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