Energetic constraints on the creation of cell membrane pores by magnetic particles.

Naturally occurring and contaminant ferromagnetic and ferrimagnetic particles have been found within or near cells, and might allow pulsed magnetic fields to create transient cell membrane opening ("pores"). We show that this possibility is significantly constrained by the maximum rotational energy that can be transferred to the cell membrane. For single biologically synthesized magnetosomes (radius rmag approximately 10(-7) m, magnetic moment mu approximately 2 x 10(-15) A m2) and typical cell membranes, the estimated pulse magnitude must exceed Bo approximately 6 x 10(-3) to 7 x 10(-2) T, and the optimal pulse durations are in the range 10(-5) s < tpulse < 10(-1) s. For larger contaminant particles with larger net magnetic moments, the pulse magnitudes could be only somewhat smaller, and the optimal durations are about the same. Very large pulses that exceed the coercive force of a particle are predicted to have a smaller effective magnitude and shorter effective duration.     

超低频脉冲磁场诱导癌细胞凋亡机理研究

我们研究超低频脉冲磁场(峰值0.6~2.0T,梯度10~100T.m-1,脉冲宽度20~200ms,重复频率0.16~1.34HZ)作用于鼠S-180肉瘤。在电镜下观察到肉瘤细胞程序性死亡的许多特征。这一磁场引起约1.5mv的跨膜电位变化,导致钙离子Ca2+内流,促使癌细胞凋亡。磁场对运动电荷的洛仑兹力使运动的带电粒子束缚在拉莫尔(Larmor)半径以内,影响正负带电离子对细胞膜和核膜的渗透能力,甚至在膜上形成空洞。     

The Influence of a gradient static magnetic field on an unstirred Belousov-Zhabotinsky reaction

It is believed that static magnetic fields (SMF) cannot affect the pattern formation of the Belousov-Zhabotinsky (BZ) reaction, which has been frequently studied as a simplified experimental model of a nonequilibrium open system, because SMF produces no induced current and the magnetic force of SMF far below 1 T is too low to expect the effects on electrons in the BZ reaction. In the present study, we examined whether the velocity of chemical waves in the unstirred BZ reaction can be affected by a moderate-intensity SMF exposure depending on the spatial magnetic gradient. The SMF was generated by a parallel pair of attracting rectangular NdFeB magnets positioned opposite each other. The respective maximum values of magnetic flux density (B(max)), magnetic flux gradient (G(max)), and the magnetic force product of the magnetic flux density its gradient (a magnetic force parameter) were 206 mT, 37 mT/mm, and 3,000 mT(2)/mm. The ferroin-catalyzed BZ medium was exposed to the SMF for up to 16 min at 25 degrees C. The experiments demonstrated that the wave velocity was significantly accelerated primarily by the magnetic gradient. The propagation of the fastest wave front indicated a sigmoid increase along the peak magnetic gradient line, but not along the peak magnetic force product line. The underlying mechanisms of the SMF effects on the anomalous wave propagation could be attributed primarily to the increased concentration gradient of the paramagnetic iron ion complexes at the chemical wave fronts induced by the magnetic gradient.     

The trajectories of particles suspended in electrolytes under the influence of crossed electric and magnetic fields

We observed that particles, suspended in an electrolyte and brought into crossed magnetic and electric fields of low intensities, will deviate in the central part of the electrophoresis chamber of a standard Zeiss Cytopherometer with a component vertical to both fields. The direction and magnitude, however, were sharply at variance with what would be expected by the action of the Lorentz force (EMF) on the surface of the particles. The magnitude of the deviation depends upon the magnetic and electric field strength, the ion concentration of the suspension medium and the geometry of the chamber. The movement of the particles is due to streaming of the electrolyte which is mainly caused by inhomogeneities of the electric field in the electrophoresis chamber. The magnitude of the effect is high enough to occur under physiological conditions. Magneto-electrophoretic streaming might eventually act as a transducer mechanism which could explain the ability of some animals to orientate themselves in the geomagnetic field.     

The trajectories of particles suspended in electrolytes under the influence of crossed electric and magnetic fields. Possible explanation of the sensitivity of organism to magnetic fields

We observed that particles, suspended in an electrolyte and brought into crossed magnetic and electric fields of low intensities, will deviate in the central part of the electrophoresis chamber of a standard Zeiss Cytopherometer with a component vertical to both fields. The direction and magnitude, however, were sharply at variance with what would be expected by the action of the Lorentz force (EMF) on the surface of the particles. The magnitude of the deviation depends upon the magnetic and electric field strength, the ion concentration of the suspension medium and the geometry of the chamber. The movement of the particles is due to streaming of the electrolyte which is mainly caused by inhomogeneities of the electric field in the electrophoresis chamber. The magnitude of the effect is high enough to occur physiological conditions. Magneto-electrophoretic streaming might eventually act as a transducer mechanism which could explain the ability of some animals to orientate themselves in the geomagnetic field.     

Electromagnetic gating in ion channels.

There have been many attempts to develop a theoretical explanation of the phenomena of electromagnetic field interactions with biological systems. None of the reported efforts have been entirely successful in accounting for the observed experimental results, in particular with respect to the reports of interactions between extremely low frequency (ELF) magnetic fields and biological systems at ion cyclotron resonance frequencies. The approach used in this paper starts with the Lorentz force equation, but use is made of cylindrical co-ordinates and cylindrical boundary conditions in an attempt to more closely model the walls of an ion channel. The equations of motion of an ion that result from this approach suggest that the inside shape of the channel plus the ELF magnetic fields at specific frequencies and amplitudes could act as a gate to control the movement of the ion across the cell membrane.     

Diffusion of water in the endosperm tissue of wheat grains as studied by pulsed field gradient nuclear magnetic resonance.

Pulsed field gradient nuclear magnetic resonance has been used to measure water self-diffusion coefficients in the endosperm tissue of wheat grains as a function of the tissue water content. A model that confines the water molecules to a randomly oriented array of capillaries with both transverse dimension less than 100 nm has been used to fit the data and give a unique diffusion coefficient at each water content. The diffusion rates vary from 1.8 x 10(-10) m2s-1 at the lowest to 1.2 x 10(-9) m2s-1 at the highest moisture content. This variation can be explained in terms of an increase in water film thickness from approximately 0.5 to approximately 2.5 nm over the moisture range investigated (200-360 mg g-1).     

The electromechanics of DNA in a synthetic nanopore

We have explored the electromechanical properties of DNA on a nanometer-length scale using an electric field to force single molecules through synthetic nanopores in ultrathin silicon nitride membranes. At low electric fields, E < 200 mV/10 nm, we observed that single-stranded DNA can permeate pores with a diameter >/=1.0 nm, whereas double-stranded DNA only permeates pores with a diameter >/=3 nm. For pores <3.0 nm diameter, we find a threshold for permeation of double-stranded DNA that depends on the electric field and pH. For a 2 nm diameter pore, the electric field threshold is approximately 3.1 V/10 nm at pH = 8.5; the threshold decreases as pH becomes more acidic or the diameter increases. Molecular dynamics indicates that the field threshold originates from a stretching transition in DNA that occurs under the force gradient in a nanopore. Lowering pH destabilizes the double helix, facilitating DNA translocation at lower fields.     

Myotube orientation using strong static magnetic fields

In this experiment, we evaluated the effects of strong static magnetic fields (SMF) on the orientation of myotubes formed from a mouse-derived myoblast cell line, C2C12. Myogenic differentiation of C2C12 cells was conducted under exposure to SMF at a magnetic flux density of 0-10 T and a magnetic gradient of 0-41.7 T/m. Exposure to SMF at 10 T led to significant formation of oriented myotubes. Under the high magnetic field gradient and a high value of the product of the magnetic flux density and magnetic field gradient, myotube orientation increased as the myogenic differentiation period increased. At the 3 T exposure position, where there was a moderate magnetic flux density and moderate magnetic field gradient, myotube orientation was not observed. We demonstrated that SMF induced the formation of oriented myotubes depending on the magnetic flux density, and that a high magnetic field gradient and a high value of the product of the magnetic flux density and magnetic field gradient induced the formation of oriented myotubes 6 days after myogenic differentiation. We did not detect any effect of the static magnetic fields on myogenic differentiation or cell number. To the best of our knowledge, this is the first report to demonstrate that myotubes orient to each other under a SMF without affecting the cell number and myogenic differentiation.     

Modulation of salt permeabilities of intestinal brush-border membrane vesicles by micromolar levels of internal calcium

A possible modulation of ion permeabilities of rat intestinal brush-border membrane vesicles by Ca2+, a putative second messenger of salt secretion, was explored by three independent methods: (1) measurements of [3H]glucose accumulation driven by a Na+ gradient; (2) stopped-flow spectrophotometry of salt-induced osmotic swelling; (3) 86Rb+, 22Na+ and 36Cl- flux measurements. Cytoskeleton-deprived membrane vesicles were prepared from isolated brushborders by thiocyanate treatment. Intravescicular Ca2+ levels were varied by preincubating vesicles in Ca-EGTA buffers in the presence of the Ca2+-ionophore A23187. At Ca2+free greater than 10(-5) M, initial Na+-dependent glucose uptake in the presence of a 0.1 M NaSCN gradient (but not in its absence) was inhibited by about 50 per cent as compared to EGTA alone (ED50 approximately equal to 10(-6) M Ca2+). By contrast, initial rates of 22Na+ uptake and reswelling rates of vesicles exposed to a NaSCN gradient were increased at least 2-fold by 10(-5) M Ca2+free. Both observations are compatible with a Ca2+-induced increase of the Na+-permeability of the vesicle membrane. The modulation of ion transport was fully reversible and critically dependent on internal Ca2+, suggesting a localization of Ca2+-sensor sites at the inner surface of the microvillous membrane. As shown by radiotracer and osmotic swelling measurements, micromolar Ca2+ additionally increased the flux rate of K+, Rb+, Cl- and NO-3 but did not change the membrane permeability for small uncharged molecules, including glucose and mannitol. The effect of Ca2+ on ion permeabilities could be blocked by Ba2+ (10(-3) M) or Mg2+ (10(-2) M), but not by amiloride (10(-3) M), apamin (2 X 10(-7) M), trifluoperazine (10(-4) M) or quinine (5 X 10(-4) M). At present it is unclear whether Ca2+ activates a nonselective cation and anion channel or multiple highly selective channels in the vesicle membrane.     

Axonal surface charges: evidence for phosphate structure.

The effect of different extracellular alkaline-earth cations (Ca2+, Mg2+, Sr2+, Ba2+) upon the threshold membrane potential for spike initiation in crayfish axon has been studied by means of intracellular microelectrodes. This was done at the following extracellular concentrations of the divalent uranyl ion (UO2/2+): 1.0 X 10(-6) M, 3.0 X 10(-6) M, and 9.0 X 10(-6) M. At each concentration employed, extensive neutralization of axonal surface charges by UO2/2+ was evidenced by the fact that equal concentrations (50 mM) of alkaline-earth cations did not have the same effect on the threshold potential. The selectivity sequences observed at the different uranyl-ion concentrations were: 1.0 X 10(-6) M UO2/2+, Ca2+ greater than Mg2+ greater than Sr2+ greater than Ba2+; 3.0 X 10(-6) M UO2/2+, Ca2+ greater than Mg2+ greater than Ba2+ larger than or equal to Sr2+; 9.0 X 10(-6) M UO2/2+, Ca2+ approximately Ba2+ greater than Sr2+ greater than Mg2+. These selectivity sequences are in accord with the equilibrium selectivity theory for alkaline-earth cations. At each of the concentrations used, uranyl ion did not have any detectable effect on the actual shape of the action potential itself. It is concluded that many (if not most) of the surface acidic groups in the region of the sodium gates represent phosphate groups of membrane phospholipids, but that the m gates themselves are probably protein-aceous in structure.     

Thermoregulation in rodents exposed to high-intensity stationary magnetic fields

Rectal temperatures were recorded in mice and rats during exposure to a stationary 7.55 Tesla (1 T = 10(4) Gauss) homogeneous magnetic field, and to magnetic field gradients ranging from 58.1 - 58.6 T/m. Contrary to observations reported recently by other investigators, no evidence was found for a change in the body temperature of rodents exposed to strong homogeneous or gradient magnetic fields.     

Theoretical limits on the threshold for the response of long cells to weak extremely low frequency electric fields due to ionic and molecular flux rectification.

Understanding exposure thresholds for the response of biological systems to extremely low frequency (ELF) electric and magnetic fields is a fundamental problem of long-standing interest. We consider a two-state model for voltage-gated channels in the membrane of an isolated elongated cell (Lcell = 1 mm; rcell = 25 micron) and use a previously described process of ionic and molecular flux rectification to set lower bounds for a threshold exposure. A key assumption is that it is the ability of weak physical fields to alter biochemistry that is limiting, not the ability of a small number of molecules to alter biological systems. Moreover, molecular shot noise, not thermal voltage noise, is the basis of threshold estimates. Models with and without stochastic resonance are used, with a long exposure time, texp = 10(4) s. We also determined the dependence of the threshold on the basal transport rate. By considering both spherical and elongated cells, we find that the lowest bound for the threshold is Emin approximately 9 x 10(-3) V m-1 (9 x 10(-5) V cm-1). Using a conservative value for the loop radius rloop = 0.3 m for induced current, the corresponding lower bound in the human body for a magnetic field exposure is Bmin approximately 6 x 10(-4) T (6 G). Unless large, organized, and electrically amplifying multicellular systems such as the ampullae of Lorenzini of elasmobranch fish are involved, these results strongly suggest that the biophysical mechanism of voltage-gated macromolecules in the membranes of cells can be ruled out as a basis of possible effects of weak ELF electric and magnetic fields in humans.     

细胞离子在振荡电磁场作用下的受力模型分析

本文通过生物细胞模型,研究振荡电场、振荡磁场以及振荡磁场产生的感应电场对细胞离子的作用机理。模型分析结果表明,电场力和罗仑兹力对细胞膜两侧的自由离子将产生加速度,振荡离子将产生周期性电位移。该模型同时也解释了脉冲电磁场比同参教的连续场产生更多的生物效应,以及连续场在开始施加和切除时的效应最大。     

Effect of thyroid hormone receptors in normal and cancerous cells on the ionic conductivity of bilayer phospholipid membranes

The effect of thyroid hormones receptors isolated from normal and cancer cells on bilayer phospholipid membranes (BPhLM) conductivity, has been studied. The receptor isolated from normal cells in complex X with the hormone selectively induces H+-conductivity of BPhLM generating transmembrane potential equal to 42 mV on the membrane at pH gradient equal to 1. In the presence of K+, Na+, Ca+, Mn2+, Sr2+, Mg2+ the changes of BPhLM are not observed. Neither hormones (T3, T4) nor receptor in free position affect the BPhLM conductivity. Thyroid hormone receptor isolated from mamalignantly transformed cells in a complex with T3 or T4 increases the BPhLM permeability for Ca2+. The transmembrane potential measured at 10fold Ca2+ ion concentration is equal to 16 mV. In the presence of H+, K+, Na+, Mn2+, Sr2+, Mg2+, Ba2+, the resistance of BPhLM doesn't change.     

Large gradient high magnetic field affects the association of MACF1 with actin and microtubule cytoskeleton

The intense inhomogeneous magnetic fields acting on the diamagnetic materials naturally present in cells can generate strong magnetic forces. We have developed a superconducting magnet platform with large gradient high magnetic field (LG‐HMF), which can produce three magnetic force fields of ?1360, 0, and 1312 T²/m, and three corresponding apparent gravity levels, namely 0, 1, and 2‐g for diamagnetic materials. In this study, the effects of different magnetic force fields on osteoblast‐like cells (MG‐63 and MC3T3‐E1) viability, microtubule actin crosslinking factor 1 (MACF1) expression and its association with cytoskeleton were investigated. Results showed that cell viability increased to different degrees after exposure to 0 or 1‐g conditions for 24 h, but it decreased by about 30% under 2‐g conditions compared with control conditions. An increase in MACF1 expression at the RNA or protein level was observed in osteoblast‐like cells under the magnetic force field of ?1360 T²/m (0‐g) relative to 1312 T²/m (2‐g). Under control conditions, anti‐MACF1 staining was scattered in the cytoplasm and partially colocalized with actin filaments (AFs) or microtubules (MTs) in the majority of osteoblast‐like cells. Under 0‐g conditions, MACF1 labeling was concentrated at perinuclear region and colocalization was not apparent. The patterns of anti‐MACF1 labeling on MTs varied with MTs' changing under LG‐HMF environment. In conclusion, LG‐HMF affects osteoblast‐like cell viability, MACF1 distribution, expression, and its association with cytoskeleton to some extent. Bioelectromagnetics 30:545–555, 2009. © 2009 Wiley‐Liss, Inc.     

A Lorentz model for weak magnetic field bioeffects: Part I—Thermal noise is an essential component of AC/DC effects on bound ion trajectory

We have previously employed the Lorentz–Langevin model to describe the effects of weak exogenous magnetic fields via the classical Lorentz force on a charged ion bound in a harmonic oscillator potential, in the presence of thermal noise forces. Previous analyses predicted that µT‐range fields give rise to a rotation of the oscillator orientation at the Larmor frequency and bioeffects were based upon the assumption that the classical trajectory of the bound charge itself could modulate a biochemical process. Here, it is shown that the thermal component of the motion follows the Larmor trajectory. The results show that the Larmor frequency is independent of the thermal noise strength, and the motion retains the form of a coherent oscillator throughout the binding lifetime, rather than devolving into a random walk. Thermal equilibration results in a continual increase in the vibrational amplitude of the rotating oscillator towards the steady‐state amplitude, but does not affect the Larmor orbit. Thus, thermal noise contributes to, rather than inhibits, the effect of the magnetic field upon reactivity. Expressions are derived for the ensemble average of position and the velocity of the thermal component of the oscillator motion. The projection of position and velocity onto a Cartesian axis measures the nonuniformity of the Larmor trajectory and is illustrated for AC and combined AC/DC magnetic fields, suggesting a means of interpreting resonance phenomena. It is noted that the specific location and height of resonances are dependent upon binding lifetime and initial AC phase. Bioelectromagnetics 30:462–475, 2009. © 2009 Wiley‐Liss, Inc.     

Detection of intracellular macromolecule behavior under strong magnetic fields by linearly polarized light

Strong static magnetic fields on the order of 10 T have a diamagnetic force on cell components and generate a clear alignment of a smooth muscle cell assembly, parallel to the direction of the magnetic fields within an exposure period of 3 days. This work shows the effects of diamagnetic torque forces on cell component motion. Linearly polarized light was utilized to detect the displacement of intracellular macromolecules. The polarized light passed through a mass of cells in a magnetic field, and transmission of the light increased and reached a plateau 2 h after the beginning of magnetic field exposure at 14 T. However, no distinct change was observed in transmission of the light under zero magnetic field exposure. The change in polarized light intensity through the lamellar cell assembly under magnetic fields corresponds to behavioral changes in cell components. It was speculated that intracellular macromolecules rotated and showed a displacement due to diamagnetic torque forces during 2-3 h of magnetic field exposure at 14 T.     

Spatial gradient effects of 120 mT static magnetic field on endothelial tubular formation in vitro

This study investigated the spatial magnetic gradient effects of static magnetic fields (SMF) on endothelial tubular formation by applying the maximum spatial gradient to a target site of culture wells for cell growth. The respective maximum values of magnetic flux density (B(max)), magnetic flux gradient (G(max)) and the magnetic force product of the magnetic flux density and its gradient (a parameter of magnetic force) were 120 mT, 28 mT/mm and 1428 mT(2)/mm. The effects of gradient SMF on tubular formation were compared with those of uniform SMF that has no spatial gradients on the entire bottom area of culture wells. Five experimental groups of 25 samples each were examined: (1) sham exposure (control); (2) peak gradient exposure in the peripheral part; (3) peak gradient exposure in the central part; (4) uniform exposure to 20 mT; (5) uniform exposure to 120 mT. The SMF or sham exposure was carried out for 10 days. Photomicrographs of tubular cells, immunostained with an anti-platelet-endothelial cell adhesion molecule-1 (PECAM-1 [CD31]) antibody as a pan-endothelial marker, were analyzed after the 10-day culture. Gradient SMF in the peripheral or central part was found to significantly promote tubular formation in terms of the area density and length of tubules in each peak gradient/force part of the wells, compared with the sham exposure. In contrast, uniform SMF did not induce any significant change in the tubular formation. These findings suggest that tubule formation can be promoted by applying the peak gradient/force to a target site of culture wells.     

Modulation of the shape and speed of a chemical wave in an unstirred Belousov–Zhabotinsky reaction by a rotating magnet

The objective of this study was to observe whether a rotating magnetic field (RMF) could change the anomalous chemical wave propagation induced by a moderate‐intensity gradient static magnetic field (SMF) in an unstirred Belousov–Zhabotinsky (BZ) reaction. The application of the SMF (maximum magnetic flux density = 0.22 T, maximum magnetic flux density gradient = 25.5 T/m, and peak magnetic force product (flux density × gradient) = 4 T²/m) accelerated the propagation velocity in a two‐dimensional pattern. Characteristic anomalous patterns of the wavefront shape were generated and the patterns were dependent on the SMF distribution. The deformation and increase in the propagation velocity were diminished by the application of an RMF at a rotation rate of 1 rpm for a few minutes. Numerical simulation by means of the time‐averaged value of the magnetic flux density gradient or the MF gradient force over one rotation partially supported the experimental observations. These considerations suggest that RMF exposure modulates the chemical wave propagation and that the degree of modulation could be, at least in part, dependent on the time‐averaged MF distribution over one rotation. Bioelectromagnetics 34:220–230, 2013. © 2012 Wiley Periodicals, Inc.