress pathway of action. A single such well-documented example, EMF induction of DNA single-strand breaks in cells, as measured by alkaline comet assays, is reviewed here. Such single-strand breaks are known to be produced through the action of this pathway. Data on the mechanism of EMF induction of such breaks are limited; what data are available support this proposed mechanism. Other Ca(2+) -mediated regulatory changes, independent of nitric oxide, may also have roles. This article reviews, then, a substantially supported set of targets, VGCCs, whose stimulation produces non-thermal EMF responses by humans/higher animals with downstream effects involving Ca(2+) /calmodulin-dependent nitric oxide increases, which may explain therapeutic and pathophysiological effects.

https://www.researchgate.net/publication/242331926_Electromagnetic_fields_act_via_activation_of_voltage-gated_calcium_channels_to_produce_beneficial_or_adverse_effects

Authors note: Order comes from chaos, the scientific community is adverse to this fact...

The Golden Principle, Quantum Critical State, and the Heisenberg's Uncertainty Principle

On the atomic scale particles do not behave as we know it in the macro-atomic world. New properties emerge which are the result of an effect known as the Heisenberg's Uncertainty Principle. In order to study these nanoscale quantum effects the researchers have focused on the magnetic material cobalt niobate. It consists of linked magnetic atoms, which form chains just like a very thin bar magnet, but only one atom wide and are a useful model for describing ferromagnetism on the nanoscale in solid state matter.

When applying a magnetic field at right angles to an aligned spin the magnetic chain will transform into a new state called quantum critical, which can be thought of as a quantum version of a fractal pattern. Prof. Alan Tennant, the leader of the Berlin group, explains "The system reaches a quantum uncertain -- or a Schrödinger cat state. This is what we did in our experiments with cobalt niobate. We have tuned the system exactly in order to turn it quantum critical."

By tuning the system and artificially introducing more quantum uncertainty the researchers observed that the chain of atoms acts like a nanoscale guitar string.

https://www.sciencedaily.com/releases/2010/01/100107143909.htm

Neutron spectroscopy measures the atomic and magnetic motions of atoms. 

https://www.isis.stfc.ac.uk/Pages/Neutron-spectroscopy.aspx

Electromagnetic Therapy: A Primer

Electromagnetic (EM) signals are increasingly used in both systemic and local medical applications. We attempt here to provide  an  outline  of  the  types  of  signals  currently  in  use.

This also necessitates a general introductory classification of EM signal types, based on how each signal varies in time.

Although EM medicine includes both diagnostic and ther-apeutic applications (Figure 34.1), the medical community is far more familiar with the former, especially with magnetic resonance  imaging  (MRI),  electromyography  (EMG),  electroencephalography (EEG), electrocardiography (EKG), and magnetocardiography (MKG).

There  are  historical  reasons  for  the  medical  unfamiliarity (even antipathy) with electromagnetically based therapies.

One has only to look at the beginnings of modern medicine in  the  United  States,  specifically  the  1910  Flexner  report1,2 that  provided  the  basis  for  medical  education  today.

Prior  to  this  report  there  was  widespread  use  of  electromagnetic  techniques  in  medicine,  often  little  more  than  late  nineteenth century versions of snake oil cures.

In great measure, the  present  aversion  to  electromagnetic  therapies  built  into  modern  medicine  is  a  direct  result  of  Victorian  age  quackery.

This  century-old  prejudice  has  carried  though  to  today  even  as  it  becomes  clearer  that  weak  (low  intensity)  magnetic fields exhibit physiological effects that must be considered  separately  from  those  caused  by  high  intensity  fields.

Although the effects related to exposures at large fields are, as a rule, readily explained by known physical interactions, usually  Faraday  induction  or  joule  heating,  the  weak-field  effects, often rather robust, remain mostly unexplained.

This has unfortunately opened the door for many electromagnetic nostrums of dubious value.A  few  of  the  examples  we  mention  below  illustrate  the  useful therapeutic delivery of heat by electromagnetic means.

The most interesting applications are, however, nonthermal.

Further,  we  exclude  from  our  discussion  treatments  that  involve signals directly applied to specific regions of the body by  subcutaneous  means,  such  as  pacemakers,  defibrillators,  deep  brain  stimulators  (DBS),  etc.

Unlike  electromagnetic  applications, which are mostly unexplained, these represent techniques for replacing or enhancing faulty existing physi-ological electrical stimulations.
(PDF) Electromagnetic Therapy: A Primer.
https://www.researchgate.net/publication/303911386_Electromagnetic_Therapy_A_Primer

Statistical analysis and prospective application of the GM-scale, a semi-harmonic EMF scale proposed to discriminate between 'coherent' and 'decoherent' EM frequencies on life conditions

Remember Nobel prize awarded recently for circadian rhythm in biology:

"The Generalized Music (GM)-scale is an acoustic (octave-like) algorithm of 12 tones that describes the electromagnetic (EM) frequency band pattern discovered from a meta-analysis of in total 468 biomedical research papers. 

These studies reported either beneficial or detrimental effects of electromagnetic frequencies (EMF) on biological tissues/cells in vitro or whole organisms in vivo. 

The apparent quantized pattern of EM frequency bands was postulated to represent a potential 'quantum algorithm of life'. 

In the present paper a statistical analysis is made of the overall data underlying this patterned EM frequency distribution. 

Data were sorted according to their features to be either beneficial, 'coherent' frequencies or detrimental, 'decoherent' frequencies and grouped around the theoretical 12 GM-scale values. 

A Wilcoxon rank sum test was used to discriminate between these data populations and this test showed that the difference between the 'coherent' and 'decoherent' data sets is indeed statistically significant (p<0.0025) for all of the 12 GM-scale groups. 

The mean values of the groups correspond very well with the postulated GM-scale values (difference <0,9%). 

To analyze the fit of the biomedical EM-frequency data to the GM-scale algorithm values, 24 alternating and "decoherent' frequency bands were defined and the life data were plotted in these bands. 

This test showed that 89.4% of 'coherent' data and 83.4% of 'decoherent' data corresponded to their respective frequency bands. 

The particular band widths, and consequently the related error margins, are very small (2.6%-3.3%). 

A prospective method is demonstrated to apply the GM-scale algorithm to identify (label) experimental or already published EM frequency data as potential "coherent' or "decoherent'. 

These and future analyses of experimental data with respect to the fit of their EM frequencies to the GM-scale will help to further validate this algorithm as a new biophysical principle."

https://www.researchgate.net/publication/333844547_Statistical_analysis_and_prospective_application_of_the_GM-scale_a_semi-harmonic_EMF_scale_proposed_to_discriminate_between_'coherent'_and_'decoherent'_EM_frequencies_on_life_conditions