Search

Tissues are generally subjected to external stresses, a potential stimulus for their differentiation or remodeling. While single-cell rheology has been extensively studied leading to controversial results about nonlinear response, mechanical tissue behavior under external stress is still poorly understood, in particular, the way individual cell properties translate at the tissue level. Herein, using magnetic cells we were able to form perfectly monitored cellular aggregates (magnetic molding) and to deform them under controlled applied stresses over a wide range of timescales and amplitudes (magnetic rheometer). We explore the rheology of these minimal tissue models using both standard assays (creep and oscillatory response) as well as an innovative broad spectrum solicitation coupled with inference analysis thus being able to determine in a single experiment the best rheological model. We find that multicellular aggregates exhibit a power-law response with nonlinearities leading to tissue stiffening at high stress. Moreover, we reveal the contribution of intracellular (actin network) and intercellular components (cell-cell adhesions) in this aggregate rheology.

Stimuli-responsive compartments are attracting more and more attention through the years motivated by their wide applications in different fields including encapsulation, manipulation, and triggering of chemical reactions on demand. Among others, magnetic responsive compartments are particularly attractive due to the numerous advantages of magnetic fields compared to other external stimuli. In this article, we used an oil-based ferrofluid where the magnetic nanoparticles have been coated with different polymers to increase their amphiphilic character and surface activity, consequently rendering the interface magnetically responsive. Microliter aqueous nonmagnetic droplets dispersed in the oil-based ferrofluid were used as a model of microreactors. A comprehensive experimental and theoretical study of the deformation, attraction, and coalescence processes of the nonmagnetic water droplets coated with the magnetic nanoparticles under an applied magnetic field in the continuous oil-based ferrofluid phase is provided. To manipulate the packing of the nanoparticles at the water/oil interface, the ionic strength of the aqueous droplets was varied using different NaCl concentrations, and its effect on modulating the coalescence of the droplets was probed. Our results show that the water droplets deform along the magnetic field depending on the magnetic properties of the ferrofluid itself and on the surface properties of the interface, attract in pairs under the action of the magnetic dipole force, and coalesce by the action of the same force with a stochastic behavior. We have studied all of these phenomena as a function of the magnetic field applied, evaluating in each case the forces and/or pressures acting on the droplets with particular attention to roles of magnetic attraction, interface properties, and viscosity in the system. This work offers an overall set of tools to understand and predict the behavior of multiple water droplets in an oil-based ferrofluid for lab-on-a-chip applications.

We report the first quantitative measurements of the resonance frequencies of a torus of fluid confined in a horizontal Hele-Shaw cell. By using the unwetting property of a metal liquid, we are able to generate a stable torus of fluid with an arbitrary aspect ratio. When subjected to vibrations, the torus displays azimuthal patterns at its outer periphery. These lobes oscillate radially, and their number n depends on the forcing frequency. We report the instability "tongues" of the patterns up to n=25. These resonance frequencies are well explained by adapting to a fluid torus the usual drop model of Rayleigh. This approach could be applied to the modeling of large-scale structures arisen transiently in vortex rings in various domains.

In order to provide insight into how anisotropic nano-objects interact with living cell membranes, and possibly self-assemble, magnetic nanorods with an average size of around 100 nm × 1 µm are designed by assembling iron oxide nanocubes within a polymeric matrix under a magnetic field. The nano-bio interface at the cell membrane under the influence of a rotating magnetic field is then explored. A complex structuration of the nanorods intertwined with the membranes is observed. Unexpectedly, after a magnetic rotating stimulation, the resulting macrorods are able to rotate freely for multiple rotations, revealing the creation of a biomagnetic torsion pendulum., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The usage of micro or nanorods is steadily increasing in various applications from fundamental research to industry. Therefore their geometrical, mechanical and eventually magnetic properties need to be well determined. Here, using an optical microscope equipped with magnetic tweezers, we report an experimental procedure to obtain all those information on a single magnetic rod. In particular, we measure magnetic susceptibility χ by analyzing the deformation of a rod subjected to a uniform magnetic field. To do so, we refine a theoretical model which takes into account the variation of χ with the internal field. We prove experimentally that this model yields consistent measurements, at any value of the field strength and the incidence angle. From the combination of the different measurements, we also deduce the number of iron oxide nanoparticles which are embedded within the polymer matrix of the superparamagnetic rods under study.

Clusters of magnetic nanoparticles have received considerable interest in various research fields. Their capacity to generate heat under an alternating magnetic field has recently opened the way to applications such as cancer therapy by hyperthermia. This work is an attempt to investigate the collective effects of interacting dipoles embedded in magnetic nano-particles (MNP) to predict their thermal dissipation with a liquid. We first present a general approach, based on the tracking of the microscopic dipole fluctuations, to access to the dissipation spectra of any spatial distribution of MNPs. Without any other assumption that the linear response regime, it is shown that increasing the particle concentration (dipolar interactions) dramatically diminishes and blueshifts the dissipation processes. This effect originates in a predominance of the coupling energy over the Brownian torques, which create a long-range ordering that saturates the response of the system to an external field. Consequently, the particle density is of fundamental importance to the control of the absorption of electromagnetic energy and its subsequent dissipation in the form of heat.

We report results of a comprehensive study of the wetting properties of sessile drops of ferrofluid water solutions at various concentrations deposited on flat substrates and subjected to the action of permanent magnets of different sizes and strengths. The amplitude and the gradient of the magnetic field experienced by the ferrofluid are changed by varying the magnets and their distance to the surface. Magnetic forces up to 100 times the gravitational one and magnetic gradients up to 1 T/cm are achieved. A rich phenomenology is observed, ranging from flattened drops caused by the magnetic attraction to drops extended normally to the substrate because of the normal traction of the magnetic field. We find that the former effect can be conveniently described in terms of an effective Bond number that compares the effective drop attraction with the capillary force, whereas the drop's vertical elongation is effectively expressed by a dimensionless number S, which compares the pressure jump at the ferrofluid interface because of the magnetization with the capillary pressure.

In its simplest form the magnetoelastic buckling instability refers to the sudden bending transition of an elastic rod experiencing a uniform induction field applied at a normal angle with respect to its long axis. This fundamental physics phenomenon was initially documented in 1968, and, surprisingly, despite many refinements, a gap has always remained between the observations and the theoretical expectations. Here, we first renew the theory with a simple model based on the assumption that the magnetization follows the rod axis as soon as it bends. We demonstrate that the magnetoelastic buckling corresponds to a classical Landau second-order transition. Our model yields a solution for the critical field as well as the shape of the deformed rods which we compare with experiments on flexible ferromagnetic nickel rods at the centimeter scale. We also report this instability at the micrometer scale with specially designed rods made of nanoparticles. We characterized our samples by determining all of the relevant parameters (radius, length, Young modulus, magnetic susceptibility) and, using these values, we found that the theory fits extremely well the experimental results for both systems without any adjustable parameter. The superparamagnetic feature of the microrods also highlights the fact that ferromagnetic systems break the symmetry before the buckling. We propose a magnetic "stick-slip" model to explain this peculiar feature, which was visible in past reports but never detailed.

Cellular aggregates (spheroids) are widely used in biophysics and tissue engineering as model systems for biological tissues. In this Letter we propose novel methods for molding stem-cell spheroids, deforming them, and measuring their interfacial and elastic properties with a single method based on cell tagging with magnetic nanoparticles and application of a magnetic field gradient. Magnetic molding yields spheroids of unprecedented sizes (up to a few mm in diameter) and preserves tissue integrity. On subjecting these spheroids to magnetic flattening (over 150g), we observed a size-dependent elastocapillary transition with two modes of deformation: liquid-drop-like behavior for small spheroids, and elastic-sphere-like behavior for larger spheroids, followed by relaxation to a liquidlike drop.

A current challenge for tissue engineering while restoring the function of diseased or damaged tissue is to customize the tissue according to the target area. Scaffold-free approaches usually yield spheroid shapes with the risk of necrosis at the center due to poor nutrient and oxygen diffusion. Here, we used magnetic forces developed at the cellular scale by miniaturized magnets to create rod-shaped aggregates of stem cells that subsequently matured into a tissue-like structure. However, during the maturation process, the tissue-rods spontaneously bent and coiled into sphere-like structures, triggered by the increasing cell-cell adhesion within the initially non-homogeneous tissue. Optimisation of the intra-tissular magnetic forces successfully hindered the transition, in order to produce stable rod-shaped stem cells aggregates.

In recent decades, significant advances have been made in the description and modelling of tissue morphogenesis. By contrast, the initial steps leading to the formation of a tissue structure, through cell-cell adhesion, have so far been described only for small numbers of interacting cells. Here, through the use of remote magnetic forces, we succeeded at creating cell aggregates of half million cells, instantaneously and for several cell types, not only those known to form spheroids. This magnetic compaction gives access to the cell elasticity, found in the range of 800 Pa. The magnetic force can be removed at any time, allowing the cell mass to evolve spontaneously thereafter. The dynamics of contraction of these cell aggregates just after their formation (or, in contrast, their spreading for non-interacting monocyte cells) provides direct information on cell-cell interactions and allows retrieving the adhesion energy, in between 0.05 and 2 mJ m(-2), depending on the cell type tested, and in the case of cohesive aggregates. Thus, we show, by probing a large number of cell types, that cell aggregates behave like complex materials, undergoing a transition from a wet granular to contractile network, and that this transition is controlled by cell-cell interactions.

The intracellular microenvironment is essential for the efficiency of photo-induced therapies, as short-lived reactive oxygen species generated must diffuse through their intracellular surrounding medium to reach their cellular target. Here, by combining measurements of local cytoplasmic dissipation and active trafficking, we found that photosensitizers activation induced small changes in surrounding viscosity but a massive decrease in diffusion. These effects are the signature of a return to thermodynamic equilibrium of the system after photo-activation and correlated with depolymerization of the microtubule network, as shown in a reconstituted system. These mechanical measurements were performed with two intracellular photosensitizing chlorins having similar quantum yield of singlet oxygen production but different intracellular localizations (cytoplasmic for mTHPC, endosomal for TPCS2a). These two agents demonstrated different intracellular impact.

In the pursuit of optimized magnetic nanostructures for diagnostic and therapeutic applications, the role of nanoparticle architecture has been poorly investigated. In this study, we demonstrate that the internal collective organization of multi-core iron oxide nanoparticles can modulate their magnetic properties in such a way as to critically enhance their hyperthermic efficiency and their MRI T(1) and T(2) contrast effect. Multi-core nanoparticles composed of maghemite cores were synthesized through a polyol approach, and subsequent electrostatic colloidal sorting was used to fractionate the suspensions by size and hence magnetic properties. We obtained stable suspensions of citrate-stabilized nanostructures ranging from single-core 10 nm nanoparticles to multi-core magnetically cooperative 30 nm nanoparticles. Three-dimensional oriented attachment of primary cores results in enhanced magnetic susceptibility and decreased surface disorder compared to individual cores, while preserving a superparamagnetic-like behavior of the multi-core structures and potentiating thermal losses. Exchange coupling in the multi-core nanoparticles modifies the dynamics of the magnetic moment in such a way that both the longitudinal and transverse NMR relaxivities are also enhanced. Long-term MRI detection of tumor cells and their efficient destruction by magnetic hyperthermia can be achieved thanks to a facile and nontoxic cell uptake of these iron oxide nanostructures. This study proves for the first time that cooperative magnetic behavior within highly crystalline iron oxide superparamagnetic multi-core nanoparticles can improve simultaneously therapeutic and diagnosis effectiveness over existing nanostructures, while preserving biocompatibility.

Among the various locomotion strategies of the animal kingdom, the undulation locomotion is of particular interest for biomimetic applications. In this paper, we present an artificial swimmer set into motion by a new and non-trivial undulation mechanism, based on the twisting and buckling of its body. The swimmer consists of a long cylinder of ferrogel which is polarized transversely and in opposite directions at each extremity. When it is placed on a water film and submitted to a transverse oscillating magnetic field, the worm-like swimmer undulates and swims. Whereas symmetry breaking is due to the field gradient, the undulations of the worm result from a torsional buckling instability as the polarized ends tend to align with the applied magnetic field. The critical magnetic field above which buckling and subsequent swimming is observed may be predicted using elasticity equations including the effect of the magnetic torque. As the length of the worm is varied, several undulation modes are observed which are in good agreement with the bending modes of an elastic rod with free ends.

One of the first biointeractions of magnetic nanoparticles with living systems is characterized by nanoparticle-protein complex formation. The proteins dynamically encompass the particles in the protein corona. Here we propose a method based on nanomagnetism that allows a specific in situ monitoring of interactions between iron oxide nanoparticles and blood plasma. Tracking the nanoparticle orientation through their optical birefringence signal induced by an external magnetic field provides a quantitative real-time detection of protein corona at the surface of nanoparticles and assesses eventual onset of particle aggregation. Since some of the plasma proteins may cause particle aggregation, we use magnetic fractionation to separate the nanoparticle clusters (induced by "destabilizing proteins") from well-dispersed nanoparticles, which remain isolated due to a stabilizing corona involving other different types of proteins. Our study shows that the "biological identity" (obtained after the particles have interacted with proteins) and aggregation state (clustered versus isolated) of nanoparticles depend not only on their initial surface coating, but also on the concentration of plasma in the suspension. Low plasma concentrations (which are generally used in vitro) lead to different protein/nanoparticle complexes than pure plasma, which reflects the in vivo conditions. As a consequence, by mimicking in vivo conditions, we show that macrophages can perceive several different populations of nanoparticle/protein complexes (differing in physical state and in nature of associated proteins) and uptake them to a different extent. When extrapolated to what would happen in vivo, our results suggest a range of cell responses to a variety of nanoparticle/protein complexes which circulate in the body, thereby impacting their tissue distribution and their efficiency and safety for diagnostic and therapeutic use., (© 2012 American Chemical Society)

During the last decade, the development of nanomaterials to penetrate inside living cells has been the focus of a large number of studies, with applications for the biomedical field. However, the further dynamics of these nanomaterials inside the cells is dictated by the intracellular environment and in particular its mechanical properties. The mechanical characteristics of the cell interior can be probed with either active or passive microrheological approaches. However, active intracellular microrheology is still in its infancy, owing to the difficulty of inserting probes that can be manipulated by external forces. Here we review recent active microrheology studies using magnetic nanoprobes inserted into endosomes or phagosomes as useful approaches for measuring frequency-dependent viscoelasticity, for mapping the viscoelastic landscape, as well as for identifying the contribution of individual cytoskeleton components and the influence of cell motility. The results of such direct measurements challenge the validity of more typical passive approaches in which the spontaneous displacement of embedded nanoprobes is measured. Here we discuss that one must distinguish probes suitable for use in conditions of thermal equilibrium, whose movements reflect the mechanical environment from probes that interact actively with the cytoplasm and cytoskeleton, in a state of nonequilibrium for which fluctuation-dissipation theorem no longer holds. However, when data on these probes' viscoelastic microenvironment is available, such passive probe movements can yield useful information on the forces responsible for intracellular activity., (© 2012 American Physical Society)

We report the first observation of axisymmetric solitary waves on the surface of a cylindrical magnetic fluid layer surrounding a current-carrying metallic tube. According to the ratio between the magnetic and capillary forces, both elevation and depression solitary waves are observed with profiles in good agreement with theoretical predictions based on the magnetic analogue of the Korteweg-de Vries equation. We also report the first measurements of the velocity and the dispersion relation of axisymmetric linear waves propagating on the cylindrical ferrofluid layer that are found in good agreement with theoretical predictions.

By combining magnetic properties with nanosized biocompatible materials, superparamagnetic nanoparticles may serve as colloidal heating mediators for cancer therapy. This unique potential has attracted attention for designing new magnetic nanoparticles with high efficiency heating properties. Their heating power under high frequency magnetic field is governed by the mechanisms of magnetic energy dissipation for single-domain particles due both to internal Néel fluctuations of the particle magnetic moment and to the external Brownian fluctuations. These mechanisms are highly sensitive to the crystal size, the particle material, and the solvent properties. Here we explore the heating properties of maghemite particles with large particle sizes, in the range 15-50 nm, synthesized through a new procedure which includes a hydrothermal process. Particle shape and size distribution, hydrodynamic volume, and magnetic anisotropy are characterized, respectively, by transmission electron microscopy, dynamic magnetically induced birefringence, and ferromagnetic resonance. Together with our previous data on low diameter particles (Fortin J P et al 2007 J. Am. Chem. Soc 129 2628-35), this study provides the whole size dependence of heating efficiency in the range 5-50 nm and assesses the balance between Néel and Brownian contributions to thermal losses. In agreement with theoretical predictions, the heating efficiency shows a maximum for an optimal size of about 15 nm.

In severe nutriment conditions, the social amoeba Dictyostelium discoideum enters a particular life cycle where it forms multicellular patterns to achieve aggregation. Extensively observed from an initial dispersed state, its developmental program can usefully be studied from a confined population to implement theoretical developments regarding biological self-organization. The challenge is then to form a cell assembly of well-defined geometrical dimensions without hindering cell behavior. To achieve this goal, we imposed transient constraints by applying temporary external magnetic gradients to trap magnetically labeled cells. Deposits of various numbers of cells were geometrically characterized for different magnetic exposure conditions. We demonstrated that the cell deposit was organized as a three-dimensional (3D) structure by both stacking layers of cells and extending these layers in the substrate plane. This structure evolves during the aggregation phase, forming periodic aggregative centers along the linear initial pattern.

Upon drying, colloidal suspensions undergo a phase transformation from a "liquid" to a "gel" state. With further solvent evaporation, tensile stresses develop in the gel, which ultimately leads to fractures. These generally manifest themselves in regular cracking patterns which reflect the physical conditions of the drying process. Here we show experimentally and theoretically how, in the case of a drying droplet of magnetic colloid (ferrofluid), an externally applied magnetic field modifies the stress in the gel and therefore the crack patterns. We find that the analysis of the shape of the cracks allows one to estimate the value of the gel Young's modulus just before the crack nucleation.

Iron oxide colloidal nanomagnets generate heat when subjected to an alternating magnetic field. Their heating power, governed by the mechanisms of magnetic energy dissipation for single-domain particles (Brown and Néel relaxations), is highly sensitive to the crystal size, the material, and the solvent properties. This study was designed to distinguish between the contributions of Néel and Brownian mechanisms to heat generation. Anionic nanocrystals of maghemite and cobalt ferrite, differing by their magnetic anisotropy, were chemically synthesized and dispersed in an aqueous suspension by electrostatic stabilization. The particles were size-sorted by successive electrostatic phase separation steps. Parameters governing the efficiency of nanomagnets as heat mediators were varied independently; these comprised the particle size (from 5 to 16.5 nm), the solvent viscosity, magnetic anisotropy, and the magnetic field frequency and amplitude. The measured specific loss powers (SLPs) were in quantitative agreement with the results of a predictive model taking into account both Néel and Brown loss processes and the whole particle size distribution. By varying the carrier fluid viscosity, we found that Brownian friction within the carrier fluid was the main contributor to the heating power of cobalt ferrite particles. In contrast, Néel internal rotation of the magnetic moment accounted for most of the loss power of maghemite particles. Specific loss powers were varied by 3 orders of magnitude with increasing maghemite crystal size (from 4 to 1650 W/g at 700 kHz and 24.8 kA/m). This comprehensive parametric study provides the groundwork for the use of anionic colloidal nanocrystals to generate magnetically induced hyperthermia in various media, including complex systems and biological materials.

In micro-organisms, as well as in metazoan cells, cellular polarization and directed migration are finely regulated by external stimuli, including mechanical stresses. The mechanisms sustaining the transduction of such external stresses into intracellular biochemical signals remain mainly unknown. Using an external magnetic tip, we generated a magnetic field gradient that allows migration analysis of cells submitted to local low-intensity magnetic forces (50 pN). We applied our system to the amoeba Entamoeba histolytica. Indeed, motility and chemotaxis are key activities that allow this parasite to invade and destroy the human tissues during amoebiasis. The magnetic force was applied either inside the cytoplasm or externally at the rear pole of the amoeba. We observed that the application of an intracellular force did not affect cell polarization and migration, whereas the application of the force at the rear pole of the cell induced a persistent polarization and strongly directional motion, almost directly opposed to the magnetic force. This phenomenon was completely abolished when phosphatidylinositol 3-kinase activity was inhibited by wortmanin. This result demonstrated that the applied mechanical stimulus was transduced and amplified into an intracellular biochemical signal, a process that allows such low-intensity force to strongly modify the migration behavior of the cell.

Purpose: To establish the feasibility of magnetoliposome tumor targeting with an extracorporeal magnet., Materials and Methods: Animal experiments were performed in compliance with Institut National de la Santé Et de la Recherche Médicale animal protection guidelines and were approved by local government authorities. Magnetophoresis was used to measure the velocity of magnetoliposomes constituted of polyethylene glycol-lipids and anionic maghemite nanocrystals in a calibrated magnetic field in vitro. For in vivo studies, 38 male Swiss nude mice bearing a PC3 human prostate carcinoma tumor in each flank received an intravenous injection of magnetoliposomes (n = 27), saline (n = 9), or nonencapsulated superparamagnetic particles (n = 2) after a small magnet with a magnetic field of 0.3 T and a field gradient of 11 T/m was fixed to the skin above one tumor. The animals were examined at magnetic resonance (MR) imaging with eight different sequences, iron doses (13 mice), and magnet-application durations (12 mice). Their excised tumors were then stained with Perls Prussian blue and hematoxylin-eosin and were examined histologically. With use of the paired Student t test, signal intensity, tumor surface enhancement, and number of stained cells were compared between the control and magnet-exposed tumors to determine significant differences (P

It is recalled how the nonlinear interaction between a gas bubble and an external extra pressure can yield phase conjugation. Using the Glauber representation, we show that the effect of the latter is formally analogous to that of a pi pulse in nuclear magnetic resonance, so that the acoustic equivalent of spin echoes may be expected in a bubble cloud. An experimental attempt to observe phase conjugation is reported in the single-bubble case.

The dynamics of a two-dimensional N-bubble static cloud is investigated and shown to be well described by an N-degree of freedom harmonic oscillator model, at least at low enough frequencies. Eigenmodes and eigenfrequencies are calculated and compared with experimental results obtained with an assembly of bubbles caught up under a net in a water tank. Accordance is found to be excellent in the frequency range of validity of the model, the limits of which are discussed. An interpretation of the low-frequency branch of Foldy's dispersion relation in bubbly liquids is suggested in terms of "bubble waves" in a quasi-incompressible medium.

The mechanical behavior of the human parasite Entamoeba histolytica plays a major role in the invasive process of host tissues and vessels. In this study, we set up an intracellular rheological technique derived from magnetic tweezers to measure the viscoelastic properties within living amoebae. The experimental setup combines two magnetic fields at 90 degrees from each other and is adapted to an inverted microscope, which allows monitoring of the rotation of pairs of magnetic phagosomes. We observe either the response of the phagosome pair to an instantaneous 45 degrees rotation of the magnetic field or the response to a permanent uniform rotation of the field at a given frequency. By the first method, we concluded that the phagosome pairs experience a soft viscoelastic medium, represented by the same mechanical model previously described for the cytoplasm of Dictyostelium discoideum [Feneberg et al. in Eur Biophys J 30(4):284-294 2001]. By the second method, the permanent rotation of a pair allowed us to apply a constant shear rate and to calculate the apparent viscosity of the cytoplasm. As found for entangled polymers, the viscosity decreases with the shear rate applied (shear-thinning behavior) and exhibits a power-law-type thinning, with a corresponding exponent of 0.65. Treatment of amoeba with drugs that affect the actin polymer content demonstrated that the shear-thinning behavior of the cytoplasm depends on the presence of an intact actin cytoskeleton. These data present a physiologic relevance for Entamoeba histolytica virulence. The shear-thinning behavior could facilitate cytoplasm streamings during cell movement and cell deformation, under important shear experienced by the amoeba during the invasion of human tissues. In this study, we also investigated the role of the actin-based motor myosin II and concluded that myosin II stiffens the F-actin gel in living parasites likely by its cross-linking activity.

The feasibility of in vivo cellular imaging using a 1.5 T clinical magnet was studied in the mouse. Hybridoma cells were labeled with anionic gamma-Fe2O3 superparamagnetic iron oxide nanoparticles. These were internalized by the endocytose pathway. Both electron spin resonance and magnetophoresis as a measure of the labeled cells migration velocity under a magnetic field were used to quantify particle uptake. A fast (< 2 hr) and substantial (up to 5 pg of iron per cell) internalization of nanoparticles by hybridomas was found, with good agreement between the two methods used. Hybridomas labeled with 2.5 pg iron per cell were injected intraperitoneally to male Swiss nude mice. A decrease in the spleen signal, suggesting a "homing" of labeled hybridomas to this organ, was found 24 hr later by MRI performed at 1.5 T. Furthermore, in labeled cells recovered from the spleen by ex vivo magnetic sorting, a mean of 0.5 pg iron per cell was found, i.e., a value five times lower than that of the injected hybridomas. This finding is consistent with in vivo proliferation of these cells. In addition, the amount of labeled hybridomas present in the spleen was found to correlate with MRI signal intensity., (Copyright 2004 Wiley-Liss, Inc.)

The human parasite Entamoeba histolytica is an ancient protozoan that expresses only one unconventional myosin, which has homology with myosin IB from other amoebae. Myosin IB is involved in phagocytosis of human cells by E. histolytica. In this work, we developed a microrheological technique, analysing magnetic phagosomes, which allowed us to probe the density of the F-actin network in living cells. Using this technique, we showed that overexpression of myosin IB led to an increase in cytoplasm viscosity, which correlated with a delay in initiating human cell phagocytosis. To investigate which myosin IB domains sustain cell viscosity changes, we overexpressed truncated forms of the protein. Our results demonstrate that both actin-binding sites that are present in the heavy chain but not the SH3 domain are required to modulate the density of the actin network. These data suggested that, as well as the motor activity, myosin IB in E. histolytica plays a structural role on the actin network owing to its ability to cross-link filaments. The gelation state of cell cytoplasm and the dynamics of cortical F-actin during phagocytosis seem to be modulated by the myosin IB structuring cytoskeleton activity.

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.

The previously developed technique of magnetic rotational microrheology [Phys. Rev. E 67, 011504 (2003)] is proposed to investigate the rheological properties of the cell interior. An endogeneous magnetic probe is obtained inside living cells by labeling intracellular compartments with magnetic nanoparticles, following the endocytosis mechanism, the most general pathway used by eucaryotic cells to internalize substances from an extracellular medium. Primarily adsorbed on the plasma membrane, the magnetic nanoparticles are first internalized within submicronic membrane vesicles (100 nm diameter) to finally concentrate inside endocytotic intracellular compartments (0.6 microm diameter). These magnetic endosomes attract each other and form chains within the living cell when submitted to an external magnetic field. Here we demonstrate that these chains of magnetic endosomes are valuable tools to probe the intracellular dynamics at very local scales. The viscoelasticity of the chain microenvironment is quantified in terms of a viscosity eta and a relaxation time tau by analyzing the rotational dynamics of each tested chain in response to a rotation of the external magnetic field. The viscosity eta governs the long time flow of the medium surrounding the chains and the relaxation time tau reflects the proportion of solidlike versus liquidlike behavior (tau=eta/G, where G is the high-frequency shear modulus). Measurements in HeLa cells show that the cell interior is a highly heterogeneous structure, with regions where chains are embedded inside a dense viscoelastic matrix and other domains where chains are surrounded by a less rigid viscoelastic material. When one compound of the cell cytoskeleton is disrupted (microfilaments or microtubules), the intracellular viscoelasticity becomes less heterogeneous and more fluidlike, in the sense of both a lower viscosity and a lower relaxation time.

Anionic iron oxide nanoparticles are efficiently internalized into macrophages where they concentrate within micrometric endosomes, conferring on them a high magnetic susceptibility. The uptake of anionic maghemite nanoparticles by macrophages was quantified by an electron spin resonance (ESR) experiment. MR spin-echo sequences were performed with various TEs and TRs. The contrast enhancement was compared between two types of agarose phantoms with the same equivalent ferrite concentrations but containing either dispersed isolated nanoparticles or magnetically labeled macrophages. It is shown that the intracellular confinement of maghemite nanoparticles within micrometric endosomes results in a significant decrease of the longitudinal relaxivity and a moderate decrease of the transverse relaxivity compared to the relaxivities of the dispersed isolated nanoparticles. As a consequence, the signature of endosomal magnetic labeling consists of a negative contrast on T(1)-weighted images in the whole ferrite concentration range, whereas the presence of extracellular isolated nanoparticles can result in a positive enhancement., (Copyright 2003 Wiley-Liss, Inc.)

A new class of superparamagnetic nanoparticles bearing negative surface charges is presented. These anionic nanoparticles show a high affinity for the cell membrane and, as a consequence, are captured by cells with an efficiency three orders of magnitude higher than the widely used dextran-coated iron oxide nanoparticles. The surface coating of anionic particle with albumin strongly reduces the non specific interactions with the plasma membrane as well as the overall cell uptake and at the same time restores the ability to induce specific interactions with targeted cells by the coadsorption on the particle surface of a specific ligand. Kinetics of cellular particle uptake for different cell lines are quantitated using two new complementary assays (Magnetophoresis and Electron Spin Resonance).

An experimental method based on the rotational dynamics of a magnetic probe is reported to measure the local viscoelasticity of soft materials on microscopic scales. The technique is based on the alignment of dipolar chains of submicrometer magnetic particles in the direction of an applied magnetic field. On one hand, light scattering is used to detect the chains' oscillations over a 0.001-100 Hz frequency range when submitted to an oscillating magnetic field and leads to global microrheological measurements. On the other hand, the chains' rotation toward a permanent magnetic field is observed with a microscope, allowing a local determination of viscoelastic properties on the scale of the chains of particles. We demonstrate the accuracy of both assays with a micellar Maxwellian solution and validate theoretical predictions.

We present an experimental method allowing a direct measurement of the local rheological behavior of complex fluids. A magnetic probe is inserted into the bulk of the fluid and submitted to a controlled magnetic force or torque, which induces a mechanical perturbation of the fluid. The geometry of the perturbation can be varied using two kinds of probes: a magnetic bead submitted to a homogeneous magnetic force in one direction, and a magnetic needle that can turn inside the material under the effect of an applied magnetic torque. Two complex viscoelastic fluids are investigated. First, a surfactant solution, which has a linear mechanical behavior in the range of the applied stresses, is used to test and validate the experimental methodology. We then use the local probes to investigate a Laponite colloidal suspension, which exhibits nonlinear behavior such as thixotropy, shear thinning, and aging. In this latter fluid, we find an exponential growth of the rheological relaxation time versus the system age, a power-law dependence of the fluid viscosity on the applied stress, and a dynamical yield stress which saturates with the fluid aging time.

Dynamic birefringence in a ferrofluid subjected to crossed bias (constant) and probing (pulse or ac) fields is considered, assuming that the nanoparticles have finite magnetic anisotropy. This is done on the basis of the general Fokker-Planck equation that takes into account both internal magnetic and external mechanical degrees of freedom of the particle. We describe the orientation dynamics in terms of the integral relaxation time of the macroscopic orientation order parameter. To account for an arbitrary relation between the bias (external) and anisotropy (internal) fields, an interpolation expression for the integral relaxation time is proposed and justified. A developed description is used to interpret the measurements of birefringence relaxation in magnetic fluids with nanoparticles of high (cobalt ferrite) and low (maghemite) anisotropy. The proposed theory appears to be in full qualitative agreement with all the experimental data available.

We develop in this paper two methods, based on different physical concepts, to quantify the uptake of magnetic nanoparticles in biological cells. The first one, magnetophoresis, is based on the measurement of the velocity of magnetically labeled cells submitted to a magnetic field gradient. The second one quantitates the particles' electronic spin using an electron paramagnetic resonance experiment. We show a quantitative agreement between both methods for macrophagic cells. The uptake kinetics and uptake capacity are discussed for macrophagic cells and other cell lines.

We propose here a method to modify the membrane tension of phospholipid tubes with an applied magnetic field. The tubes are connected to giant liposomes capping the tubes at both ends. Tubes and liposomes are all filled with a magnetic fluid. The tension of the tube membrane is tuned by the deformation of the ending liposomes under the applied field. We modelize the magnetoliposome deformation and we are then able to describe the tube evolution. At low magnetic fields, the tube remains at equilibrium with a cylindrical shape and a uniform radius. It responds to an increase of membrane tension by a diameter reduction. Above a magnetic-field threshold, the cylindrical shape becomes unstable with respect to a pearling deformation. The tube shape then selected by the system is an unduloid, with a constant mean curvature equal to C 0, the spontaneous curvature of the membrane.

Small-angle neutron scattering is used to measure the two-dimensional diffraction pattern of a monophasic magnetic colloid, under an applied magnetic field. This dipolar system presents in zero field a fluidlike structure. It is well characterized by an interaction parameter K(0)(T) proportional to the second virial coefficient, which is here positive, expressing a repulsion of characteristic length kappa-10. Under the field a strong anisotropy is observed at the lowest q vectors. The length kappa-10 remains isotropic, but the interaction parameter K(T) becomes anisotropic due to the long-range dipolar interaction. However, the system remains stable, the interaction being repulsive in all directions. Thus we do not observe any chaining of the nanoparticles under magnetic field. On the contrary, the revealed structure of our anisotropic colloid is a lowering of the concentration fluctuations along the field while the fluidlike structure, observed without field, is roughly preserved perpendicularly to the field. It expresses a strong anisotropy of the Brownian motion of the nanoparticles in the solution under applied field.

We have investigated the relaxation of the magnetically induced birefringence in a suspension of magnetic nanoparticles in order to detect the binding reaction of polyclonal antibodies on the particle surface. The birefringence relaxation is driven by the rotational diffusion of the complex formed by the magnetic nanoparticles bound to the antibody and thus is directly related to the hydrodynamic size of this complex. Birefringence relaxations are well described by stretched exponential laws revealing a polydisperse distribution of hydrodynamic diameters. Comparing the size distribution of samples with different initial ratios of immunoglobuline added per magnetic nanoparticles, we evidence the graft of an antibody on particle and eventually the onset of particles aggregation. Measurements on samples separated in size by gel filtration demonstrate the robustness of our experiment for the determination of size distribution and its modification due to the adsorption of a macromolecule. The immunoglobuline binding assay is performed comparatively for ionic magnetic nanoparticles with different coatings.

This paper shows how forced Rayleigh scattering can be used as an experimental tool for studying thermodiffusion (Soret effect). The systems investigated are magnetic colloids of different types. A framework including thermodiffusion and dielectrophoresis is described in which the evolutions of temperature and of colloid concentration are clearly distinguished. The framework is then shown to account for experiments on steady-state concentration gratings coupled with transient temperature ones, and the parameters are determined therefrom. Dielectrophoretic forces are found to be negligible. Studying different types of magnetic colloids with various dilution rates shows that the sign of the Soret effect is controlled by the nature of the particle coating made up of electrostatic charges or of surfactant, and that its mechanism is located at the nanoparticle core-solvent interface.

We present experiments showing the Rayleigh-Taylor instability at the interface between a dense magnetic liquid and an immiscible less dense liquid. The liquids are confined in a Hele-Shaw cell and a magnetic field is applied perpendicular to the cell. We measure the wavelength and the growth rate at the onset of the instability as a function of the external magnetic field. The wavelength decreases as the field increases. The amplitude of the interface deformation grows exponentially with time in the early stage, and the growth rate is an increasing function of the field. These results are compared to theoretical predictions given in the framework of linear stability analysis.

We explore how a magnetic field breaks the symmetry of an initially spherical giant liposome filled with a magnetic colloid. The condition of rotational symmetry along the field axis leads either to a prolate or to an oblate ellipsoid. We demonstrate that an electrostatic interaction between the nanoparticles and the membrane triggers the shape transition.

The use of cell-targeted ferrofluid in the characterization of modifications of cell membranes is reviewed. Maghemite ferrofluid was synthesized by the Massart method, complexed with dimercaptosuccinic acid (FF). Cell targeting by FF was developed by coupling FF to various biological effectors such as antibodies, lectins, etc, which enabled magnetic cell sorting. Modifications in erythrocyte membranes were studied using FF bound to recombinant human annexin V (AnxFF) which is very sensitive, compared to other Anx-based reagents, in the early detection of phosphatidylserine (PS) exposition on the outer leaflet of the plasma membrane. Thus PS exposition on mouse RBC was detected already after a 24-h storage at 4 degrees C and, transiently, 24 h after their infection by Plasmodium parasites, at which time the parasites are still confined to the liver, thus leading to the recruitment of young RBC and the accumulation of a species, intermediate between reticulocytes and erythrocytes, and the actual RBC target of plasmodial invasion. AnxFF revealed PS exposition on RBC from sickle cell anemia patients, following various inflammations and already after 20 days of human blood storage under blood bank conditions. Such a sensitive detection should be similar to that of macrophages which recognize exposed PS on cells and bring about the latter's elimination from the circulation. AnxFF binding determination was combined with that of cell electrophoretic mobility, glycerol resistance and filterability to characterize RBC membrane modifications in Alzheimer's disease patients which suggested a continuous damage and regeneration in RBC of these patients. A logistic analysis suggested that several three-parameter combinations could permit diagnosis of Alzheimer's disease with up to 95% accuracy. THP1 cells and macrophages, derived themselves by incubation with retinoic acid, were bound to FF and placed in a radio frequency alternating magnetic field. Magnetocytolysis was associated with FF attachment to the cells without damage to non-bound cells and without heating of the surrounding solution.