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The Cancer Cell Plasma Membrane Potentials as Energetic Equivalents to Astrophysical Properties
Abstract
The primary physical and chemical parameters that define the hypopolarized plasma cell membrane of malignant (cancer) cells compared to non-malignant cells reflect universal characteristics. The median value for the resting membrane potential is the constant for the Nernst equation without reference to discrepancies in ion concentrations and is identical to Boltzmann energies at 37 °C. The threshold energy defining space-time converges with access to entropic processes that are reflected in the morphology of cancer cells and tumors. Slowing of growth in cancer cell lines but not normal cells following exposure to weak (~1 to 10 μT) patterned magnetic fields occurs when the energy induced within the cell corresponds to the energy equivalent of the hypopolarized membrane potential. The optimal temporal parameters for the efficacy of these fields can be derived from Hubble’s parameter and the transform function for “noise” or “random” patterns within the system. Quantitative solutions and experimental data indicate that the cancer cell may be dominated by entropic process that can be attenuated or blocked by temporally-structured applied magnetic fields whose intensity matches the increment of energy associated with this threshold.
... The effective zone, within which the largest cell effects have been demonstrated, was described previously [11]. This threshold for an effect was predicted quantitatively by Persinger and Lafrenie [12] and was based upon the magnetic field energy equivalent of the Nernst solution (~26 mV) for plasma membranes independent of disparity of cation or anion concentrations. This was considered critical because most malignant cells display plasma membrane resting membrane potentials within this range rather than the "normal" cell values of between -55 mV to -90 mV [13]. ...
... The exclusion zone (EZ) is associated with a 10 fold increase in viscosity and the creation of a layer of protons whose potential difference is up to 150 mV or the value that has been classically attributed to disparity of ion (e.g., potassium or chloride) concentrations across the plasma cell membrane. As described by Persinger and Lafrenie [12], almost all malignant cell membranes exhibit values similar to base Nernst solutions (26 mV). The magnetic field required to equate this voltage is about 28 mG, which is the average value with which we obtained our effects. ...
... The precision of the 3 ms point duration may reflect a specific feature of proton dynamics within local and nonlocal space [25] that was predicted by Persinger and Lafrenie [12] and may involve contributions from cosmological sources that emphasize the interaction between the photon and proton-electron dynamics [3,26]. Given the intricate relationship between the viscosity of water and magnetic fields [7], the appearance of this state [27] in interfacial water, and the potential role of biological water dynamics (and entropy) in cancer [28], a more profound biophysical origin might be responsible for this manifestation of matter. ...
         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 ~28 mG (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.
... Whether the microbubbles and their "claimed effect" are a consequence of thermal or other non-thermal effects is not established. They could as well be a product of electrolytic process, since human cells interact with a variety of ions of imbalanced concentrations on opposite sides of the membrane (K + , Na + , Ca 2+ ) (Lobikin et al. 2012;Persinger and Lafrenie 2014). The thermal effect, according to Choi et al. (2011), is supposed to be dependent on its severity, influenced by thermal intensity and duration at high temperatures. ...
... The potential effect of the external electric field on cancer cells has also been linked to the electrical properties of the cells, through the bioelectric interaction of the cytoplasm with the extracellular environment. It has been reported that by manipulating the electric potential gradient between the cytoplasm and the extracellular environment (V m ), making it more negative (hyperpolarizing), the division of cancer cells is blocked in the V m range of − 45 to − 75 mV (Schwab et al. 2012;Persinger and Lafrenie 2014). The cancer cell cycle resumes on depolarizing the membrane to around − 10 mV. ...
... The cancer cell cycle resumes on depolarizing the membrane to around − 10 mV. The manipulation of V m by an alternating electric field has been associated with the field effect on the distribution of the essential ions in the cytoplasm and the cell membrane (Lobikin et al. 2012;Persinger and Lafrenie 2014). Because V m is critical for the permeability of different ions and the cell functions, its modulation would certainly influence the cell behavior. ...
Background
A number of experimental research findings for the metal nanoparticles (NPs)-mediated EMF photothermal therapy of cancer cells show an intriguing trend of the NPs’ size-dependent efficacy. This is a phenomenon we find to trend with the light absorption bandwidth behavior (full width at half maximum) of the NPs and the accompanying electric field enhancement. We find that the nanoparticle sizes that have been reported to produce the optimized effect on cancer cells are of minimum absorption bandwidth and optimized electric field magnitude. While the death of cancer cells under the NPs-aided EMF effect has in the past attracted varied interpretations, either as a thermal or non-thermal effect, photothermal effect has gained a wide acceptance due to the exhibited hyperthermia. However, the exhibited trend of the NPs’ size-dependent efficacy is beginning to feature as a possible manifestation of other overlooked underlying or synergistic phenomenal conditions.
Method
We present a theoretical model and analysis which reveal that the contribution and efficacy of the metal NPs in the destruction of cancer depend partly but significantly on the accompanying electric field intensity enhancement factor and partly on their absorption cross-section.
Results
This paper finds that, other than the expected hyperthermia, the metal NPs’ sizes for the optimized therapy on cancer cells seem to fulfill other synergistic conditions which need to come to the fore. We find interplay between electric field and thermal effects as independent energy channels where balancing may be important for the optimized EMF effect, in the ratio of about 5:1. The required balancing depends on the absorption bandwidth and absorption cross-section of the NPs, the frequency of EMF used and the relative permittivity of the cancer cells. The NPs’ size-dependent efficacy decreases away from the NPs’ size of minimum absorption bandwidth, which is around 20 nm for Au NPs or other shapes of equivalent surface area–volume ratio. While the absorption wavelength peak for metal NPs would change with the change of shape, the responsible condition(s) for optimizing the efficacy remains relatively invariable.
Conclusion
From the modeling and the analysis of the NPs’ size for optimizing the EMF therapy on cancer cells, the ratio of electric field enhancement by metal NPs to the associated thermal effect is a very important factor for efficacy.
... Decades of research have shown that the membrane potential in cancer cells is different from the membrane potential in normal cells [17]. Experimental data shows tumor cells have a membrane potential of approximately −26.7 mV, in contrast to normal cells, which have a membrane potential of approximately −70 mV to −90 mV [18]. Furthermore, when tumor cells begins to divide, the membrane potential falls to approximately −15 mV, and returns back to normal after completing division [19]. ...
... This leads to the second part of the hypothesis. The absolute value of the normal resting membrane potential in tumor cells is much lower than in normal cells, approximately −25 mV compared to approximately −70 mV [18], respectively. Furthermore, when the cell begins to divide, the membrane voltage will drop to roughly −15 mV [19]. ...
Objective:
A theoretical study on the mechanisms through which Tumor Treating Fields (TTFields) affect dividing tumor cells.
Methods:
Numerical analysis was used to revisit two previously proposed mechanisms and introduce a third. We examine the previous hypotheses that: a) TTFields generate a moment that affects microtubule assembly during early mitosis, and b) dielectrophoretic (DEP) forces cause neutral particles to move toward the cleavage furrow during the telophase stage. We further introduce a new hypothesis that TTFields modify cell membrane potential in dividing tumor cells.
Results:
a) The Brownian energy is several orders of magnitude larger than the moment induced by TTFields on tubulin dimers. b) Adding Stokes drag forces to DEP forces shows that the motion of the particles in the cytoplasm is very slow, approximately 0.003 μm/s, and therefore, unless the duration of the telophase is long enough there will be no substantial effect from the DEP forces. c) The Schwan equation shows that electric fields at the frequencies of clinical TTFields can cause a 10% - 17% change in tumor cell membrane potential.
Conclusion:
Our studies find limited support for the previously suggested hypotheses and suggest that the TTFields effect on cell membrane potential by affecting ion channels could be a mechanism of tumor cell death.
Significance:
Previously suggested mechanisms of tumor cell death from TTFields are found lacking. The effect of TTFields on the tumor cell membrane potential warrants further research.
... One mechanism of dysregulation is through bioelectrical changes (1). Tumor cells exhibit a resting membrane potential of approximately −25 mV, significantly lower than that of normal cells (2). Moreover, multiple ion channels are found to be overexpressed in various types of tumor cells (3)(4)(5)(6). ...
Purpose
Currently, a range of electromagnetic therapies, including magnetic field therapy, micro-currents therapy, and tumor treating fields, are under investigation for their potential in central nervous system tumor research. Each of these electromagnetic therapies possesses distinct effects and limitations. Our focus is on overcoming these limitations by developing a novel electric field generator. This generator operates by producing alternating induced currents within the tumor area through electromagnetic induction.
Methods
Finite element analysis was employed to calculate the distribution of electric fields. Cell viability was assessed using the CCK-8 assay. Tumor volumes and weights served as indicators to evaluate the effectiveness of TTIF. The in-vivo imaging system was utilized to confirm tumor growth in the brains of mice.
Results
TTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo.
Conclusion
TTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo. Consequently, TTIF emerges as a potential treatment option for patients with progressive or metastatic GBM.
... Cells have different normal membrane potentials when they are experiencing different physiological changes. For example, when cells are cancerous or dividing, the cell membrane potential will raise to around −25 mV [14] and −15 mV [15] respectively, while the normal cell membrane potential of healthy cell is about −70 mV. The effect of the electromagnetic field induced changes in membrane potential relative to the normal cell membrane resting potential is defined as ...
Objective:
Clinical studies show that low intensity (single V/cm), intermediate-frequency (100 kHz-300 kHz) electric fields inhibit the growth of cancer cells, while the mechanism is not yet understood. We examine the hypothesis that electric fields modify the cell membrane potential of dividing cancer cells in a way that correlates with cells growth inhibition.
Methods:
A Schwan based mathematical model calculates the changes in HeLa cells membrane potential due to single V/cm electric fields and frequencies from 0.1 to 1 MHz. An experimental study examines the effect of these electric fields on the inhibition of HeLa cells growth in an incubator.
Results:
The theoretical calculation shows that the effects of these electric fields on cell membrane potential decrease with an increase in frequency. The HeLa cells experiments verified the inhibitory effect of these fields on cell growth. The inhibitory effect is decreasing with an increase in frequency, in a way that is similar to the frequency dependent effect of these fields on the cell membrane potential.
Conclusions:
The superposition of the theoretical results and the experimental results suggest a correlation between the effect of these fields on the cell membrane potential and inhibition of cancer cell growth. It should be emphasized that correlations do not prove causality, however, they suggest an area for future research.
Significance:
These findings have value for the understanding of the mechanisms of cancer cells growth inhibition with electric fields and suggest an interesting area of research on the interaction between electromagnetic fields and cancer cells.
... In fact the proton shells near surfaces that constitute Pollack's interfacial water configurations [4] display potential differences that are comparable to those attributed to disparities of concentration for potassium and chloride. Quantitative links between plasma membrane physics and quantum-related values have practical applications [5]. ...
Quantitative convergence for solutions involving electron drift velocity, the magnetic A vector and phase shifts reveal an increment of energy in the range of 10-20 J that could relate the Aharanov-Bohm phase modulation of the orbital frequency of a Bohr atom to the electron’s Compton wavelength. The universal persistence of 10-12 W per m2 whose energy applied the square of the hydrogen wavelength solves for the energy equivalence of the rest mass of an electron could set the conditions for excess correlations between electronic systems that produce magnetic fields through optocouplers. Experimental evidence and quantitative solutions indicate variations of the Lorentz Lemma and circularly rotating magnetic fields whose phase and group velocities are uncoupled could create the conditions for excess correlations. Modification of Basharov’s operator of resonance interaction for decoherence and entanglement in the radioactive decay of a diatomic system and Das and Misra’s estimates for the fractal charge of a photon strongly suggests that the efficacy for optocoupler circuits to generate non-local magnetic field effects in living and non-living aqueous systems originates from a single photon wave across the circuit’s p-n junctions. A review of the concepts and data indicate that excess correlations involving photons under optimal conditions are measureable within macrosystems
... The time it takes light to travel a distance of 10 -8 m is approximately 10 -16 s. The relationship between this and the Bohr-orbital rotational time was detailed by Persinger and Lafrenie [45]. This would potentially allow the time-varying phase to be read, or interact with, processes occurring at the level of the Bohr magneton. ...
Here we examine the potential relationship between applied exogenous EMFs and their ability to generate phase-modulations with information carrying capacity. We systematically examine, through dimensional analysis, the potential sources and interactions of these generated phase-modulations. Furthermore, we introduce the concept of time-varying phase modulations through the application of time-varying, amplitude modulated EMFs.
... The quantification developed here suggests that the level of space at which any technology would be focused to initiate the transposition might begin with the dynamics of the cell membrane. We [55] have shown that the ionindependent 26 mV derived from the Nernst equation's constant (set for 310°K or 37°C) is coupled to 4.27·10 -21 J which is the thermal noise limit or kT boundary. It is also associated with the energy associated with the loss or the gain of one bit of information into or from entropy as well as that lost when there is a convergence of operations. ...
I S S N 2 3 4 7-3487 V o l u m e 1 1 , N u m b e r 1 0 J o u r n a l o f A d v a n c e s i n P h y s i c s 4058 | P a g e c o u n c i l f o r I n n o v a t i v e R e s e a r c h J u n e 2016 w w w. c i r w o r l d. c o m ABSTRACT Translation of four dimensional axes anywhere within the spatial and temporal boundaries of the universe would require quantitative values from convergence between parameters that reflect these limits. The presence of entanglement and volumetric velocities indicates that the initiating energy for displacement and transposition of axes would be within the upper limit of the rest mass of a single photon which is the same order of magnitude as a macroscopic Hamiltonian of the modified Schrödinger wave function. The representative metaphor is that any local 4-D geometry, rather than displaying restricted movement through Minkowskian space, would instead expand to the total universal space-time volume before re-converging into another location where it would be subject to cause-effect. Within this transient context the contributions from the anisotropic features of entropy and the laws of thermodynamics would be minimal. The central operation of a fundamental unit of 10-20 J, the hydrogen line frequency, and the Bohr orbital time for ground state electrons would be required for the relocalized manifestation. Similar quantified convergence occurs for the ~10 12 parallel states within space per Planck's time which solve for phase-shift increments where Casimir and magnetic forces intersect. Experimental support for these interpretations and potential applications is considered. The multiple, convergent solutions of basic universal quantities suggest that translations of spatial axes into adjacent spatial states and the transposition of four dimensional configurations any where and any time within the universe may be accessed but would require alternative perspectives and technologies.
Non‐thermal, intermediate frequency (100–500 kHz) electrotherapies present a unique therapeutic strategy to treat malignant neoplasms. Here, pulsed electric fields (PEFs) which induce reversible or irreversible electroporation (IRE) and tumour‐treating fields (TTFs) are reviewed highlighting the foundations, advances, and considerations of each method when applied to glioblastoma (GBM). Several biological aspects of GBM that contribute to treatment complexity (heterogeneity, recurrence, resistance, and blood‐brain barrier(BBB)) and electrophysiological traits which are suggested to promote glioma progression are described. Particularly, the biological responses at the cellular and molecular level to specific parameters of the electrical stimuli are discussed offering ways to compare these parameters despite the lack of a universally adopted physical description. Reviewing the literature, a disconnect is found between electrotherapy techniques and how they target the biological complexities of GBM that make treatment difficult in the first place. An attempt is made to bridge the interdisciplinary gap by mapping biological characteristics to different methods of electrotherapy, suggesting important future research topics and directions in both understanding and treating GBM. To the authors' knowledge, this is the first paper that attempts an in‐tandem assessment of the biological effects of different aspects of intermediate frequency electrotherapy methods, thus offering possible strategies toward GBM treatment.
Significance
Recent evidence from the neuromuscular junction in Drosophila and C. elegans shows that protons are important intercellular signaling molecules operating to modulate presynaptic release or ion channels in adjacent cells. Here, we present evidence that protons also act directly as a nonquantal neurotransmitter in a contemporary amniote to convey excitatory stimuli from type I inner ear vestibular hair cells to their partner postsynaptic calyx nerve terminals. Protonergic neurotransmission works in concert with classical mechanisms and endows this system with a metabolically efficient mechanism to evoke tonic depolarizations of the postsynaptic neuron. Similar intercellular proton signaling mechanisms might be at play in the CNS.
We provide a review of both new experimental and theoretical developments in the Casimir effect. The Casimir effect results from the alteration by the boundaries of the zero-point electromagnetic energy. Unique to the Casimir force is its strong dependence on shape, switching from attractive to repulsive as function of the size, geometry and topology of the boundary. Thus, the Casimir force is a direct manifestation of the boundary dependence of quantum vacuum. We discuss in depth the general structure of the infinities in the field theory which are removed by a combination of zeta-functional regularization and heat kernel expansion. Different representations for the regularized vacuum energy are given. The Casimir energies and forces in a number of configurations of interest to applications are calculated. We stress the development of the Casimir force for real media including effects of nonzero temperature, finite conductivity of the boundary metal and surface roughness. Also, the combined effect of these important factors is investigated in detail on the basis of condensed matter physics and quantum field theory at nonzero temperature. The experiments on measuring the Casimir force are also reviewed, starting first with the older measurements and finishing with a detailed presentation of modern precision experiments. The latter are accurately compared with the theoretical results for real media. At the end of the review we provide the most recent constraints on the corrections to Newtonian gravitational law and other hypothetical long-range interactions at submillimeter range obtained from the Casimir force measurements.
Four B16 melanoma cell variants were investigated to determine if there exists a correlation between their deformability and their metastatic potential. Cell deformability was measured as the percentage of cells traversing 10-mum diameter Nuclepore filter membranes at constant pressure as a function of time. A method was devised to circumvent common problems encountered in cell filtration experiments, i.e., cell aggregation and adhesion to the filter and failure to recover the input. F1a cells with the lowest spontaneous metastatic rate required 44 s for 50% of the cell input to traverse the filter, whereas No. 4 cells, featuring the highest metastatic rate, needed 12 s despite the fact that the cells had identical dimensions. Other variants tested showed intermediate filterability which also correlated with their metastatic potential. Cells, when pretreated with cytochalasin B at a final concentration of 21 microM exhibited increased filterability (75% and 42% greater than control for F1a and No. 4 cells, respectively). Somewhat smaller increases were observed after colchicine treatment. The findings imply major involvement of the cytoskeleton in the filterability and thus deformability of these B16 variants. Such physiochemical factors may play an important role in the metastasis of this and possibly other tumor types.
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