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The nucleus of eukaryotic cells is constantly subjected to different kinds of mechanical stimuli, which can impact the organization of chromatin and, subsequently, the expression of genetic information. Experiments from different groups showed that nuclear deformation can lead to transient or permanent condensation or decondensation of chromatin and the mechanical activation of genes, thus altering the transcription of proteins. Changes in chromatin organization, in turn, change the mechanical properties of the nucleus, possibly leading to an auxetic behavior. Here, we model the mechanics of the nucleus as a chemically active polymer gel in which the chromatin can exist in two states: a self-attractive state representing the heterochromatin and a repulsive state representing euchromatin. The model predicts reversible or irreversible changes in chromatin condensation levels upon external deformations of the nucleus. We find an auxetic response for a broad range of parameters under small and large deformations. These results agree with experimental observations and highlight the key role of chromatin organization in the mechanical response of the nucleus.
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We report the emergence of large zigzag bands in a population of reversibly actuated magnetic rotors that behave as active shakers, namely squirmers that shake the fluid around them without moving. The shakers collectively organize into dynamic structures displaying self-similar growth and generate topological defects in the form of cusps that connect vortices of rolling particles with alternating chirality. By combining experimental analysis with particle-based simulation, we show that the special flow field created by the shakers is the only ingredient needed to reproduce the observed spatiotemporal pattern. We unveil a self-organization scenario in a collection of driven particles in a viscoelastic medium emerging from the reduced particle degrees of freedom, as here the frozen orientational motion of the shakers.
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Similar to cells, bacteria, and other micro-organisms, synthetic chemically active colloids can harness the energy from their environment through a surface chemical reaction and use the energy to self-propel in fluidic environments. In this paper, we study the chemo-mechanical coupling that leads to the self-propulsion of chemically active colloids. The coupling between chemical reactions and momentum transport is a consequence of Onsager reciprocal relations. They state that the velocity and the surface reaction rate are related to mechanical and chemical affinities through a symmetric matrix. A consequence of Onsager reciprocal relations is that if a chemical reaction drives the motion of the colloid, then an external force generates a reaction rate. Here, we investigate Onsager reciprocal relations for a spherical active colloid that catalyzes a reversible surface chemical reaction between two species. We solve the relevant transport equations using a perturbation expansion and numerical simulations to demonstrate the validity of reciprocal relations around the equilibrium. Our results are consistent with previous studies and highlight the key role of solute advection in preserving the symmetry of the Onsager matrix. Finally, we show that Onsager reciprocal relations break down around a nonequilibrium steady state, which has implications for the thermal fluctuations of the active colloids used in experiments.
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Coloides , Coloides/química , Movimiento (Física) , SolucionesRESUMEN
Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors.
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Células Artificiales/química , Enzimas/química , Simulación por Computador , Fluidez de la Membrana , Modelos Biológicos , Movimiento (Física) , Procesos EstocásticosRESUMEN
Polar active particles constitute a wide class of active matter that is able to propel along a preferential direction, given by their polar axis. Here, we demonstrate a generic active mechanism that leads to their spontaneous chiralization through a symmetry-breaking instability. We find that the transition of an active particle from a polar to a chiral symmetry is characterized by the emergence of active rotation and of circular trajectories. The instability is driven by the advection of a solute that interacts differently with the two portions of the particle surface and it occurs through a supercritical pitchfork bifurcation.
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Bioinspired hybrid soft robots that combine living and synthetic components are an emerging field in the development of advanced actuators and other robotic platforms (i.e., swimmers, crawlers, and walkers). The integration of biological components offers unique characteristics that artificial materials cannot precisely replicate, such as adaptability and response to external stimuli. Here, we present a skeletal muscle-based swimming biobot with a three-dimensional (3D)-printed serpentine spring skeleton that provides mechanical integrity and self-stimulation during the cell maturation process. The restoring force inherent to the spring system allows a dynamic skeleton compliance upon spontaneous muscle contraction, leading to a cyclic mechanical stimulation process that improves the muscle force output without external stimuli. Optimization of the 3D-printed skeletons is carried out by studying the geometrical stiffnesses of different designs via finite element analysis. Upon electrical actuation of the muscle tissue, two types of motion mechanisms are experimentally observed: directional swimming when the biobot is at the liquid-air interface and coasting motion when it is near the bottom surface. The integrated compliant skeleton provides both the mechanical self-stimulation and the required asymmetry for directional motion, displaying its maximum velocity at 5 hertz (800 micrometers per second, 3 body lengths per second). This skeletal muscle-based biohybrid swimmer attains speeds comparable with those of cardiac-based biohybrid robots and outperforms other muscle-based swimmers. The integration of serpentine-like structures in hybrid robotic systems allows self-stimulation processes that could lead to higher force outputs in current and future biomimetic robotic platforms.
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Biomimética/instrumentación , Robótica/instrumentación , Animales , Órganos Artificiales , Materiales Biomiméticos , Línea Celular , Diseño de Equipo , Análisis de Elementos Finitos , Fenómenos Mecánicos , Ratones , Movimiento (Física) , Músculo Esquelético/citología , Músculo Esquelético/fisiología , Impresión Tridimensional , Materiales Inteligentes , Natación , Andamios del TejidoRESUMEN
We study the self-propulsion of a charged colloidal particle that releases ionic species using theory and experiments. We relax the assumptions of thin Debye length and weak nonequilibrium effects assumed in classical phoretic models. This leads to a number of unexpected features that cannot be rationalized considering the classic phoretic framework: an active particle can reverse the direction of motion by increasing the rate of ion release and can propel even with zero surface charge. Our theory predicts that there are optimal conditions for self-propulsion and a novel regime in which the velocity is insensitive to the background electrolyte concentration. The theoretical results quantitatively capture the salt-dependent velocity measured in our experiments using active colloids that propel by decomposing urea via a surface enzymatic reaction.
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The combined use of ultrasound radiation and microfluidics is a promising tool for aiding the development of lab-on-a-chip devices. In this study, we show that the rotation of linear aggregates of micro-particles can be achieved under the action of acoustic field pressure. This novel manipulation is investigated by tracking polystyrene beads of different sizes through the 3D imaging features of digital holography (DH). From our analysis it is understood that the positioning of the micro-particles and their aggregations are associated with the effect of bulk acoustic radiation forces. The observed rotation is instead found to be compatible with the presence of acoustic streaming patterns as evidenced by our modelling and the resulting numerical simulation. Furthermore, the rotation frequency is shown to depend on the input voltage applied on the acoustic device. Finally, we demonstrate that we can take full advantage of such rotation by combining it with quantitative phase imaging of DH for a significant lab-on-a-chip biomedical application. In fact, we demonstrate that it is possible to put in rotation a linear aggregate of erythrocytes and rely on holographic imaging to achieve a full phase-contrast tomography of the aforementioned aggregate.
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Acústica , Eritrocitos/citología , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas , Tomografía , Acústica/instrumentación , Humanos , Técnicas Analíticas Microfluídicas/instrumentación , Presión , Rotación , Tomografía/instrumentaciónRESUMEN
Biomedical microbubbles stabilized by a coating of magnetic or drug-containing nanoparticles show great potential for theranostics applications. Nanoparticle-coated microbubbles can be made to be stable, to be echogenic, and to release the cargo of drug-containing nanoparticles with an ultrasound trigger. This Article reviews the design principles of nanoparticle-coated microbubbles for ultrasound imaging and drug delivery, with a particular focus on the physical chemistry of nanoparticle-coated interfaces; the formation, stability, and dynamics of nanoparticle-coated bubbles; and the conditions for controlled nanoparticle release in ultrasound. The emerging understanding of the modes of nanoparticle expulsion and of the transport of expelled material by microbubble-induced flow is paving the way toward more efficient nanoparticle-mediated drug delivery. This Article highlights the knowledge gap that still remains to be addressed before we can control these phenomena.
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Medios de Contraste/química , Portadores de Fármacos/química , Microburbujas , Nanopartículas/química , Ultrasonografía/métodosRESUMEN
High-rate deformation of soft matter is an emerging area central to our understanding of far-from-equilibrium phenomena during shock, fracture, and phase change. Monolayers of colloidal particles are a convenient two-dimensional model system to visualise emergent behaviours in soft matter, but previous studies have been limited to slow deformations. Here we probe and visualise the evolution of a monolayer of colloids confined at a bubble surface during high-rate deformation driven by ultrasound. We observe the emergence of a transient network of strings, and use discrete particle simulations to show that it is caused by a delicate interplay of dynamic capillarity and hydrodynamic interactions between particles oscillating at high frequency. Remarkably for a colloidal system, we find evidence of inertial effects, caused by accelerations approaching 10,000g. These results also suggest that extreme deformation of soft matter offers new opportunities for pattern formation and dynamic self-assembly.
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Monolayers of ligand-grafted nanoparticles at fluid interfaces exhibit a complex response to deformation due to an interplay of particle rearrangements within the monolayer, and molecular rearrangements of the ligand brush on the surface of the particles. We use grazing-incidence small-angle X-ray scattering (GISAXS) combined with pendant drop tensiometry to probe in situ the dynamic organization of ligand-grafted nanoparticles upon adsorption at a fluid-fluid interface, and during monolayer compression. Through the simultaneous measurements of interparticle distance, obtained from GISAXS, and of surface pressure, obtained from pendant drop tensiometry, we link the interfacial stress to the monolayer microstructure. The results indicate that, during adsorption, the nanoparticles form rafts that grow while the interparticle distance remains constant. For small-amplitude, slow compression of the monolayer, the evolution of the interparticle distance bears a signature of ligand rearrangements leading to a local decrease in thickness of the ligand brush. For large-amplitude compression, the surface pressure is found to be strongly dependent on the rate of compression. Two-dimensional Brownian dynamics simulations show that the rate-dependent features are not due to jamming of the monolayer, and suggest that they may be due to out-of-plane reorganization of the particles (for instance expulsion or buckling). The corresponding GISAXS patterns are also consistent with out-of-plane reorganization of the nanoparticles.
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Ultrasound-driven microbubble dynamics are central to biomedical applications, from diagnostic imaging to drug delivery and therapy. In therapeutic applications, the bubbles are typically embedded in tissue, and their dynamics are strongly affected by the viscoelastic properties of the soft solid medium. While the behaviour of bubbles in Newtonian fluids is well characterised, a fundamental understanding of the effect on ultrasound-driven bubble dynamics of a soft viscoelastic medium is still being developed. We characterised the resonant behaviour in ultrasound of isolated microbubbles embedded in agarose gels, commonly used as tissue-mimicking phantoms. Gels with different viscoelastic properties were obtained by tuning agarose concentration, and were characterised by standard rheological tests. Isolated bubbles (100-200 µm) were excited by ultrasound (10-50 kHz) at small pressure amplitudes (<1 kPa), to ensure that the deformation of the material and the bubble dynamics remained in the linear regime. The radial dynamics of the bubbles were recorded by high-speed video microscopy. Resonance curves were measured experimentally and fitted to a model combining the Rayleigh-Plesset equation governing bubble dynamics, with the Kelvin-Voigt model for the viscoelastic medium. The resonance frequency of the bubbles was found to increase with increasing shear modulus of the medium, with implications for optimisation of imaging and therapeutic ultrasound protocols. In addition, the viscoelastic properties inferred from ultrasound-driven bubble dynamics differ significantly from those measured at low frequency with the rheometer. Hence, rheological characterisation of biomaterials for medical ultrasound applications requires particular attention to the strain rate applied.
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In this paper, we investigate the dynamics of a model spherical microorganism, called squirmer, suspended in a viscoelastic fluid undergoing unconfined shear flow. The effect of the interplay of shear flow, fluid viscoelasticity, and self-propulsion on the orientational dynamics is addressed. In the limit of weak viscoelasticity, quantified by the Deborah number, an analytical expression for the squirmer angular velocity is derived by means of the generalized reciprocity theorem. Direct finite element simulations are carried out to study the squirmer dynamics at larger Deborah numbers. Our results show that the orientational dynamics of active microorganisms in a sheared viscoelastic fluid greatly differs from that observed in Newtonian suspensions. Fluid viscoelasticity leads to a drift of the particle orientation vector towards the vorticity axis or the flow-gradient plane depending on the Deborah number, the relative weight between the self-propulsion velocity and the flow characteristic velocity, and the type of swimming. Generally, pullers and pushers show an opposite equilibrium orientation. The results reported in the present paper could be helpful in designing devices where separation of microorganisms, based on their self-propulsion mechanism, is obtained.