Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity.

Submicrometer magnetic particles, ingested by cells and monitored via the magnetic fields they generate, provide an alternative to optical microscopy for probing movement and viscosity of living cytoplasm, and can be used for cells both in vitro and in vivo. We present methods for preparing lung macrophages tagged with magnetic particles for magnetometric study. Interpretation of the data involves fitting experimental remanent-field decay curves to nonlinear mechanistic models of intracellular particle motion. The model parameters are sensitive to mobility and apparent cytoplasmic viscosity experienced by particle-containing organelles. We present results of parameter estimation for intracellular particle behavior both within control cells and after (a) variable magnetization duration, (b) incubation with cytochalasin D, and (c) particle twisting by external fields. Magnetometric analysis showed cytoplasmic elasticity, dose-dependent motion inhibition by cytochalasin D, and a shear-thinning apparent viscosity.     

Cytoplasmic motions, rheology, and structure probed by a novel magnetic particle method

The motions of magnetic particles contained within organelles of living cells were followed by measuring magnetic fields generated by the particles. The alignment of particles was sensed magnetometrically and was manipulated by external fields, allowing non-invasive detection of particle motion as well as examination of cytoplasmic viscoelasticity. Motility and rheology data are presented for pulmonary macrophages isolated from lungs of hamsters 1 d after the animals had breathed airborne gamma-Fe2O3 particles. The magnetic directions of particles within phagosomes and secondary lysosomes were aligned, and the weak magnetic field produced by the particles was recorded. For dead cells, this remanent field was constant, but for viable macrophages, the remanent field decreased rapidly so that only 42% of its initial magnitude remained 5 min after alignment. A twisting field was applied perpendicular to the direction of alignment and the rate at which particles reoriented to this new direction was followed. The same twisting was repeated for particles suspended in a series of viscosity standards. Based on this approach, the low-shear apparent intracellular viscosity was estimated to be 1.2-2.7 X 10(3) Pa.s (1.2-2.7 X 10(4) poise). Time-lapse video microscopy confirmed the alignment of ingested particles upon magnetization and showed persistent cellular motility during randomization of alignment. Cytochalasin D and low temperature both reduced cytoplasmic activity and remanent-field decay, but affected rheology differently. Magnetic particles were observed in association with the microtubule organizing center by immunofluorescence microscopy; magnetization did not affect microtubule distribution. However, both vimentin intermediate filaments and f-actin reorganized after magnetization. These data demonstrate that magnetometry of isolated phagocytic cells can probe organelle movements, rheology, and physical properties of the cytoskeleton in living cells.     

Analysis of magnetic material in the human heart, spleen and liver

Isothermal remanent magnetization (IRM) acquisition and alternating field (A.F.) demagnetization analyses were performed on human heart, spleen and liver samples resected from cadavers. The magnetic properties of the samples were measured both at 77K and at 273K. A.F. demagnetization was performed at 273K. Results from the analyses of the tissue indicate the presence of ferromagnetic, fine-grained, magnetically interacting particles which, due primarily to magnetic properties, are thought to be magnetite and/or maghemite. The presence of superparamagnetic particles can be inferred from the increase in saturation IRM values when measured at 77K compared with measurements at 273K and the decay of remanent magnetization upon warming from 77K. The concentration of magnetic material (assuming it is magnetite or maghemite) in the samples varies from 13.7 ng g-1 to 343 ng g-1, with the heart tissue generally having the highest concentration. The presence of magnetic material in these organs may have implications for the function of biogenic magnetite in the human body.     

Behavior of magnetic particles in hamster lungs: estimates of clearance and cytoplasmic motility

Ferrimagnetic particles suspended in saline were instilled intratracheally into the lungs of Syrian golden hamsters. The particles were magnetized and aligned by applying an external magnetic field. Upon removal of the external field, the particles produced a remanent magnetic field from the lungs which decayed due to random misalignment of the particles (relaxation). Magnetization and relaxation measurements were performed immediately after instillation, then repeatedly during the first 24 h, and finally at intervals of several days up to 30 days after the instillation. The size of the initial remanent magnetic field immediately following each external magnetization is a measure of the amount of iron oxide in the lungs. It decreased with time, reflecting particle clearance. The rate of relaxation increased steeply during the first 12 h after the instillation and decreased slowly between the 5th and 30th day. Changes in the location of particles from extracellular to intracellular sites and movements from ectoplasmic to endoplasmic sites within cells may be responsible for the observed changes in relaxation rates with time.     

Chains of single-domain magnetite particles in chinook salmon,Oncorhynchus tshawytscha

Summary Although the presence of magnetite in their tissues is correlated with the ability of different species to detect magnetic fields, proof that the magnetite is involved in magnetoreception has not yet been provided. Using the approach employed to localize and isolate magnetic particles in the yellowfin tuna, we found that single-domain magnetite occurs in chains of particles in tissue contained within the dermethmoid cartilage of adult chinook salmon,Oncorhynchus tshawytscha. The particles are present in sufficient numbers to provide the adult fish with a very sensitive magnetoreceptor system. Magnetite in the chinook can be correlated with responses to magnetic fields in a congeneric species, the sockeye salmon. Based on the presence of the chains of particles, we propose behavioral experiments that exploit the responses of sockeye salmon fry to magnetic fields to test explicit predictions of the ferromagnetic magnetoreception hypothesis.     

Comparison of particle clearance and macrophage phagosomal motion in liver and lungs of rats

Magnetic particles and magnetometry were used to noninvasively measure motion of particle-containing organelles in macrophages as well as to monitor the disappearance of particles from tissues. We compared these parameters in the liver (where macrophages are attached to the endothelium) and in the lungs (where macrophages were mobile on epithelial surfaces). Submicrometric magnetic particles were injected intravenously (1.5 mg/kg) into rats; 94% was taken up by the liver. Rats were also instilled intratracheally (1.0 mg/kg) with the same particles. Ultrastructural analyses showed that almost all particles were ingested by macrophages in both organs. Periodically, the retained particles were magnetized and aligned with an external magnet. After the magnet was removed, the decay of the resulting remanent field (relaxation) was followed for 25 min. Relaxation parameters (t1/2 and lambda 0) in the liver were constant from 30 min to 30 days after particle administration, but relaxation in lungs showed a time-dependent increase during the 1st day due to the slower rate of particle phagocytosis. Relaxation in both organs primarily reflects the motion of particle-containing organelles as they are rotated by the cytoskeleton. Relaxation in the lungs may also reflect cell translocation or even changes in alveolar shape. Clearance of particles from the lungs or liver was measured by following B0 (initial magnetic field strength). After correction for growth, the clearance t1/2 was 17.7 and 27.3 days for the lungs and liver, respectively. Bulk transport of particles is probably a more important clearance mechanism in the lungs than in the liver.     

Encouragement of Enzyme Reaction Utilizing Heat Generation from Ferromagnetic Particles Subjected to an AC Magnetic Field

We propose a method of activating an enzyme utilizing heat generation from ferromagnetic particles under an ac magnetic field. We immobilize α-amylase on the surface of ferromagnetic particles and analyze its activity. We find that when α-amylase/ferromagnetic particle hybrids, that is, ferromagnetic particles, on which α-amylase molecules are immobilized, are subjected to an ac magnetic field, the particles generate heat and as a result, α-amylase on the particles is heated up and activated. We next prepare a solution, in which α-amylase/ferromagnetic particle hybrids and free, nonimmobilized chitinase are dispersed, and analyze their activities. We find that when the solution is subjected to an ac magnetic field, the activity of α-amylase immobilized on the particles increases, whereas that of free chitinase hardly changes; in other words, only α-amylase immobilized on the particles is selectively activated due to heat generation from the particles.     

3D Magnetopneumography Magnetic Dipole Model and Its Application Using Fluxgate Gradiometers

Magnetopneumography (MPG) as a non‐invasive method for pneumoconiosis diagnosis has been developed to evaluate the load and spatial distribution of particles within the human lungs through scanning of remanent magnetic fields after magnetization of the subject in a strong direct current field. The measurement of particle spatial distribution is very important for pneumoconiosis diagnosis because localized deposits may be associated with some pathological changes such as pulmonary fibrosis. Previous research found that loads of magnetite particles were proportional to their magnetic dipole moments. The three‐dimensional (3D) MPG magnetic dipole model (MDM) proposed in this paper and based on Biot–Savart Law and matrix manipulation provides a means of precise measurement of the particle distribution and load amount. A styrofoam + magnetite powder phantom with magnetization was laid on a nonmagnetic board. Two first‐order fluxgate gradiometers with 10^–12 T sensitivity were coaxially applied over and under the phantom and used for scanning remanent magnetic fields. This paper provides validation results using 3D MPG MDM through two experiments. The overall error of the simulation results is 0.2–2.7% in the center and 7.28–9.42% in the corners of the subject. Finally, this paper gives clinical experiments with a welder suffering stage‐II pneumoconiosis and states that the 3D MPG MDM shows similar results to X‐ray chest films in pneumoconiosis diagnosis. The results suggest that the 3D MPG MDM is potentially a reasonable and accurate algorithmic model to inversely track the load amount and distribution of magnetite particles within the lungs. Bioelectromagnetics. 2019;40:472–487. © 2019 Wiley Periodicals, Inc     

Development of Cellular Magnetic Dipoles in Magnetotactic Bacteria

Magnetotactic bacteria benefit from their ability to form cellular magnetic dipoles by assembling stable single-domain ferromagnetic particles in chains as a means to navigate along Earth's magnetic field lines on their way to favorable habitats. We studied the assembly of nanosized membrane-encapsulated magnetite particles (magnetosomes) by ferromagnetic resonance spectroscopy using Magnetospirillum gryphiswaldense cultured in a time-resolved experimental setting. The spectroscopic data show that 1), magnetic particle growth is not synchronized; 2), the increase in particle numbers is insufficient to build up cellular magnetic dipoles; and 3), dipoles of assembled magnetosome blocks occur when the first magnetite particles reach a stable single-domain state. These stable single-domain particles can act as magnetic docks to stabilize the remaining and/or newly nucleated superparamagnetic particles in their adjacencies. We postulate that docking is a key mechanism for building the functional cellular magnetic dipole, which in turn is required for magnetotaxis in bacteria.     

Numerical evaluation of the fields induced by body motion in or near high-field MRI scanners

In modern magnetic resonance imaging , both patients and health care workers are exposed to strong, non-uniform static magnetic fields inside and outside of the scanner, in which body movement may be able to induce electric currents in tissues which could be potentially harmful. This paper presents theoretical investigations into the spatial distribution of induced E-fields in a tissue-equivalent human model when moving at various positions around the magnet. The numerical calculations are based on an efficient, quasi-static, finite-difference scheme. Three-dimensional field profiles from an actively shielded 4 T magnet system are used and the body model projected through the field profile with normalized velocity. The simulation shows that it is possible to induce E-fields/currents near the level of physiological significance under some circumstances and provides insight into the spatial characteristics of the induced fields. The methodology presented herein can be extrapolated to very high field strengths for the evaluation of the effects of motion at a variety of field strengths and velocities.     

Deformation of intracellular endosomes under a magnetic field

We present a non-invasive method to monitor the membrane tension of intracellular organelles using a magnetic field as an external control parameter. By exploiting the spontaneous endocytosis of anionic colloidal ferromagnetic nanoparticles, we obtain endosomes possessing a superparamagnetic lumen in eukaryotic cells. Initially flaccid, the endosomal membrane undulates because of thermal fluctuations, restricted in zero field by the resting tension and the curvature energy of the membrane. When submitted to a uniform magnetic field, the magnetized endosomes elongate along the field, resulting in the flattening of the entropic membrane undulations. The quantification of the endosome deformation for different magnetic fields allows in situ measurement of the resting tension and the bending stiffness of the membrane enclosing the intracellular organelle.     

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.     

Efficient DNA ligation by selective heating of DNA ligase with a radio frequency alternating magnetic field

We present a simple method for efficient DNA ligation utilizing the heat generation of ferromagnetic particles subjected to an ac magnetic field. We carry out the ligation of DNA fragments with cohesive ends using T4 DNA ligase immobilized on the surface of ferromagnetic particles. When a radio frequency alternating magnetic field is applied, ferromagnetic particles dissipate heat and DNA ligase on the particles is selectively heated up and activated with little influence on the annealing of DNA ends, as a result of which the ligation efficiency increases. We show that the ligation efficiency increases with an increase in the field amplitude.     

Physical interactions of static magnetic fields with living tissues

Clinical magnetic resonance imaging (MRI) was introduced in the early 1980s and has become a widely accepted and heavily utilized medical technology. This technique requires that the patients being studied be exposed to an intense magnetic field of a strength not previously encountered on a wide scale by humans. Nonetheless, the technique has proved to be very safe and the vast majority of the scans have been performed without any evidence of injury to the patient. In this article the history of proposed interactions of magnetic fields with human tissues is briefly reviewed and the predictions of electromagnetic theory on the nature and strength of these interactions are described. The physical basis of the relative weakness of these interactions is attributed to the very low magnetic susceptibility of human tissues and the lack of any substantial amount of ferromagnetic material normally occurring in these tissues. The presence of ferromagnetic foreign bodies within patients, or in the vicinity of the scanner, represents a very great hazard that must be scrupulously avoided. As technology and experience advance, ever stronger magnetic field strengths are being brought into service to improve the capabilities of this imaging technology and the benefits to patients. It is imperative that vigilance be maintained as these higher field strengths are introduced into clinical practice to assure that the high degree of patient safety that has been associated with MRI is maintained.     

Quantitative Modeling and Optimization of Magnetic Tweezers

Magnetic tweezers are a powerful tool to manipulate single DNA or RNA molecules and to study nucleic acid-protein interactions in real time. Here, we have modeled the magnetic fields of permanent magnets in magnetic tweezers and computed the forces exerted on superparamagnetic beads from first principles. For simple, symmetric geometries the magnetic fields can be calculated semianalytically using the Biot-Savart law. For complicated geometries and in the presence of an iron yoke, we employ a finite-element three-dimensional PDE solver to numerically solve the magnetostatic problem. The theoretical predictions are in quantitative agreement with direct Hall-probe measurements of the magnetic field and with measurements of the force exerted on DNA-tethered beads. Using these predictive theories, we systematically explore the effects of magnet alignment, magnet spacing, magnet size, and of adding an iron yoke to the magnets on the forces that can be exerted on tethered particles. We find that the optimal configuration for maximal stretching forces is a vertically aligned pair of magnets, with a minimal gap between the magnets and minimal flow cell thickness. Following these principles, we present a configuration that allows one to apply ≥40 pN stretching forces on ≈1-μm tethered beads.     

Phagocytic and motile properties of endothelial cells measured magnetometrically: effects of endotoxin

Endothelial cells lining the vasculature share some properties with macrophages and neutrophils in that they can take up material from the blood and are known to migrate, particularly during wound healing. We observed that endothelial cells isolated from bovine pulmonary arteries ingested magnetic iron oxide particles during culture in vitro. Using a non-optical, magnetometric method, we examined motions of magnetic-particle containing intracellular vacuoles. We demonstrated that these organelles move within endothelial cells, but at a slower rate than phagosomes within macrophages. Magnetometry was used to show that incubation with endotoxin (10 micrograms/ml) for 4 hr resulted in a decrease in cytoplasmic movement; yet the fluidity of the cytoplasm was increased, as measured by intracellular particle response to forced motion. We conclude that intracellular magnetic probe particles can detect vesicular motion in endothelial cells, and that endotoxin exposure can affect endothelial cells directly, altering their physical properties; these alterations precede ultrastructural evidence of cell death.     

Combined action of static and alternating magnetic fields on ion motion in a macromolecule: Theoretical aspects

This is an attempt to solve the energetic problem of the primary detection of weak parallel static (DC) and alternating (AC) extremely low frequency (ELF) magnetic fields. We studied the equations of motion for an ion situated inside a macromolecule under the influence of these fields. The main concern is with the magnetic field influence on thermal motion of the ion in the macromolecule. The resonance effects are revealed at discrete frequencies of the ion thermal oscillations determined by the DC field magnitude and the AC field frequency. These phenomena result from the Larmor precession of the ion thermal motion. When the DC field or, to a greater extent, the combined DC and AC fields with the specific frequencies are turned on or cut off, changes occur in the energy of the ion thermal motion. If, inside the macromolecule, the ion is sufficiently protected against immediate impacts of particles of the medium surrounding the macromolecule, these changes may be enough to trigger alteration in the quantum state of the macromolecule. Bioelectromagnetics 19:279–292, 1998. © 1998 Wiley-Liss, Inc.     

电磁场曝露对生物组织电磁特性的影响

电磁辐射严重影响着人体的健康.电磁场生物效应的发生机制与电磁场本身的特性相关,同时也与生物组织在电磁场作用下电磁特性的改变密切相关.生物体内的信号分子、自由基以及磁颗粒等处于外加电磁场中时其电磁特性会发生变化,尤其是不同频率电磁场曝露作用下生物组织的导电、介电以及磁学等特性会有非常显著的区别.明确不同频率电磁场作用下生物组织电磁特性的变化规律是研究电磁场生物效应发生机制以及预防问题的关键.综述了近年来电磁场对于生物组织电磁特性影响的研究成果,并对未来的研究方向做了展望.     

Bat head contains soft magnetic particles: Evidence from magnetism

Recent behavioral observations have indicated that bats can sense the Earth's magnetic field. To unravel the magnetoreception mechanism, the present study has utilized magnetic measurements on three migratory species (Miniopterus fuliginosus, Chaerephon plicata, and Nyctalus plancyi) and three non‐migratory species (Hipposideros armiger, Myotis ricketti, and Rhinolophus ferrumequinum). Room temperature isothermal remanent magnetization acquisition and alternating‐field demagnetization showed that the bats' heads contain soft magnetic particles. Statistical analyses indicated that the saturation isothermal remanent magnetization of brains (SIRM_{1T_brain}) of migratory species is higher than those of non‐migratory species. Furthermore, the SIRM_{1T_brain} of migratory bats is greater than their SIRM_{1T_skull}. Low‐temperature magnetic measurements suggested that the magnetic particles are likely magnetite (Fe₃O₄). This new evidence supports the assumption that some bats use magnetite particles for sensing and orientation in the Earth's magnetic field. Bioelectromagnetics 31:499–503, 2010. © 2010 Wiley‐Liss, Inc.     

Anisotropy of Bullet-Shaped Magnetite Nanoparticles in the Magnetotactic Bacteria Desulfovibrio magneticus sp. Strain RS-1

Magnetotactic bacteria (MTB) build magnetic nanoparticles in chain configuration to generate a permanent dipole in their cells as a tool to sense the Earth’s magnetic field for navigation toward favorable habitats. The majority of known MTB align their nanoparticles along the magnetic easy axes so that the directions of the uniaxial symmetry and of the magnetocrystalline anisotropy coincide. Desulfovibrio magneticus sp. strain RS-1 forms bullet-shaped magnetite nanoparticles aligned along their (100) magnetocrystalline hard axis, a configuration energetically unfavorable for formation of strong dipoles. We used ferromagnetic resonance spectroscopy to quantitatively determine the magnetocrystalline and uniaxial anisotropy fields of the magnetic assemblies as indicators for a cellular dipole with stable direction in strain RS-1. Experimental and simulated ferromagnetic resonance spectral data indicate that the negative effect of the configuration is balanced by the bullet-shaped morphology of the nanoparticles, which generates a pronounced uniaxial anisotropy field in each magnetosome. The quantitative comparison with anisotropy fields of Magnetospirillum gryphiswaldense, a model MTB with equidimensional magnetite particles aligned along their (111) magnetic easy axes in well-organized chain assemblies, shows that the effectiveness of the dipole is similar to that in RS-1. From a physical perspective, this could be a reason for the persistency of bullet-shaped magnetosomes during the evolutionary development of magnetotaxis in MTB.