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Cells migrate by adapting their leading-edge behaviors to heterogeneous extracellular microenvironments (ECMs) during cancer invasions and immune responses. Yet it remains poorly understood how such complicated dynamic behaviors emerge from millisecond-scale assembling activities of protein molecules, which are hard to probe experimentally. To address this gap, we establish a spatiotemporal "resistance-adaptive propulsion" theory based on the interactions between Arp2/3 complexes and polymerizing actin filaments and a multiscale dynamic modeling system spanning from molecular proteins to the cell. We quantitatively find that cells can accurately self-adapt propulsive forces to overcome heterogeneous ECMs via a resistance-triggered positive feedback mechanism, dominated by polymerization-induced actin filament bending and the bending-regulated actin-Arp2/3 binding. However, for high resistance regions, resistance triggers a negative feedback, hindering branched filament assembly, which adapts cellular morphologies to circumnavigate the obstacles. Strikingly, the synergy of the two opposite feedbacks not only empowers the cell with both powerful and flexible migratory capabilities to deal with complex ECMs but also enables efficient utilization of intracellular proteins by the cell. In addition, we identify that the nature of cell migration velocity depending on ECM history stems from the inherent temporal hysteresis of cytoskeleton remodeling. We also show that directional cell migration is dictated by the competition between the local stiffness of ECMs and the local polymerizing rate of actin network caused by chemotactic cues. Our results reveal that it is the polymerization force-regulated actin filament-Arp2/3 complex binding interaction that dominates self-adaptive cell migrations in complex ECMs, and we provide a predictive theory and a spatiotemporal multiscale modeling system at the protein level.
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Citoesqueleto de Actina , Actinas , Polimerização , Movimento Celular , Citoesqueleto , Complexo 2-3 de Proteínas Relacionadas à ActinaRESUMO
Morphogenesis of active shells such as cells is a fundamental chemomechanical process that often exhibits three-dimensional (3D) large deformations and chemical pattern dynamics simultaneously. Here, we establish a chemomechanical active shell theory accounting for mechanical feedback and biochemical regulation to investigate the symmetry-breaking and 3D chiral morphodynamics emerging in the cell cortex. The active bending and stretching of the elastic shells are regulated by biochemical signals like actomyosin and RhoA, which, in turn, exert mechanical feedback on the biochemical events via deformation-dependent diffusion and inhibition. We show that active deformations can trigger chemomechanical bifurcations, yielding pulse spiral waves and global oscillations, which, with increasing mechanical feedback, give way to traveling or standing waves subsequently. Mechanical feedback is also found to contribute to stabilizing the polarity of emerging patterns, thus ensuring robust morphogenesis. Our results reproduce and unravel the experimentally observed solitary and multiple spiral patterns, which initiate asymmetric cleavage in Xenopus and starfish embryogenesis. This study underscores the crucial roles of mechanical feedback in cell development and also suggests a chemomechanical framework allowing for 3D large deformation and chemical signaling to explore complex morphogenesis in living shell-like structures.
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Fenômenos Químicos , Citoesqueleto de Actina , Actomiosina , Diferenciação Celular , Físico-Química , MorfogêneseRESUMO
Human brain experiences vibration of certain magnitude and frequency during various physical activities such as vehicle transportation and machine operation, which may cause traumatic brain injury or other brain diseases. However, the mechanisms of brain pathogenesis due to vibration are not fully elucidated due to the lack of techniques to study brain functions while applying vibration to the brain at a specific magnitude and frequency. Here, this study reported a custom-built head-worn electromagnetic actuator that applied vibration to the brain in vivo at an accurate frequency inside a magnetic resonance imaging scanner while cerebral blood flow (CBF) was acquired. Using this technique, CBF values from 45 healthy volunteers were quantitatively measured immediately following vibration at 20, 30, 40 Hz, respectively. Results showed increasingly reduced CBF with increasing frequency at multiple regions of the brain, while the size of the regions expanded. Importantly, the vibration-induced CBF reduction regions largely fell inside the brain's default mode network (DMN), with about 58 or 46% overlap at 30 or 40 Hz, respectively. These findings demonstrate that vibration as a mechanical stimulus can change strain conditions, which may induce CBF reduction in the brain with regional differences in a frequency-dependent manner. Furthermore, the overlap between vibration-induced CBF reduction regions and DMN suggested a potential relationship between external mechanical stimuli and cognitive functions.
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Encéfalo , Vibração , Humanos , Imageamento por Ressonância Magnética , Cognição , Circulação Cerebrovascular/fisiologiaRESUMO
Ventral bending of the embryonic tail within the chorion is an evolutionarily conserved morphogenetic event in both invertebrates and vertebrates. However, the complexity of the anatomical structure of vertebrate embryos makes it difficult to experimentally identify the mechanisms underlying embryonic folding. This study investigated the mechanisms underlying embryonic tail bending in chordates. To further understand the mechanical role of each tissue, we also developed a physical model with experimentally measured parameters to simulate embryonic tail bending. Actomyosin asymmetrically accumulated at the ventral side of the notochord, and cell proliferation of the dorsal tail epidermis was faster than that in the ventral counterpart during embryonic tail bending. Genetic disruption of actomyosin activity and inhibition of cell proliferation dorsally caused abnormal tail bending, indicating that both asymmetrical actomyosin contractility in the notochord and the discrepancy of epidermis cell proliferation are required for tail bending. In addition, asymmetrical notochord contractility was sufficient to drive embryonic tail bending, whereas differential epidermis proliferation was a passive response to mechanical forces. These findings showed that asymmetrical notochord contractility coordinates with differential epidermis proliferation mechanisms to drive embryonic tail bending.This article has an associated 'The people behind the papers' interview.
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Actomiosina/genética , Morfogênese/genética , Cauda/crescimento & desenvolvimento , Actomiosina/metabolismo , Animais , Proliferação de Células/genética , Ciona/embriologia , Ciona/genética , Ciona/crescimento & desenvolvimento , Células Epiteliais/metabolismo , Contração Muscular/fisiologia , Notocorda/embriologia , Notocorda/crescimento & desenvolvimento , Cauda/embriologiaRESUMO
Atomic reconstruction has been widely observed in two-dimensional van der Waals structures with small twist angles1-7. This unusual behaviour leads to many novel phenomena, including strong electronic correlation, spontaneous ferromagnetism and topologically protected states1,5,8-14. Nevertheless, atomic reconstruction typically occurs spontaneously, exhibiting only one single stable state. Using conductive atomic force microscopy, here we show that, for small-angle twisted monolayer-multilayer graphene, there exist two metastable reconstruction states with distinct stacking orders and strain soliton structures. More importantly, we demonstrate that these two reconstruction states can be reversibly switched, and the switching can propagate spontaneously in an unusual domino-like fashion. Assisted by lattice-resolved conductive atomic force microscopy imaging and atomistic simulations, the detailed structure of the strain soliton networks has been identified and the associated propagation mechanism is attributed to the strong mechanical coupling among solitons. The fine structure of the bistable states is critical for understanding the unique properties of van der Waals structures with tiny twists, and the switching mechanism offers a viable means for manipulating their stacking states.
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Grafite , Eletrônica , Grafite/químicaRESUMO
The growth of biological tissues, which is regulated by a variety of factors, can induce stresses that may, in turn, destabilize the tissues into diverse patterns. In most previous studies, however, tissue growth was usually assumed as a prescribed parameter independent of stresses, limiting our understanding of the mechanobiological morphogenesis of real tissues. In this paper, we propose a theoretical model to investigate the mechanobiological response of soft tissues undergoing stress-modulated growth. Linear stability analysis is first performed to elucidate the surface instability mechanism induced by stress-modulated volumetric growth. We further conduct finite element simulations to validate the theoretical prediction and, particularly, to capture the post-buckling pattern evolution. Our results show that the non-uniform stresses, which evolve with the tissue growth and morphogenesis, exert mechanical feedback on the growth itself, producing up-down asymmetric surface morphologies as observed in, for example, the gyrification of human brains and brain organoids. It is also revealed that large residual stresses are unnecessary to cause mechanobiological instability and subsequent asymmetric patterning, which has long been believed to be driven by sufficiently high stresses. The present work could help us to understand the morphological changes of biological tissues under physiological and pathological conditions.
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Modelos Biológicos , Modelos Teóricos , Humanos , Morfogênese , Estresse Mecânico , Análise de Elementos FinitosRESUMO
Rigidity of the extracellular matrix markedly regulates many cellular processes. However, how cells detect and respond to matrix rigidity remains incompletely understood. Here, we propose a unified two-dimensional multiscale framework accounting for the chemomechanical feedback to explore the interrelated cellular mechanosensing, polarization, and migration, which constitute the dynamic cascade in cellular response to matrix stiffness but are often modeled separately in previous theories. By combining integrin dynamics and intracellular force transduction, we show that substrate stiffness can act as a switch to activate or deactivate cell polarization. Our theory quantitatively reproduces rich stiffness-dependent cellular dynamics, including spreading, polarity selection, migration pattern, durotaxis, and even negative durotaxis, reported in a wide spectrum of cell types, and reconciles some inconsistent experimental observations. We find that a specific bipolarized mode can determine the optimal substrate stiffness, which enables the fastest cell migration rather than the largest traction forces that cells apply on the substrate. We identify that such a mechanical adaptation stems from the force balance across the whole cell. These findings could yield universal insights into various stiffness-mediated cellular processes within the context of tissue morphogenesis, wound healing, and cancer invasion.
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Matriz Extracelular , Adesões Focais , Movimento Celular , Matriz Extracelular/metabolismo , Adesões Focais/metabolismo , Integrinas/metabolismo , Fenômenos Mecânicos , Mecanotransdução CelularRESUMO
Growing axons are one-dimensional active structures that are important for wiring the brain and repairing nerves. However, the biophysical mechanisms underlying the complex kinetics of growing axons remain elusive. Here, we develop a theoretical framework to recapitulate force-regulated states and their transitions in growing axons. We demonstrate a unique negative feedback mechanism that defines four distinct kinetic states in a growing axon, whose transitional boundaries depend on the interplay between cytoskeletal dynamics and axon-substrate adhesion. A phase diagram for axonal growth is formulated based on two dimensionless numbers.
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Axônios , Encéfalo , Axônios/fisiologiaRESUMO
A falling liquid drop, after impact on a rigid substrate, deforms and spreads, owing to the normal reaction force. Subsequently, if the substrate is nonwetting, the drop retracts and then jumps off. As we show here, not only is the impact itself associated with a distinct peak in the temporal evolution of the normal force, but also the jump-off, which was hitherto unknown. We characterize both peaks and elucidate how they relate to the different stages of the drop impact process. The time at which the second peak appears coincides with the formation of a Worthington jet, emerging through flow focusing. Even low-velocity impacts can lead to a surprisingly high second peak in the normal force, even larger than the first one, namely when the Worthington jet becomes singular due to the collapse of an air cavity in the drop.
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Using atomic force microscopy, we have shown that friction on graphene/h-BN superlattice structures may exhibit unusual moiré-scale stick slip in addition to the regular ones observed at the atomic scale. Such dual-scale slip instability will lead to unique length-scale dependent energy dissipation when the different slip mechanisms are sequentially activated. Assisted by an improved theoretical model and comparative experiments, we find that accumulation and unstable release of the in-plane strain of the graphene layer is the key mechanism underlying the moiré-scale behavior. This work highlights the distinct role of the internal state of the van der Waals interfaces in determining the rich dynamics and energy dissipation of layer-structured materials.
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As a species of insects living on water, water striders jump from the water surface to avoid predation and then steadily land without piercing the surface. This spectacular property has attracted extensive interests since it provides bio-inspirations for designing functional microrobots moving on water. In this work, we investigate the landing dynamics of water striders by using artificial striders with different masses and leg lengths. It is found that once a water strider has landed, it oscillates on the water surface and the amplitude decays gradually, triggering a sequence of surface waves. Through scaling analysis, we relate the depth of the dimple that the strider leg displaces to its landing velocity, as well as its leg length and body mass. The subsequent time evolution of the interface where the strider lands is modeled as a damped oscillator, and its energy is exhausted by the surface waves. Moreover, we discuss the maximum depth of the dimple excited by the landing and find that the dynamic process can store more energy than the statically deforming process. Finally, we put forward a criterion of piercing the water surface from the energy point of view. These findings should be of great importance for understanding the locomotion of insects on water and for designing robust water-walking bionic robots.
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Heterópteros , Água , Animais , Insetos , Locomoção , Modelos TeóricosRESUMO
Controlling, and in many cases minimizing, friction is a goal that has long been pursued in history. From the classic Amontons-Coulomb law to the recent nanoscale experiments, the steady-state friction is found to be an inherent property of a sliding interface, which typically cannot be altered on demand. In this work, we show that the friction on a graphene sheet can be tuned reversibly by simple mechanical straining. In particular, by applying a tensile strain (up to 0.60%), we are able to achieve a superlubric state (coefficient of friction nearly 0.001) on a suspended graphene. Our atomistic simulations together with atomically resolved friction images reveal that the in-plane strain effectively modulates the flexibility of graphene. Consequently, the local pinning capability of the contact interface is changed, resulting in the unusual strain-dependent frictional behavior. This work demonstrates that the deformability of atomic-scale structures can provide an additional channel of regulating the friction of contact interfaces involving configurationally flexible materials.
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Fascin1 is known to participate in the migration of cancer cells by binding to actin filaments. Recent studies evidenced that fascin1 also modulates processes such as the tumorigenesis and maintenance of pluripotency genes in cancer stem cells. However, the function of fascin1 in embryonic stem cells remains unclear. In this article, we report that fascin1 is highly expressed and widely distributed in mouse embryonic stem cells (mESCs), which are regulated by JAK-STAT3 and ß-catenin. We found that the overexpression of fascin1 impairs the formation of mESC colonies via the downregulation of intercellular adhesion molecules, and that mimicking the dephosphorylated mutation of fascin1 or inhibiting phosphorylation with Gö6983 significantly enhances colony formation. Hyperphosphorylated fascin1 can promote the maintenance of pluripotency in mESCs via nuclear localization and suppressing DNA methyltransferase expression. Our findings demonstrate a novel function of fascin1, as a vital regulator, in the colony formation and pluripotency of mESCs and provide insights into the molecular mechanisms underlying embryonic stem cell self-organization and development in vitro.
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Proteínas dos Microfilamentos/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Receptores Odorantes/metabolismo , Animais , Linhagem Celular , Ensaio de Unidades Formadoras de Colônias , Metilação de DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Proteínas dos Microfilamentos/genética , Modelos Biológicos , Fosforilação , Receptores Odorantes/genéticaRESUMO
Turgor pressure and envelope elasticity of bacterial cells are two mechanical parameters that play a dominant role in cellular deformation, division, and motility. However, a clear understanding of these two properties is lacking because of their strongly interconnected mechanisms. This study established a nanoindentation method to precisely measure the turgor pressure and envelope elasticity of live bacteria. The indentation force-depth curves of Klebsiella pneumoniae bacteria were recorded with atomic force microscopy. Through combination of dimensional analysis and numerical simulations, an explicit expression was derived to decouple the two properties of individual bacteria from the nanoindentation curves. We show that the Young's modulus of bacterial envelope is sensitive to the external osmotic environment, and the turgor pressure is significantly dependent on the external osmotic stress. This method can not only quantify the turgor pressure and envelope elasticity of bacteria, but also help resolve the mechanical behaviors of bacteria in different environments.
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Klebsiella pneumoniae , Fenômenos Mecânicos , Elasticidade , Microscopia de Força Atômica , Pressão OsmóticaRESUMO
Friction between two solid surfaces often exhibits strong rate and slip-history dependence, which critically determines the dynamic stability of frictional sliding. Empirically, such an evolutional effect has been captured by the rate-and-state friction (RSF) law based on laboratory-scale experiments; but its applicability for generic sliding interfaces under different length scales remains unclear. In this Letter, frictional aging, the key manifestation of the evolutional behavior, of silica-silica contacts is studied via slide-hold-slide tests with apparent contact size spanning across 3 orders of magnitude. The experimental results demonstrate a clear and strong length scale dependency in frictional aging characteristics. Assisted by a multiasperity RSF model, we attribute the length scale effect to roughness-dependent true contact area evolution as well as scale-dependent friction stress due to nonconcurrent slip.
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Cellular dynamic behaviors in organ morphogenesis and embryogenesis are affected by geometrical constraints. In this paper, we investigate how the surface topology and curvature of the underlying substrate tailor collective cell migration. An active vertex model is developed to explore the collective dynamics of coherent cells crawling on curved surfaces. We show that cells can self-organize into rich dynamic patterns including local swirling, global rotation, spiral crawling, serpentine crawling, and directed migration, depending on the interplay between cell-cell interactions and geometric constraints. Increasing substrate curvature results in higher cell-cell bending energy and thus tends to suppress local swirling and enhance density fluctuations. Substrate topology is revealed to regulate both the collective migration modes and density fluctuations of cell populations. In addition, upon increasing noise intensity, a Kosterlitz-Thouless-like ordering transition can emerge on both undevelopable and developable surfaces. This study paves the way to investigate various in vivo morphomechanics that involve surface curvature and topology.
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Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant role in the systems' morphologies, it remains elusive whether and how the mechanical components may contribute to the systems' collective morphodynamics. Here, we study the collective oscillations in the Drosophila amnioserosa tissue to elucidate the regulatory roles of the mechanical components. We identify that the tensile stress is the key activator that switches the collective oscillations on and off. This regulatory role is shown analytically using the Hopf bifurcation theory. We find that the physical properties of the tissue boundary are directly responsible for synchronizing the oscillatory intensity and polarity of all inner cells and for orchestrating the spatial oscillation patterns inthe tissue.
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Drosophila/embriologia , Embrião não Mamífero/citologia , Modelos Biológicos , Animais , Fenômenos Biomecânicos , Embrião não Mamífero/metabolismo , Retroalimentação Fisiológica , Membrana Serosa/citologia , Membrana Serosa/metabolismo , Resistência à TraçãoRESUMO
Active particles capable of self-propulsion commonly exhibit rich collective dynamics and have attracted increasing attention due to their applications in biology, robotics, social transport, and biomedicine. However, it remains unclear how the geometric features of active particles affect their collective behaviors. In this paper, we explore the collective dynamics of L-shaped active rods. We show that a dense suspension of self-propelled L-shaped rods exhibits fascinating non-equilibrium oscillatory dynamic clustering. A new oscillation phase can form due to distinct collisions and aggregation mechanisms arising from the L-shaped chirality of elements. A generic diagram of emerging states is provided over a wide range of geometric parameters. Our findings show that the comparative strength between the periodic separation and proximity effect from chirality and the alignment effect from elongated geometry drive the formation and transition of dynamic patterns. This chirality-triggered oscillation phase suggests a new route to understand active matter and paves a way for emerging applications.
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Two-dimensional (2D) materials have seen a broad range of applications in electronic and optoelectronic applications; however, full realization of this potential hitherto largely hinges on the quality and performance of the electrical contacts formed between 2D materials and their surrounding metals/semiconductors. Despite the progress in revealing the charge injecting mechanisms and enhancing electrical conductance using various interfacial treatments, how the microstructure of contact interfaces affects local electrical conductivity is still very limited. Here, using conductive atomic force microscopy (c-AFM), for the first time, we directly confirm the conjecture that the electrical conductivity of physisorbed 2D material-metal/semiconductor interfaces is determined by the local electronic charge transfer. Using lattice-resolved conductivity mapping and first-principles calculations, we demonstrate that the electronic charge transfer, thereby electrical conductivity, can be fine-tuned by the topological defects of 2D materials and the atomic stacking with respect to the substrate. Our finding provides a novel route to engineer the electrical contact properties by exploiting fine atomic interactions; in the meantime, it also suggests a convenient and nondestructive means of probing subtle interactions along 2D heterogeneous interfaces.
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Mechanical cues from the microenvironments play a regulating role in many physiological and pathological processes, such as stem cell differentiation and cancer cell metastasis. Experiments showed that cells adhered on a compliant substrate may change orientation with an externally applied strain in the substrate. By accounting for actin polymerization, actin retrograde flow, and integrin binding dynamics, here we develop a mechanism-based tensegrity model to study the orientations of polarized cells on a compliant substrate under biaxial stretches. We show that the cell can actively regulate its mechanical state by generating different traction force levels along its polarized direction. Under static or ultralow-frequency cyclic stretches, stretching a softer substrate leads to a higher increase in the traction force and induces a narrower distribution of cell alignment. Compared to static loadings, high-frequency cyclic loadings have a more significant influence on cell reorientation on a stiff substrate. In addition, the width of the cellular angular distribution scales inversely with the stretch amplitude under both static and cyclic stretches. Our results are in agreement with a wide range of experimental observations, and provide fundamental insights into the functioning of cellular mechanosensing systems.