Polymerization force-regulated actin filament-Arp2/3 complex interaction dominates self-adaptive cell migrations.

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.

Efficient network-matrix architecture for general flow transport inspired by natural pinnate leaves.

Networks embedded in three dimensional matrices are beneficial to deliver physical flows to the matrices. Leaf architectures, pervasive natural network-matrix architectures, endow leaves with high transpiration rates and low water pressure drops, providing inspiration for efficient network-matrix architectures. In this study, the network-matrix model for general flow transport inspired by natural pinnate leaves is investigated analytically. The results indicate that the optimal network structure inspired by natural pinnate leaves can greatly reduce the maximum potential drop and the total potential drop caused by the flow through the network while maximizing the total flow rate through the matrix. These results can be used to design efficient networks in network-matrix architectures for a variety of practical applications, such as tissue engineering, cell culture, photovoltaic devices and heat transfer.

Design of novel triply periodic minimal surface (TPMS) bone scaffold with multi-functional pores: lower stress shielding and higher mass transport capacity.

Background: The bone repair requires the bone scaffolds to meet various mechanical and biological requirements, which makes the design of bone scaffolds a challenging problem. Novel triply periodic minimal surface (TPMS)-based bone scaffolds were designed in this study to improve the mechanical and biological performances simultaneously. Methods: The novel bone scaffolds were designed by adding optimization-guided multi-functional pores to the original scaffolds, and finite element (FE) method was used to evaluate the performances of the novel scaffolds. In addition, the novel scaffolds were fabricated by additive manufacturing (AM) and mechanical experiments were performed to evaluate the performances. Results: The FE results demonstrated the improvement in performance: the elastic modulus reduced from 5.01 GPa (original scaffold) to 2.30 GPa (novel designed scaffold), resulting in lower stress shielding; the permeability increased from 8.58 × 10-9 m2 (original scaffold) to 5.14 × 10-8 m2 (novel designed scaffold), resulting in higher mass transport capacity. Conclusion: In summary, the novel TPMS scaffolds with multi-functional pores simultaneously improve the mechanical and biological performances, making them ideal candidates for bone repair. Furthermore, the novel scaffolds expanded the design domain of TPMS-based bone scaffolds, providing a promising new method for the design of high-performance bone scaffolds.

Predicting the effective compressive modulus of human cancellous bone using the convolutional neural network method.

The efficient prediction of biomechanical properties of bone plays an important role in the assessment of bone quality. However, the present techniques are either of low accuracy or of high complexity for the clinical application. The present study aims to investigate the predictive ability of the evolving convolutional neural network (CNN) technique in predicting the effective compressive modulus of porous bone structures. The T11/T12/L1 segments of thirty-five female cadavers were scanned using the HR-pQCT scanner and the images obtained from it were used to generate 10896 2 D bone samples, in which only the cancellous bony parts were processed and investigated. The corresponding 10896 heterogeneous finite-element (FE) models were generated, and then a CNN model was constructed and trained using the predictions of the FE analysis as the ground truths. Then the remaining 260 bone samples generated from the initial HR-pQCT images were used to test the predictive power of the CNN model. The results show that the coefficient of the determinant (R2) from the linear correlation between the CNN and FE predicted elastic modulus is 0.95, which is much higher than that from the correlation between the BMD and the FE predictions (R2 = 0.65). Furthermore, the 95th and 50th percentiles of relative prediction error are below 0.28 and 0.09, respectively. In the conclusion, the CNN model can efficiently predict the effective compressive modulus of human cancellous bone and can be used as a promising and clinically applicable method to evaluate the mechanical quality of porous bone.

A Review of the Mechanical Properties of Graphene Aerogel Materials: Experimental Measurements and Computer Simulations.

Graphene aerogels (GAs) combine the unique properties of two-dimensional graphene with the structural characteristics of microscale porous materials, exhibiting ultralight, ultra-strength, and ultra-tough properties. GAs are a type of promising carbon-based metamaterials suitable for harsh environments in aerospace, military, and energy-related fields. However, there are still some challenges in the application of graphene aerogel (GA) materials, which requires an in-depth understanding of the mechanical properties of GAs and the associated enhancement mechanisms. This review first presents experimental research works related to the mechanical properties of GAs in recent years and identifies the key parameters that dominate the mechanical properties of GAs in different situations. Then, simulation works on the mechanical properties of GAs are reviewed, the deformation mechanisms are discussed, and the advantages and limitations are summarized. Finally, an outlook on the potential directions and main challenges is provided for future studies in the mechanical properties of GA materials.

Retraction notice to influence of nucleotomy on the load sharing in the spinal facet joint under the loading scenarios of different human postures.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. The authors have failed to cite or to acknowledge prior work appropriately. (The author of that prior work preferred for its details not to be included in this notice.) One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited.

Delayed reorganisation of F-actin cytoskeleton and reversible chromatin condensation in scleral fibroblasts under simulated pathological strain.

Mechanical loading regulates the functional capabilities of the ocular system, particularly in the sclera ('white of the eye') - the principal load-bearing tissue of the ocular globe. Resident fibroblasts of the scleral eye wall are continuously subjected to fluctuating mechanical strains arising from eye movements, cerebrospinal fluid pressure and, most influentially, intra-ocular pressure (IOP). Whilst fibroblasts are hypothesised to actively participate in scleral biomechanics, to date limited information has been reported on how the macroscopic stresses and strains are transmitted via their cytoskeletal networks. In this study, the effect of applying either a 'physiological load' (simulating healthy IOP) or a 'pathological load' (simulating an elevated glaucomatous IOP) to bovine scleral fibroblasts, as a model of human glaucoma, was conducted to characterise cytoskeletal organisation, chromatin condensation and cell dimensions using immunofluorescence confocal microscopy. Quantification of cell parameters and cytoskeletal element anisotropy were subsequently performed using FibrilTool, and chromatin condensation parameter assessment through a bespoke MATLAB script. The novel findings suggest that physiological load-induced F-actin rearrangement is transient, whereas pathological load, recapitulating in vivo glaucomatous IOP levels, had a reversible and inhibitory influence on remodelling of the cytoskeletal architecture and, further, induction of chromatin condensation. Ultimately, this could compromise cell behaviour. These findings could provide valuable insight into the mechanism(s) used by scleral fibroblasts to mechanically adapt to support biomechanical tissue integrity, and how it could be potentially modified for therapeutic avenues targeting mechanically mediated ocular pathologies such as glaucoma.

Comparison of the design maps of TPMS based bone scaffolds using a computational modeling framework simultaneously considering various conditions.

In recent years, the triply periodic minimal surface (TPMS)-based scaffolds have been served as one of the crucial types of structures for biological replacements, the energy absorber, etc. Meanwhile, the development of additive manufacturing (AM) has facilitated the production of TPMS scaffolds with complex microstructures. However, the design maps of TPMS scaffolds, especially considering the AM constraints, remain unclear, which has hindered the design and application of TPMS scaffolds. The aims of the present study were to develop an efficient computational modeling framework for investigating the design maps of TPMS scaffolds simultaneously considering the AM constraints, the biological requirements, and the structural anisotropy. To demonstrate the computational framework, five widely-used topologies of the TPMS-based scaffolds (i.e. the Diamond, the Gyroid, the Fischer-Koch S, the F-RD, and the Schwarz P) were used, whose design maps for the surface-to-volume ratio and the effective elastic modulus were also investigated. The results showed that as the porosities increase, the design ranges of the surface-to-volume ratios decreases for all the structures. Compared with the effect of the constraint for the pore size, the minimal structural thickness for AM constraint has a greater effect on the surface-to-volume ratio. Regarding the elastic modulus, in the region of low porosity (approximately 0.5-0.7), the range for the effective elastic modulus of Schwarz P is the widest (approximately 2.24-32.6 GPa), but the Gyroid can achieve both high porosity and low effective elastic modulus (e.g. 0.61 GPa at the porosity of 0.90). These results and the method developed in the present study provided important basis and guidance for the design and application of the TPMS-based porous structures.

Designing anisotropic porous bone scaffolds using a self-learning convolutional neural network model.

The design of bionic bone scaffolds to mimic the behaviors of native bone tissue is crucial in clinical application, but such design is very challenging due to the complex behaviors of native bone tissues. In the present study, bionic bone scaffolds with the anisotropic mechanical properties similar to those of native bone tissues were successfully designed using a novel self-learning convolutional neural network (CNN) framework. The anisotropic mechanical property of bone was first calculated from the CT images of bone tissues. The CNN model constructed was trained and validated using the predictions from the heterogonous finite element (FE) models. The CNN model was then used to design the scaffold with the elasticity matrix matched to that of the replaced bone tissues. For the comparison, the bone scaffold was also designed using the conventional method. The results showed that the mechanical properties of scaffolds designed using the CNN model are closer to those of native bone tissues. In conclusion, the self-learning CNN framework can be used to design the anisotropic bone scaffolds and has a great potential in the clinical application.

Hydrogen evolution via sunlight water splitting on an artificial butterfly wing architecture.

A prototype of nature's butterfly wing architecture using Pt loaded TiO(2) is provided and demonstrated to be able to enhance the hydrogen evolution rate by 2.3 times in sunlight water splitting. This is due to advantages brought about by the hierarchical architecture in both meso scope and nano scope.

Influence of nucleotomy on the load sharing in the spinal facet joint under the loading scenarios of different human postures.

One-in-five people suffer from chronic low back pain (LBP). The incidence of this disease has doubled since 1950s and affects not only the elderly, but also the young population. However, the mechanism of LBP is still unknown. A possible location where the LBP may develop is the facet joint and it has been revealed that the intervertebral disc (IVD) nucleotomy may be a trigger for LBP. The aim of the present study was to investigate the influence of IVD nucleotomy on the load sharing in the spinal facet joint under the loading scenarios of different postures. Finite element (FE) models of the intact and nucleotomised L4 - L5 spinal segments were generated from the clinical CT images. Seven human postures, including upright, 5° extension, 5° flexion, ± 6° lateral bending and ± 2° axial rotation, were simulated. The resultant forces in the fact joint were compared between the intact and the nucleotomised cases. It was revealed that the IVD nucleotomy significantly increased the forces in the facet joints under the loading scenarios of upright, 5° extension and 5° flexion. The IVD nucleotomy increased the force in the ipsilateral facet joint but decreased the force on the contralateral side under the loading scenarios of ± 2° axial rotation. However, the IVD nucleotomy made little influence on the resultant forces in both facet joints in the postures of ± 6° lateral bending. In conclusion, the IVD nucleotomy can cause an increase in the overall force in the facet joint, and thus may serve as a possible explanation for the LBP and a main contributing factor for the pain complaints.

3D immuno-confocal image reconstruction of fibroblast cytoskeleton and nucleus architecture.

Computational models of cellular structures generally rely on simplifying approximations and assumptions that limit biological accuracy. This study presents a comprehensive image processing pipeline for creating unified three-dimensional (3D) reconstructions of the cell cytoskeletal networks and nuclei. Confocal image stacks of these cellular structures were reconstructed to 3D isosurfaces (Imaris), then tessellations were simplified to reduce the number of elements in initial meshes by applying quadric edge collapse decimation with preserved topology boundaries (MeshLab). Geometries were remeshed to ensure uniformity (Instant Meshes) and the resulting 3D meshes exported (ABAQUS) for downstream application. The protocol has been applied successfully to fibroblast cytoskeletal reorganisation in the scleral connective tissue of the eye, under mechanical load that mimics internal eye pressure. While the method herein is specifically employed to reconstruct immunofluorescent confocal imaging data, it is also more widely applicable to other biological imaging modalities where accurate 3D cell structures are required.

Relationship between the morphological, mechanical and permeability properties of porous bone scaffolds and the underlying microstructure.

Bone scaffolds are widely used as one of the main bone substitute materials. However, many bone scaffold microstructure topologies exist and it is still unclear which topology to use when designing scaffold for a specific application. The aim of the present study was to reveal the mechanism of the microstructure-driven performance of bone scaffold and thus to provide guideline on scaffold design. Finite element (FE) models of five TPMS (Diamond, Gyroid, Schwarz P, Fischer-Koch S and F-RD) and three traditional (Cube, FD-Cube and Octa) scaffolds were generated. The effective compressive and shear moduli of scaffolds were calculated from the mechanical analysis using the FE unit cell models with the periodic boundary condition. The scaffold permeability was calculated from the computational fluid dynamics (CFD) analysis using the 4×4×4 FE models. It is revealed that the surface-to-volume ratio of the Fischer-Koch S-based scaffold is the highest among the scaffolds investigated. The mechanical analysis revealed that the bending deformation dominated structures (e.g., the Diamond, the Gyroid, the Schwarz P) have higher effective shear moduli. The stretching deformation dominated structures (e.g., the Schwarz P, the Cube) have higher effective compressive moduli. For all the scaffolds, when the same amount of change in scaffold porosity is made, the corresponding change in the scaffold relative shear modulus is larger than that in the relative compressive modulus. The CFD analysis revealed that the structures with the simple and straight pores (e.g., Cube) have higher permeability than the structures with the complex pores (e.g., Fischer-Koch S). The main contribution of the present study is that the relationship between scaffold properties and the underlying microstructure is systematically investigated and thus some guidelines on the design of bone scaffolds are provided, for example, in the scenario where a high surface-to-volume ratio is required, it is suggested to use the Fischer-Koch S based scaffold.

The elastic properties and deformation mechanisms of actin filament networks crosslinked by filamins.

As a substructure of cell cytoskeleton, the crosslinked actin filament networks (CAFNs) play a major role in different cell functions, however, the elastic properties and the deformation mechanisms of CAFNs still remain to be understood. In this paper, a novel three-dimensional (3D) finite element (FE) model has been developed to mimic the mechanical properties of actin filament (F-actin) networks crosslinked by filamin A (FLNA). The simulation results indicate that although the Young's modulus of CAFNs varies in different directions for each random model, the statistical mean value is in-plane isotropic. The crosslinking density and the actin filament volume fraction are found to strongly affect the in-plane shear modulus of CAFNs. The simulation results agree well with the relevant experimental results. In addition, an L-shaped cantilever beam model has been developed for dimensional analysis on the shear stiffness of CAFNs and for quantifying the deformation mechanisms. It has been demonstrated that the in-plane shear modulus of CAFNs is mainly dominated by FLNA (i.e., cross-linkers), and that the bending and torsion deformations of FLNA have almost the same contribution to the stiffness of CAFNs. It has also been found that the stiffness of CAFNs is almost insensitive to the variation of the Poisson's ratios of FLNA and actin filament in the range from 0.29 to 0.499.

Quantifying the discrepancies in the geometric and mechanical properties of the theoretically designed and additively manufactured scaffolds.

In recent years, the triply periodic minimal surface (TPMS) has emerged as a new method for producing open cell porous scaffolds because of the superior properties, such as the high surface-to-volume ratio, the zero curvature, etc. On the other hand, the additive manufacturing (AM) technique has made feasible the design and development of TPMS scaffolds with complex microstructures. However, neither the discrepancy between the theoretically designed and the additively manufactured TPMS scaffolds nor the underlying mechanisms is clear so far. The aims of the present study were to quantify the discrepancies between the theoretically designed and the AM produced TPMS scaffolds and to reveal the underlying mechanisms, e.g., the effect of building orientation on the discrepancy. 24 Gyroid scaffolds were produced along the height and width directions of the scaffold using the selective laser melting (SLM) technique (i.e., 12 scaffolds produced in each direction). The discrepancies in the geometric and mechanical properties of the TPMS scaffolds were quantified. Regarding the geometric properties, the discrepancies in the porosity, the dimension and the three-dimensional (3D) geometry of the scaffolds were quantified. Regarding the mechanical properties, the discrepancies in the effective compressive modulus and the mechanical environment (strain energy density) of the scaffolds were evaluated. It is revealed that the porosity in the AM produced scaffold is approximately 12% lower than the designed value. There are approximately 68.1 ± 8.6% added materials in the AM produced scaffolds and the added materials are mostly distributed in the places opposite to the building orientation. The building orientation has no effect on the discrepancy in the scaffold porosity and no effect on the distribution of the added materials (p > 0.05). Regarding the mechanical properties, the compressive moduli of the scaffolds are 24.4% (produced along the height direction) and 14.6% (produced along the width direction) lower than the designed value and are 49.1% and 43.6% lower than the µFE counterparts, indicating that the imperfect bonding and the partially melted powders have a large contribution to the discrepancy in the compressive modulus of the scaffolds. Compared to the values in the theoretically designed scaffold, the strain energy densities have shifted towards the higher values in the AM produced scaffolds. The findings in the present study provide important information for the design and additive manufacturing of TPMS scaffolds.

Predictive assembling model reveals the self-adaptive elastic properties of lamellipodial actin networks for cell migration.

Branched actin network supports cell migration through extracellular microenvironments. However, it is unknown how intracellular proteins adapt the elastic properties of the network to the highly varying extracellular resistance. Here we develop a three-dimensional assembling model to simulate the realistic self-assembling process of the network by encompassing intracellular proteins and their dynamic interactions. Combining this multiscale model with finite element method, we reveal that the network can not only sense the variation of extracellular resistance but also self-adapt its elastic properties through remodeling with intracellular proteins. Such resistance-adaptive elastic behaviours are versatile and essential in supporting cell migration through varying extracellular microenvironments. The bending deformation mechanism and anisotropic Poisson's ratios determine why lamellipodia persistently evolve into sheet-like structures. Our predictions are confirmed by published experiments. The revealed self-adaptive elastic properties of the networks are also applicable to the endocytosis, phagocytosis, vesicle trafficking, intracellular pathogen transport and dendritic spine formation.

Effect of parathyroid hormone on the structural, densitometric and failure behaviors of mouse tibia in the spatiotemporal space.

Parathyroid hormone (PTH) is an anabolic bone drug approved by the US Food and Drug Administration (FDA) to treat osteoporosis. However, previous studies using cross-sectional designs have reported variable and sometimes contradictory results. The aim of the present study was to quantify the localized effect of PTH on the structural and densitometric behaviors of mouse tibia and their links with the global mechanical behavior of bone using a novel spatiotemporal image analysis approach and a finite element analysis technique. Twelve female C57BL/6J mice were divided into two groups: the control and PTH treated groups. The entire right tibiae were imaged using an in vivo micro-computed tomography (µCT) system eight consecutive times. Next, the in vivo longitudinal tibial µCT images were rigidly registered and divided into 10 compartments across the entire tibial space. The bone volume (BV), bone mineral content (BMC), bone tissue mineral density (TMD), and tibial endosteal and periosteal areas (TEA and TPA) were quantified in each compartment. Additionally, finite element models of all the tibiae were generated to analyze the failure behavior of the tibia. It was found that both the BMC and BV started to increase in the proximal tibial region, and then the increases extended to the entire tibial region after two weeks of treatment (p < 0.05). PTH intervention significantly reduced the TEA in most tibial compartments after two weeks of treatment, and the TPA increased in most tibial regions after four weeks of treatment (p < 0.05). Tibial failure loads significantly increased after three weeks of PTH treatment (p < 0.01). The present study provided the first evidence of the localized effect of PTH on bone structural and densitometric properties, as well as their links with the global mechanical behaviors of bone, which are important pieces of information for unveiling the mechanism of PTH intervention.

The anisotropic elastic behavior of the widely-used triply-periodic minimal surface based scaffolds.

The Triple Periodic Minimal Surface (TPMS) has emerged as a new approach for producing open cell porous scaffolds for biomedical applications. However, different from the traditional scaffolds, the TPMS scaffolds always exhibit anisotropic elastic behaviors and consequently the simple mechanical testing is not capable to provide a full characterization of their mechanical behaviors. Additionally, it is still unclear if the TPMS scaffolds possess the similar anisotropic behaviors as the natural bones. The aim of the present study was to analyze the anisotropic elastic behaviors of TPMS based scaffolds using the numerical homogenization method and the analytical analysis approach. Five widely-used TPMS scaffold topologies (Diamond, Gyroid, Fischer-Koch S, Schwarz P and F-RD) were investigated. The independent elastic constants were determined from the analytical analysis and then, the values for these independent constants were determined using the finite element (FE) unit cell models of the scaffolds combined with the periodic boundary condition. The analytical analysis revealed that the Diamond, Gyroid and Fischer-Koch S topologies are threefold rotational symmetric and consequently have seven independent elastic constants. The Schwarz P and F-RD topologies are cubic symmetric and have three independent elastic constants. The FE analysis showed that the Diamond, Gyroid and Fischer-Koch S based scaffolds have only three non-zero independent elastic constants, implying the cubic symmetric property of these scaffolds. All the independent elastic constants decreased quadratically with the increase of scaffold porosity. The absolute difference between the Zener anisotropic factor and one increased the most for the Gyroid based scaffold, while the value for the Fischer-Koch S based scaffold increased the least. The present study revealed that all the five TPMS scaffolds possess cubic symmetry, limiting their anisotropic behaviors. The information on the Zener anisotropic factor and the relationship between the scaffold elastic constants and the porosity can facilitate the selection and design of scaffolds in biomedicine and relevant fields.

Giant Thermal Expansion in 2D and 3D Cellular Materials.

When temperature increases, the volume of an object changes. This property was quantified as the coefficient of thermal expansion only a few hundred years ago. Part of the reason is that the change of volume due to the variation of temperature is in general extremely small and imperceptible. Here, abnormal giant linear thermal expansions in different types of two-ingredient microstructured hierarchical and self-similar cellular materials are reported. The cellular materials can be 2D or 3D, and isotropic or anisotropic, with a positive or negative thermal expansion due to the convex or/and concave shape in their representative volume elements respectively. The magnitude of the thermal expansion coefficient can be several times larger than the highest value reported in the literature. This study suggests an innovative approach to develop temperature-sensitive functional materials and devices.

Simultaneously improving the mechanical and electrical properties of poly(vinyl alcohol) composites by high-quality graphitic nanoribbons.

Although carbon nanotubes (CNTs) have shown great potential for enhancing the performance of polymer matrices, their reinforcement role still needs to be further improved. Here we implement a structural modification of multi-walled CNTs (MWCNTs) to fully utilize their fascinating mechanical and electrical properties via longitudinal splitting of MWCNTs into graphitic nanoribbons (GNRs). This nanofiller design strategy is advantageous for surface functionalization, strong interface adhesion as well as boosting the interfacial contact area without losing the intrinsic graphitic structure. The obtained GNRs have planar geometry, quasi-1D structure and high-quality crystallinity, which outperforms their tubular counterparts, delivering a superior load-bearing efficiency and conductive network for realizing a synchronous improvement of the mechanical and electrical properties of a PVA-based composite. Compared to PVA/CNTs, the tensile strength, Young's modulus and electrical conductivity of the PVA/GNR composite at a filling concentration of 3.6 vol.% approach 119.1 MPa, 5.3 GPa and 2.4 × 10-4 S m-1, with increases of 17%, 32.5% and 5.9 folds, respectively. The correlated mechanics is further rationalized by finite element analysis, the generalized shear-lag theory and the fracture mechanisms.