Three-dimensional Multiscale Model Research Articles

Study of impacts of two types of cellular aging on the yeast bud morphogenesis.

Understanding the mechanisms of the cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short cell cycle, and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. Recent experiments suggested the existence of two aging modes in yeast characterized by nucleolar and mitochondrial declines, respectively. By analyzing experimental data, this study shows that cells evolving into those two aging modes behave differently when they are young. While buds grow linearly in both modes, cells that consistently generate spherical buds throughout their lifespan demonstrate greater efficacy in controlling bud size and growth rate at young ages. A three-dimensional multiscale chemical-mechanical model was developed and used to suggest and test hypothesized impacts of aging on bud morphogenesis. Experimentally calibrated model simulations showed that during the early stage of budding, tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip, a process guided by the polarized Cdc42 signal. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage as observed in experiments in this work. The model simulation results suggest that the localization of new cell surface material insertion, regulated by chemical signal polarization, could be weakened due to cellular aging in yeast and other cell types, leading to the change and stabilization of the bud aspect ratio.

Effect of solutes on texture evolution during grain growth in ZK60 alloy by phase field simulation

A three-dimensional (3D) multiscale phase field model was proposed to investigate the effect of Ca, Y and Al solutes on the texture evolution of ZK60 alloy during grain growth at 573 K under an applied compression stress of 270 MPa, in which the characteristics of the elastic anisotropy and grain boundary (GB) segregation caused by the solutes were taken into account. The results show that either Ca or Y addition can weaken the basal texture of ZK60, while Al addition enhances it. The deviation of the grain size distribution from the Hillert model becomes greater with the addition of Al, while Ca or Y addition reduces the deviation. The solute segregation-induced GB energy change has a very limited effect on the texture evolution compared with elastic anisotropy. The revealed mechanism is of great significance for the microstructure design of the ZK60 alloy by an appropriate alloying strategy.

The effect of plasmin-mediated degradation on fibrinolysis and tissue plasminogen activator diffusion

We modify a three-dimensional multiscale model of fibrinolysis to study the effect of plasmin-mediated degradation of fibrin on tissue plasminogen activator (tPA) diffusion and fibrinolysis. We propose that tPA is released from a fibrin fiber by simple kinetic unbinding, as well as by “forced unbinding,” which occurs when plasmin degrades fibrin to which tPA is bound. We show that, if tPA is bound to a small-enough piece of fibrin that it can diffuse into the clot, then plasmin can increase the effective diffusion of tPA. If tPA is bound to larger fibrin degradation products (FDPs) that can only diffuse along the clot, then plasmin can decrease the effective diffusion of tPA. We find that lysis rates are fastest when tPA is bound to fibrin that can diffuse into the clot, and slowest when tPA is bound to FDPs that can only diffuse along the clot. Laboratory experiments confirm that FDPs can diffuse into a clot, and they support the model hypothesis that forced unbinding of tPA results in a mix of FDPs, such that tPA bound to FDPs can diffuse both into and along the clot. Regardless of how tPA is released from a fiber, a tPA mutant with a smaller dissociation constant results in slower lysis (because tPA binds strongly to fibrin), and a tPA mutant with a larger dissociation constant results in faster lysis.

Predictable Local Polarization inside Electrodes By Three-Dimensional Multi-Scale Model in Flow Batteries

Redox flow batteries (RFBs) are regarded as one of the most promising grid-scale energy storage technologies, which can improve the applicability of wind and solar energy by leveling their fluctuating power output. In RFBs, the gas side reactions including hydrogen evolution reaction and oxygen evolution reaction reduce the efficiency and capacity of the batteries and the gas produced may even cause safety problems. Even if the voltage is controlled in practical applications to restrict the gas side reactions, it is still inevitable due to flow dead zones or insufficient reactants locally inside the electrode. Gas side reactions are usually caused by too high local overpotential, i.e., local over polarization. Therefore, in this work, we propose a multi-scale model that allows the rapid prediction of local polarization to limit and manage the gas side reactions. The multi-scale model contains a deep neural network, a pore network model, and a three-dimensional continuum model with the advantages of both accuracy and extensibility. By learning from the sample data provided by the cell-scale model and the pore-scale model, the deep neural network can quickly predict the local polarization under different operating conditions and give the distribution map of the entire electrode. Compared with conventional models, multi-scale models can take into account the geometry of electrode fibers and are suitable for electrode design and modification. Due to the calculation superiority of the pore network model, the multi-scale model can realize three-dimensional local polarization prediction, which enables a more accurate analysis of the internal uniformity of the electrode. Through the developed model, we explore the effects of the interdigitated flow field, flow rate, initial concentration and voltage on local polarization. It is shown that the multi-scale model can accurately predict local polarization. However, the promotion of flow rate cannot completely eliminate the occurrence of local over polarization.

A multi-scale model for local polarization prediction in flow batteries based on deep neural network

The side reaction of the flow battery will consume electrons, reduce efficiency, and eventually cause safety problems. Regarding gas management and removal, carefully controlling local over-polarization is a vital issue. However, among the multi-scale models that can predict local polarization, the lack of dimensionality inside the electrode makes it impractical to predict three-dimensional variations. In this work, we propose a three-dimensional multi-scale model that allows the rapid prediction of local polarization, which cooperates with deep neural networks, the pore network model, and the three-dimensional continuum model to have both the advantages of accuracy and extensibility. Parameters such as the porosity, permeability, and specific surface area of the electrode are calculated from 500 randomly generated microstructures, and the training samples for the deep neural network are calculated by the cell-scale model and pore-scale model. Through the developed model, we explore the effects of the interdigitated flow field, variable flow rate optimization strategies, and diverse operating conditions on local polarization. The results show that the proposed model can accurately predict local polarization. The research directions of future work include the collaborative optimization of the electrode's microstructure, the flow field, and the flow rate to ultimately improve the local polarization uniformity.

Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots

While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction or retraction. Impairment of the clot contraction process is associated with both life-threatening bleeding and thrombotic conditions, such as ischemic stroke, venous thromboembolism, and others. Recently, blood clot contraction was observed to be hindered in patients with COVID-19. A three-dimensional multiscale computational model is developed and used to quantify biomechanical mechanisms of the kinetics of clot contraction driven by platelet-fibrin pulling interactions. These results provide important biological insights into contraction of platelet filopodia, the mechanically active thin protrusions of the plasma membrane, described previously as performing mostly a sensory function. The biomechanical mechanisms and modeling approach described can potentially apply to studying other systems in which cells are embedded in a filamentous network and exert forces on the extracellular matrix modulated by the substrate stiffness.

Chloride ion diffusion and distribution characteristics in recycled coarse aggregate concrete under uniaxial and biaxial pressure

Under uniaxial compression, recycled coarse aggregate leads to complex internal stresses (simultaneous uniaxial, biaxial, and multiaxial tensile and compressive stresses at the micro scale) and even micro cracks in concrete, which poses difficulties in accurately predicting the chloride ion diffusion of recycled concrete. By changing the compressive stress level and bi-directional stress ratio of concrete, a self-developed biaxial compression device was used to test the chloride ion diffusion coefficient of recycled concrete under different stress states. In order to analyze the influence of various factors on chloride ion diffusion, DIC digital image technology and microcrack statistics technology were used to analyze the influence of concrete micro deformation on its chloride ion diffusion coefficient under load, and X-ray fluorescence technology was used to accurately analyze the concentration distribution of chloride element in different positions of concrete. The pore structure inside recycled concrete was characterized through experiments, and a real three-dimensional multi-scale model of concrete and the statistical characteristics of porosity at different scales were obtained. Finally, a theoretical model was established to predict the chloride ion diffusion coefficient under biaxial compressive loads, achieving accurate prediction of chloride ion diffusion coefficient close to practical engineering.

Multiscale Finite-Element Analysis of Damage Behavior of Curved Ramp Bridge Deck Pavement Considering Tire–Bridge Interaction Effect

The present study developed a three-dimensional (3D) multiscale modeling approach to investigate the mesoscale damage behavior of curved ramp bridge deck pavement subjected to tire loading. First, a full-scale tire–bridge interaction finite element (FE) model was established to solve the macroscopic response of deck pavement during vehicle turning. Subsequently, the 3D mesostructure of the asphalt concrete layer was reconstructed from X-ray computer tomography (CT) images through a digital image processing (DIP) technology. Finally, a homogenization method was adopted to link the mechanical properties of deck pavement at two different scales, and a mapping procedure was employed to transfer the boundary displacements from macroscale pavement target element to the mesoscale representative volume element (RVE) model. Also, the bilinear cohesive elements were applied to simulate damage initiation in the RVEs. The results showed that smaller curvature radius and higher travel speed can promote unbalanced stress and local damage of the outer loading zone. From the mesoscale viewpoint, reducing curvature radius or increasing travel speed could result in crack direction shifts and increase the irregularity of microcrack distribution. In addition, transverse microcracks are commonly found in the center of the tire load, while longitudinal microcracks are distributed on the deck pavement surface around the tire edges and the dual-tire clearance center.

Light-induced swirling and locomotion

The design of remotely activated, untethered devices without onboard power is a continuing challenge in soft robotics. This work describes a method of generating a whirling motion in pre-stressed photomechanical liquid crystal elastomer fibres using steady illumination that can be exploited for propulsion and mixing. Photomechanical liquid crystal elastomers (LCEs) can convert light directly into mechanical deformation, making them attractive candidates for soft actuators capable of remote and multi-mode actuation. We propose a three-dimensional multi-scale model of the nonlinear and non-local dynamics of fibres of photomechanical LCEs under illumination. We use the model to show that pre-stressed helix-like fibres immersed in a fluid can undergo a periodic whirling motion under steady illumination. We analyse the photo-driven spatio-temporal pattern and stability of the whirling deformation, and provide a parametric study. Unlike previous work on photo-driven periodic motion, this whirling motion does not exploit instabilities in the form of snap-through phenomena, or unilateral constraints as in rolling. More broadly, our work provides an unusual example of a physical system capable of periodic motion under steady stimulus that does not exploit instabilities. We finally show that such motion can be exploited in developing remote controlled bioinspired microswimmers and novel micromixers.

A three-dimensional multiscale model for the prediction of thrombus growth under flow with single-platelet resolution.

Modeling thrombus growth in pathological flows allows evaluation of risk under patient-specific pharmacological, hematological, and hemodynamical conditions. We have developed a 3D multiscale framework for the prediction of thrombus growth under flow on a spatially resolved surface presenting collagen and tissue factor (TF). The multiscale framework is composed of four coupled modules: a Neural Network (NN) that accounts for platelet signaling, a Lattice Kinetic Monte Carlo (LKMC) simulation for tracking platelet positions, a Finite Volume Method (FVM) simulator for solving convection-diffusion-reaction equations describing agonist release and transport, and a Lattice Boltzmann (LB) flow solver for computing the blood flow field over the growing thrombus. A reduced model of the coagulation cascade was embedded into the framework to account for TF-driven thrombin production. The 3D model was first tested against in vitro microfluidics experiments of whole blood perfusion with various antiplatelet agents targeting COX-1, P2Y1, or the IP receptor. The model was able to accurately capture the evolution and morphology of the growing thrombus. Certain problems of 2D models for thrombus growth (artifactual dendritic growth) were naturally avoided with realistic trajectories of platelets in 3D flow. The generalizability of the 3D multiscale solver enabled simulations of important clinical situations, such as cylindrical blood vessels and acute flow narrowing (stenosis). Enhanced platelet-platelet bonding at pathologically high shear rates (e.g., von Willebrand factor unfolding) was required for accurately describing thrombus growth in stenotic flows. Overall, the approach allows consideration of patient-specific platelet signaling and vascular geometry for the prediction of thrombotic episodes.

Analyzing Effects of Mesostructure of Composite Electrode on Performance of Intermediate-Temperature Solid Oxide Electrolysis Cell Using a Three-Dimensional Multi-Scale Mathematical Model

Analyzing Effects of Mesostructure of Composite Electrode on Performance of Intermediate-Temperature Solid Oxide Electrolysis Cell Using a Three-Dimensional Multi-Scale Mathematical Model

The sealing mechanism of radial lip seals: A numerical study of the tangential distortion of the sealing edge

The sealing behaviour of elastomeric radial lip seals is essentially affected by the sealing mechanism in the contact area between the sealing edge and the shaft surface. The relative motion between radial lip seal and shaft deforms the sealing edge tangentially in the circumferential direction. This mechanical deformation is considered essential for the sealing mechanism. In this study, a numerical approach is employed to simulate this deformation. A three-dimensional multiscale model serves this purpose. The radial lip seal geometry is described on the macro-scale. On the micro-scale, an artificial rough surface with a stochastic roughness distribution is applied to an ideal sealing edge surface. A new meshing algorithm is used to discretise different sealing edge surfaces and automatically generates structured hexahedral meshes of the sealing edges. Mesh transitions connect the resulting finely meshed sealing edge to the coarsely meshed global macro-scale mesh of the radial lip seal. The paper introduces the modelling method used to simulate the deformation of radial lip seals. Results are presented and discussed with reference to the sealing behaviour. This contributes to a better understanding of the sealing mechanism of radial lip seals. Keywords: radial lip seal, finite element analysis, surface roughness, elastic deformation, elastomers.

Wear on radial lip seals: a numerical study of the influence on the sealing mechanism

In this paper a numerical approach is applied to analyse the influence of wear on the lubrication and sealing mechanism of radial lip seals. A three-dimensional multi-scale mechanical model is presented. This allows to simulate the macroscopic deformation of the entire radial lip seal and the microscopic deformations in the contact area between the sealing edge and the shaft surface. Furthermore, different wear band widths and surface roughness of sealing edges can be analysed efficiently. In the context of this paper, measurement results of radial lip seals in different wear states out of test runs are applied. The simulation results of the different sealing edges are compared. This allows drawing conclusions about the influence of wear on the performance of radial lip seals. This leads to a better understanding of the potential failure mechanisms of radial lip seals.

A multiscale framework for evaluating three-dimensional cell mechanics in fibril-reinforced poroelastic tissues with anatomical cell distribution – Analysis of chondrocyte deformation behavior in mechanically loaded articular cartilage

Characterization of the mechanical environment of cells in collagenous biological tissues during different daily activities is crucial for understanding the role of mechanics on cell biosynthesis and tissue health. However, current imaging methods are limited in characterizing very fast deformations of cells. This could be achieved with computational multiscale modeling, but current models accommodating collagen fibril networks and poroelastic ground matrix have included only a single cell. In this study, a workflow was developed for generating a three-dimensional multiscale model with imaging-based anatomical cell distributions and their micro-environment (pericellular and extracellular matrix). Fibril-reinforced poroelastic material models with (FRPES) and without (FRPE) swelling were implemented into the model and simulations were performed for evaluating cell deformations before and after experimental loading conducted for rabbit knee joint cartilage. We observed that the cells experienced considerably different deformation based on their location in all models. Both FRPE and FRPES models were able to predict the trends in the changes in cell deformations, although the average and median magnitudes differed between the model predictions and experiments. However, the FRPES model results were generally closer to the experimental results. Current findings suggest that morphological properties of cells are affected by the variations in the tissue properties between the samples and variations within the sample caused by the measurement geometry, local structure and composition. Thus, it would be important to consider the anatomical distribution and location of multiple cells along with the structure of fibril networks if cell deformation metrics are evaluated in collagenous tissues.

Multiscale Modeling of Fiber Fragmentation Process in Aligned ZnO Nanowires Enhanced Single Fiber Composites

A three-dimensional multiscale modeling framework is developed to analyze the failure procedure of radially aligned zinc oxide (ZnO) enhanced single fiber composites (SFC) under tensile loading to understand the interfacial improvement between the fiber and the matrix. The model introduces four levels in the computational domain. The nanoscale analysis calculates the size-dependent material properties of ZnO nanowires. The interaction between ZnO nanowires and the matrix is simulated using a properly designed representative volume element at the microscale. At the mesoscale, the interface between the carbon fiber and the surrounding area is modeled using the cohesive zone approach. A combination of ABAQUS Finite element software and the failure criteria modeled in UMAT user subroutine is implemented to simulate the single fiber fragmentation test (SFFT) at the macroscale. The numerical results indicate that the interfacial shear strength of SFC can be improved up to 99% after growing ZnO nanowires on the fiber. The effect of ZnO nanowires geometries on the interfacial shear strength of the enhanced SFC is also investigated. Experimental ZnO nanowires enhanced SFFTs are performed on the fabricated samples to validate the results of the developed multiscale model. A good agreement between the numerical and the experimental results was observed.

A multiscale modeling for failure predictions of fiber reinforced composite laminates

A three-dimensional multiscale damage modeling, based on the parametric High Fidelity Generalized Method of Cells (HFGMC) micromechanics and integrated with a finite-element (FE) code, is proposed to predict the mechanical response, including damage evolution, as well as to generate failure envelopes of composite laminates. A hexagonal repeating unit-cell (RUC) is used to represent explicitly the fiber and matrix phases of a lamina at the microscale level. Failure of a lamina is determined by using both strain-based and stress-based failure theories. This modeling approach is implemented as a user material subroutine (UMAT) within displacement-based Solid FE models, where each solid element is represented by one material point. When the modeled damage is propagating within the macroscale FE model, the material points are eliminated from the FE calculations by using the element deletion approach. The efficiency of the proposed multiscale modeling is demonstrated by a comparison of simulated results with measured data available in the literature.

Strength Properties of Metal–Intermetallic Laminated Composites in Three-Dimensional Model

The paper studies the instability of the plastic flow and fracture of metal-intermetallic laminated composites using a three-dimensional multi-scale model of the dislocation kinetics and mechanics of the elastoplastic medium under the dynamic high-temperature compression. The suggested theoretical stress-strain curves represent the behavior of laminated composites at different deformation temperatures and layer arrangements. It is shown that the inclusion of soft plastic metallic layers into the intermetallic matrix stabilizes the plastic flow of laminated composites, significantly increases the plasticity and time to fracture and decreases the deformation resistance. The layer arrangement has no great effect on the stability of plastic deformation.

Grain boundary effect on nanoindentation: A multiscale discrete dislocation dynamics model

Nanoindentation is a convenient method to investigate the mechanical properties of materials on small scales by utilizing low loads and small indentation depths. However, the effect of grain boundaries (GBs) on the nanoindentation response remains unclear and needs to be studied by investigating in detail the interactions between dislocations and GBs during nanoindentation. In the present work, we employ a three-dimensional multiscale modeling framework, which couples three-dimensional discrete dislocation dynamics (DDD) with the Finite Element method (FEM) to investigate GB effects on the nanoindentation behavior of an aluminum bicrystal. The interaction between dislocations and GB is physically modeled in terms of a penetrable GB, where piled-up dislocations can penetrate through the GB and dislocation debris at GBs can emit full dislocations into grains. In the simulation, we confirmed two experimentally observed phenomena, namely, pop-in events and the dependence of indentation hardness on the distance from GB. Two pop-in events were observed, of which the initial pop-in event is correlated with the activation and multiplication of dislocations, while the GB pop-in event results from dislocation transmission through the GB. By changing the distance between the indenter and GB, the simulation shows that the indentation hardness increases with decreasing GB-indenter distance. A quantitative model has been formulated which relates the dependency of indentation hardness on indentation depth and on GB-indenter distance to the back stress created by piled-up geometrically necessary dislocations in the plastic zone and to the additional constraint imposed by the GB on the plastic zone size.

Understanding the mechanical link between oriented cell division and cerebellar morphogenesis

The cerebellum is a tightly folded structure located at the back of the head. Unlike the folds of the cerebrum, the folds of the cerebellum are aligned such that the external surface appears to be covered in parallel grooves. Experiments have shown that anchoring center initiation drives cerebellar foliation. However, the mechanism guiding the location of these anchoring centers, and subsequently cerebellar morphology, remains poorly understood. In particular, there is no definitive mechanistic explanation for the preferential emergence of parallel folds instead of an irregular folding pattern like in the cerebral cortex. Here we use mechanical modeling on the cellular and tissue scales to show that the oriented granule cell division observed in the experimental setting leads to the characteristic parallel folding pattern of the cerebellum. Specifically, we propose an agent-based model of cell clones, a strategy for propagating information from our in silico cell clones to the tissue scale, and an analytical solution backed by numerical results to understand how differential growth between the cerebellar layers drives geometric instability in three dimensional space on the tissue scale. This proposed mechanical model provides further insight into the process of anchoring center initiation and establishes a framework for future multiscale mechanical analysis of developing organs.

The Influence of Rotary Blood Pump Speed Modulation on the Risk of Intraventricular Thrombosis.

Rotary left ventricular assist devices (LVADs) are commonly operated at a constant speed, attenuating blood flow pulsatility. Speed modulation of rotary LVADs has been demonstrated to improve vascular pulsatility and pump washout. The effect of LVAD speed modulation on intraventricular flow dynamics is not well understood, which may have an influence on thromboembolic events. This study aimed to numerically evaluate intraventricular flow characteristics with a speed modulated LVAD. A severely dilated anatomical left ventricle was supported by a HeartWare HVAD in a three-dimensional multiscale computational fluid dynamics model. Three LVAD operating scenarios were evaluated: constant speed and sinusoidal co- and counter-pulsation. In all operating scenarios, the mean pump speed was set to restore the cardiac output to 5.0L/min. Co- and counter-pulsation was speed modulated with an amplitude of 750rpm. The risk of thrombosis was evaluated based on blood residence time, ventricular washout, kinetic energy densities, and a pulsatility index map. Blood residence time for co-pulsation was on average 1.8 and 3.7% lower than constant speed and counter-pulsation mode, respectively. After introducing fresh blood to displace preexisting blood for 10 cardiac cycles, co-pulsation had 1.5% less old blood in comparison to counter-pulsation. Apical energy densities were 84 and 27% higher for co-pulsation in comparison to counter-pulsation and constant speed mode, respectively. Co-pulsation had an increased pulsatility index around the left ventricular outflow tract and mid-ventricle. Improved flow dynamics with co-pulsation was caused by increased E-wave velocities which minimized blood stasis. In the studied scenario and from the perspective of intraventricular flow dynamics, co-pulsation of rotary LVADs could minimize the risk of intraventricular thrombosis.