Unique Role of Vimentin Networks in Compression Stiffening of Cells and Protection of Nuclei from Compressive Stress.

In this work, we investigate whether stiffening in compression is a feature of single cells and whether the intracellular polymer networks that comprise the cytoskeleton (all of which stiffen with increasing shear strain) stiffen or soften when subjected to compressive strains. We find that individual cells, such as fibroblasts, stiffen at physiologically relevant compressive strains, but genetic ablation of vimentin diminishes this effect. Further, we show that unlike networks of purified F-actin or microtubules, which soften in compression, vimentin intermediate filament networks stiffen in both compression and extension, and we present a theoretical model to explain this response based on the flexibility of vimentin filaments and their surface charge, which resists volume changes of the network under compression. These results provide a new framework by which to understand the mechanical responses of cells and point to a central role of intermediate filaments in response to compression.

Ultrafast Time-Resolved Pump-Probe Investigation of Nanosecond Extreme Ultraviolet-Light-Induced Damage Dynamics on B4C/Ru Nano-Bilayer Film.

An ultrafast time-resolved pump-probe setup with both high temporal and spatial resolution is developed to investigate the transient interaction between a nanosecond extreme ultraviolet (EUV) pulse and matter. By using a delayed femtosecond probe pulse, the pattern evolution of surface modification induced by an EUV pump at a wavelength of 13.5 nm can be imaged at different delay times, which provides deep insight into the EUV-induced damage dynamics and damage mechanisms. As a demonstration, single-shot EUV damage on a B4C(6.0 nm)/Ru(30.4 nm)/D263 nano-bilayer optical film is studied using this pump-probe method. A recoverable phenomenon is found during the evolution process of the dome-shaped damage region. This is explained by the elastic and plastic deformations resulting from the huge compressive stress difference at the Ru-substrate interface with the help of simulations on the thermal effects and mechanical responses. This damage mechanism is further proven by the complementary experiments at a higher EUV fluence at 13.5 nm.

Xenon Ion Implantation Induced Surface Compressive Stress for Preventing Dendrite Penetration in Solid-State Electrolytes.

Solid-state electrolytes (SSEs) have been thrust into the limelight for the revival of energy-dense lithium metal batteries, but still face the challenge of failure caused by the dendrite penetration. Mounting evidence indicates that dendrite penetration is related to the mechanical failure in SSEs, which calls for mechanical engineering to tackle this problem. This work reports a proof of concept that ion implantation induced surface compressive stress enables resistance in the dendrite penetration. A deterministic sequential multiple ion energies implantation is used to generate compressive stress, with implanted Xe ions distributed in a range of 160-600 Å from the surface. The symmetric lithium cells show that pellets with an implantation dose of 1013 Xe cm-2 exhibit stable stripping/plating cycles and extended lifespan, while a lower dose of 1012 Xe cm-2 cannot create sufficient stress to prevent dendrite penetration, and an excessive dose of 1014 Xe cm-2 leads to structural destruction and a decrease in stress. This improved performance is attributed to the induced surface compressive stress balanced over crystal grains, which is confirmed by grazing incidence diffraction techniques. The author's efforts demonstrate the usefulness of surface compressive stress to suppress dendrite penetration, offering more insight into rational stress-strain engineering as opposed to empirical optimization.

Pressure Loading Induces DNA Damage in Human Hepatocyte Line L02 Cells via the ERK1/2-Dicer Signaling Pathway.

Alteration of liver tissue mechanical microenvironment is proven to be a key factor for causing hepatocyte injury and even triggering the occurrence of hepatocellular carcinoma; however, the underlying mechanisms involved are not fully understood. In this study, using a customized, pressure-loading device, we assess the effect of pressure loading on DNA damage in human hepatocytes. We show that pressure loading leads to DNA damage and S-phase arresting in the cell cycle, and activates the DNA damage response in hepatocytes. Meanwhile, pressure loading upregulates Dicer expression, and its silencing exacerbates pressure-induced DNA damage. Moreover, pressure loading also activates ERK1/2 signaling molecules. Blockage of ERK1/2 signaling inhibits pressure-upregulated Dicer expression and exacerbates DNA damage by suppressing DNA damage response in hepatocytes. Our findings demonstrate that compressive stress loading induces hepatocyte DNA damage through the ERK1/2-Dicer signaling pathway, which provides evidence for a better understanding of the link between the altered mechanical environment and liver diseases.

Self-Healing of Nanoporous Gold Under Ambient Conditions.

Failure of a material is an irreversible process since the material loses its original characteristics and properties. The catastrophic brittle failure under tensile stress of nanoporous gold (np-Au) with a bicontinuous open-cell structure makes impossible otherwise attractive applications. Here, we first demonstrate a self-healing process in tensile-fractured np-Au to overcome the limit of fragility via mechanically assisted cold-welding under ambient conditions. The self-healing ability of np-Au in terms of mechanical properties shows strength recovery up to 64.4% and fully recovered elastic modulus compared with initial tensile properties. Topological parameters obtained by three-dimensional reconstruction of self-healed np-Au clarify the strength, elastic modulus, and strain distribution. The self-healing process in np-Au is attributed to surface diffusion expedited by local compressive stress in the ultrasmall dimension of ligaments formed by ductile failures of individual ligaments.

Development of an Aged Full-Thickness Skin Model Using Flexible Skin-on-a-Chip Subjected to Mechanical Stimulus Reflecting the Circadian Rhythm.

The skin is subject to both intrinsic aging caused by metabolic processes in the body and extrinsic aging caused by exposure to environmental factors. Intrinsic aging is an important obstacle to in vitro experimentation as its long-term progression is difficult to replicate. Here, we accelerated aging of a full-thickness skin equivalent by applying periodic mechanical stimulation, replicating the circadian rhythm for 28 days. This aging skin model was developed by culturing a full-thickness, three-dimensional skin equivalent with human fibroblasts and keratinocytes to produce flexible skin-on-a-chip. Accelerated aging associated with periodic compressive stress was evidenced by reductions in the epidermal layer thickness, contraction rate, and secretion of Myb. Increases in ß-galactosidase gene expression and secretion of reactive oxygen species and transforming growth factor-ß1 were also observed. This in vitro aging skin model is expected to greatly accelerate drug development for skin diseases and cosmetics that cannot be tested on animals.

A Simulation Case Study of Knee Joint Compressive Stress during the Stance Phase in Severe Knee Osteoarthritis Using Finite Element Method.

Background and Objectives: Medial knee osteoarthritis is known to increase the mechanical load on the medial compartment of the knee joint during walking; however, it is not visually understood how much the mechanical load increases nor where in the medial compartment of the knee joint that load is focused. Therefore, we conducted a simulation study to determine the location and amount of the mechanical load in the medial compartment of the knee joint during the stance phase. Materials and Methods: Subject was a patient with right medial knee osteoarthritis. Computed tomography imaging and gait analysis were performed on subject. The CT image of the right knee was calculated using finite element analysis software. Since this software can set the flexion angle arbitrarily while maintaining the nonuniform material properties of the bone region, the model is constructed by matching the knee joint extension image obtained by CT to the loading response phase of gait analysis. The data of muscle exertion tension and vertical ground reaction force were inserted into the knee joint model created from the computed tomography-based finite element method, and the knee joint compressive stress was calculated. Results: With regard to compressive stress, the tibia showed high stress at 4.10 to 5.36 N/mm2. The femur showed high stress at 4.00 to 6.48 N/mm2. The joint compressive stress on the medial compartment of the knee joint was found to concentrate on the edge of the medial tibial condyle in the medial knee osteoarthritis subject. Conclusions: The measurement method of knee joint compressive stress by computed tomography-based finite element method can visually be a reliable method of measuring joint compressive stress in the medial knee osteoarthritis. This reflects the clinical findings because concentration of stress on the medial knee joint was observed at the medial osteophyte.

Breaking of buckled microtubules is mediated by kinesins.

Microtubule is the most rigid component of eukaryotic cytoskeleton that plays pivotal roles in many important cellular events. Microtubules are known to undergo bending or buckling in cells which often results in breaking of this cytoskeletal protein filament. Various cellular events such as cell migration, chromosome segregation, etc. are dependent on the buckling induced breaking of microtubules. However, the reason behind the breaking of buckled microtubules in cell has remained obscure yet. In this work, we have demonstrated breaking of microtubules on a 2D elastic medium by applying compressive stress. The applied compressive stress caused buckling of the microtubules which ultimately resulted in their breaking. We show that breaking of the buckled microtubules cannot be accounted for by considering the changes in curvature of the microtubules due to mechanical deformation. Our results confirm that, it is the interaction of kinesin, a microtubule-associated motor protein, with microtubules which plays the key role in breaking of the buckled microtubules on the 2D elastic medium. The breaking of buckled microtubules is ascribed to decrease in rigidity of microtubules upon interaction with kinesins. This work for the first time confirms the involvement of a microtubule-associated motor protein in breaking of microtubules under compressive stress, which will help further clarify the mechanism of breaking of buckled microtubules in cells and its significance in the cellular events.

The role of sphingosine-1-phosphate signaling pathway in cementocyte mechanotransduction.

Iatrogenic external root resorption can become a serious pathological condition with clinical tooth movement. Little is known regarding how cementum responds to mechanical loading in contrast to bone, especially under compressive stress. In the field of bone biology, several studies have established the contribution of sphingosine-1-phosphate (S1P) signaling in bone remodeling, mechanical transduction and homeostasis. As osteocytes and cementocytes share similar morphological and functional characteristics, this study aimed to investigate the mechanotransduction ability of cementocytes and to explore the contribution of S1P signaling under compressive stress induced mechanotransduction. We found that compressive stress inhibited major S1P signaling and promoted the expression of anabolic factors in IDG-CM6 cells, a novel immortalized murine cementocyte cell line. By inhibiting S1P signaling, we verified that S1P signaling played a vital role in regulating the expression of the mechanotransduction factors prostaglandin E2 (PGE2) and ß-catenin, as well as factors responsible for cementogenesis and cementoclastogenesis in IDG-CM6 cells. These results support the hypothesis that cementocytes act as key mechanically responsive cells in cementum, responding to compressive stress and directing local cementum metabolism.

Compressive stress-induced autophagy promotes invasion of HeLa cells by facilitating protein turnover in vitro.

Metastasis remains the primary cause of cancer mortality. Throughout the process of metastasis, cancer cells experience mechanical forces, which may turn out to be the key towards their migratory, homeostatic and survival characteristics. However, the influence of compressive stress on the underlying mechanism of cancer cell adaptation during metastasis has remained grossly unexplored. In this study, we have investigated whether compressive force induces autophagy in HeLa cells with potential implications in cellular invasiveness. To this end, we have adopted a simple strategy to create the mechanically-compressed tumor microenvironment, in vitro, by applying appropriate compression to agarose-scaffolded HeLa cell-encapsulated alginate beads. Our findings confirm that compression upregulates autophagy, which promotes paxillin turnover and active MMP-2 secretion, leading to enhanced migration of HeLa cells. We further show that autophagy induction by compression is affected by the phosphorylation of p38 MAPKs, a process that is mediated by intact membrane lipid rafts. Identifying the role of such mechanically triggered cellular responses, guiding crucial processes like cell migration, may lead to better understanding of the mechanobiological aspects of metastatic cancer and unveil potential therapeutic targets.

SCWISh network is essential for survival under mechanical pressure.

Cells that proliferate within a confined environment build up mechanical compressive stress. For example, mechanical pressure emerges in the naturally space-limited tumor environment. However, little is known about how cells sense and respond to mechanical compression. We developed microfluidic bioreactors to enable the investigation of the effects of compressive stress on the growth of the genetically tractable model organism Saccharomyces cerevisiae We used this system to determine that compressive stress is partly sensed through a module consisting of the mucin Msb2 and the cell wall protein Sho1, which act together as a sensor module in one of the two major osmosensing pathways in budding yeast. This signal is transmitted via the MAPKKK kinase Ste11. Thus, we term this mechanosensitive pathway the "SMuSh" pathway, for Ste11 through Mucin/Sho1 pathway. The SMuSh pathway delays cells in the G1 phase of the cell cycle and improves cell survival in response to growth-induced pressure. We also found that the cell wall integrity (CWI) pathway contributes to the response to mechanical compressive stress. These latter results are confirmed in complimentary experiments in Mishra et al. [Mishra R, et al. (2017) Proc Natl Acad Sci USA, 10.1073/pnas.1709079114]. When both the SMuSh and the CWI pathways are deleted, cells fail to adapt to compressive stress, and all cells lyse at relatively low pressure when grown in confinement. Thus, we define a network that is essential for cell survival during growth under pressure. We term this mechanosensory system the SCWISh (survival through the CWI and SMuSh) network.

A New Approach to Explore the Surface Profile of Clay Soil Using White Light Interferometry.

In order to have a better understanding of the real contact area of granular materials, the white light interference method is applied to explore the real surface morphology of clay soils under high stress. Analysis of the surface profile indicates that there exists a support point height z0 with the highest distribution frequency. A concept of a real contact region (from z0 to z0 + d90; d90 represents the particle size corresponding to 90% of the volume fraction) is proposed by combining a surface profile with the particle size distribution of clay soil. It was found that under the compressive stress of 106 MPa-529 MPa, the actual contact area ratio of clay soil varies between 0.375 and 0.431. This demonstrates an increasing trend with the rise of stress. On the contrary, the apparent porosity decreases with an increasing stress, varying between 0.554 and 0.525. In addition, as the compressive stress increases, the cumulative frequency of apparent profile height (from z0 - d90 to z0 + d90) has a concentrated tendency with a limited value of 0.9.

Comparison of failure loads and compressive stress in Press on metal and Press on Y-TZP copings.

OBJECTIVE: The aim of the study was to assess the failure loads and compressive stresses among bilayered press on Y-TZP (POZ) and press on metal (POM) crowns with different core-veneer thickness. METHODS: Thirty metal and Y-TZP copings were fabricated using CAD-CAM technology with specified thickness. All copings were veneered with ceramic materials using hot pressing technique, with 2mm and 2.5mm thickness. The different coping veneer thickness of crowns resulted in six study groups, including, POM: Coping/ veneer thickness of 0.7/2mm (Gp1), 0.7/2.5mm (Gp 2) and 1mm/2mm (Gp 3)-POZ: 0.7/2mm (Gp A), 0.7/2.5mm (Gp B) and 1mm/2mm (Gp C). Crowns were cemented to a standard implant analog and failure loads (FL) and compressive stress (CS) was ascertained by controlled load application in a universal testing machine. Data was analysed using ANOVA and multiple comparisons test. RESULTS: The maximum FL were observed in the POM specimens with a C/V ratio of 1/2 (Group 3-1880.67± 256.78 N), however the lowest FL were exhibited by POZ crowns with 1/2 C/V ratio (Group C-611.89± 72.79 N). Mean FL and CS were significantly higher in POM compared to POZ crowns in respective groups. Increasing the coping-veneer thickness increased FL and CS among POM crowns. Increasing veneer and decreasing coping thickness improved FL and CS among POZ crowns. CONCLUSIONS: Press on metal specimen showed higher resistance to fracture than Press on Y-TZP specimens. Improved failure loads were observed in thin coping and thick veneers among Press on Y-TZP crowns.

Effect of cyclic uniaxial compressive stress on human dental pulp cells in vitro.

PURPOSE: Teeth are exposed to various forces during functional and parafunctional movements. These processes inevitably affect the dental pulp, and the mechanism of these influences has been the subject of many previous studies using different apparatuses and obtaining different results. In this study, we aimed to investigate the effects of compressive stress on the proliferation and differentiation of human dental pulp cells (hDPCs). MATERIALS AND METHODS: A four-point bending strain system was adopted to apply low-density cyclic uniaxial compressive stress (2000 microstrain, 0.5 Hz) to hDPCs for 1.5, 3, 6, 12, and 24 h. The cell cycle progression and mRNA expression of differentiation-related genes (BMP2, ALP, DMP1, DSPP, COL I) were then examined to investigate the proliferation and differentiation of hDPCs. RESULTS: The results showed that cyclic compressive stress changed the morphology of hDPCs after 12 and 24 h of mechanical loading; cell cycle progression was promoted, especially in the 24-h group (p < 0.05). The expression of BMP2 was significantly upregulated after 3 and 6 h of mechanical loading but declined in the 12- and 24-h groups, whereas the expression levels of DMP1 and DSPP were significantly upregulated in the 12- and 24-h loading groups (p < 0.05). CONCLUSIONS: Dental pulp cells were sensitive to compressive stress, especially after 12 and 24 h of applied force. Proliferation and odontogenic differentiation were significantly promoted in this in vitro model.

Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner. Moreover, the mRNA level of Scinderin (Scin) considerably increased. We established lentivirus-SCIN(GV144-SCIN) to transfect hBMSCs, which were treated with different Ccs levels (0.25 Hz*5 cm, 0.5 Hz*5 cm, and 1 Hz*10 cm); the result showed that overexpression of Scin upregulated osteogenesis and osteoclastogenesis. By contrast, expression of chondrocyte-specific genes, including ACAN, COL-2A, and Sox9, decreased. Further molecular investigation demonstrated that Scin promoted osteogenesis and osteoclastogenesis through activation of the p-Smad1/5/8, NF-κB, and MAPK P38 signaling pathways, as well as stimulated the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Moreover, Scin-induced osteogenesis outweighed osteoclastogenesis in defective femur in vivo. The results of the analysis of Micro-CT confirmed these findings. Overall, Ccs influenced the development of DDH by promoting osteogenesis and cartilage degradation. In addition, Scin played a vital role in the development of DDH.

Plateau-Rayleigh Crystal Growth of Nanowire Heterostructures: Strain-Modified Surface Chemistry and Morphological Control in One, Two, and Three Dimensions.

One-dimensional (1D) structures offer unique opportunities for materials synthesis since crystal phases and morphologies that are difficult or impossible to achieve in macroscopic crystals can be synthesized as 1D nanowires (NWs). Recently, we demonstrated one such phenomenon unique to growth on a 1D substrate, termed Plateau-Rayleigh (P-R) crystal growth, where periodic shells develop along a NW core to form diameter-modulated NW homostructures with tunable morphologies. Here we report a novel extension of the P-R crystal growth concept with the synthesis of heterostructures in which Ge (Si) is deposited on Si (Ge) 1D cores to generate complex NW morphologies in 1, 2, or 3D. Depositing Ge on 50 nm Si cores with a constant GeH4 pressure yields a single set of periodic shells, while sequential variation of GeH4 pressure can yield multimodulated 1D NWs with two distinct sets of shell periodicities. P-R crystal growth on 30 nm cores also produces 2D loop structures, where Ge (Si) shells lie primarily on the outside (inside) of a highly curved Si (Ge) core. Systematic investigation of shell morphology as a function of growth time indicates that Ge shells grow in length along positive curvature Si cores faster than along straight Si cores by an order of magnitude. Short Ge deposition times reveal that shells develop on opposite sides of 50 and 100 nm Si cores to form straight 1D morphologies but that shells develop on the same side of 20 nm cores to produce 2D loop and 3D spring structures. These results suggest that strain mediates the formation of 2 and 3D morphologies by altering the NW's surface chemistry and that surface diffusion of heteroatoms on flexible freestanding 1D substrates can facilitate this strain-mediated mechanism.

First-principles quantum molecular dynamics study of Ti x Zr1-x N(111)/SiN y heterostructures and comparison with experimental results.

The heterostructures of five monolayers B1-Ti x Zr1-x N(111), x = 1.0, 0.6, 0.4 and 0.0 (where B1 is a NaCl-type structure) with one monolayer of a Si3N4-like Si2N3 interfacial layer were investigated by means of first-principles quantum molecular dynamics and a structure optimization procedure using the Quantum ESPRESSO code. Slabs consisting of stoichiometric TiN and ZrN and random, as well as segregated, B1-Ti x Zr1-x N(111) solutions were considered. The calculations of the B1-Ti x Zr1-x N solid solutions, as well as of the heterostructures, showed that the pseudo-binary TiN-ZrN system exhibits a miscibility gap. The segregated heterostructures in which Zr atoms surround the Si y N z interface were found to be the most stable. For the Zr-rich heterostructures, the total energy of the random solid solution was lower compared to that of the segregated one, whereas for the Ti-rich heterostructures the opposite tendency was observed. Hard and super hard Zr-Ti-Si-N coatings with thicknesses from 2.8 to 3.5 µm were obtained using a vacuum arc source with high frequency stimulation. The samples were annealed in a vacuum and in air at 1200 °C. Experimental investigations of Zr-Ti-N, Zr-Ti-Si-N and Ti-Si-N coatings with different Zr, Ti and Si concentrations were carried out for comparison with results obtained from Ti x Zr 1-x N(111)/SiN y systems. During annealing, the hardness of the best series samples was increased from (39.6 ± 1.4) to 53.6 GPa, which seemed to indicate that a spinodal segregation along grain interfaces was finished. A maximum hardness of 40.8 GPa before and 55 GPa after annealing in air at 500 °C was observed for coatings with a concentration of elements of Si≽ (7-8) at.%, Ti ≽ 22 at.% and Zr ⩽ 70 at.%.

Bacteria Colonies Modify Their Shear and Compressive Mechanical Properties in Response to Different Growth Substrates.

Bacteria build multicellular communities termed biofilms, which are often encased in a self-secreted extracellular matrix that gives the community mechanical strength and protection against harsh chemicals. How bacteria assemble distinct multicellular structures in response to different environmental conditions remains incompletely understood. Here, we investigated the connection between bacteria colony mechanics and the colony growth substrate by measuring the oscillatory shear and compressive rheology of bacteria colonies grown on agar substrates. We found that bacteria colonies modify their own mechanical properties in response to shear and uniaxial compression in a manner that depends on the concentration of agar in their growth substrate. These findings highlight that mechanical interactions between bacteria and their microenvironments are an important element in bacteria colony development, which can aid in developing strategies to disrupt or reduce biofilm growth.

Eggshell derived scaffold of hydroxyapatite-ammonium bicarbonate nano-composite: Bioactivity and cytotoxicity studies.

This work investigated the facile synthesis of porous scaffold eggshell derived hydroxylapatite (ESHAp) as a composite with ammonium bicarbonate (AMB) for potential biomaterial in tissue engineering application. The phase purity, composition, size, functional groups and morphology of the apatite were elucidated using high resolution transmission electron microscopy (HTEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR) and scanning electron microscopy (SEM). The results showed that hydroxylapatite (HAp) nanoparticles have round morphologies with average diameters between 20 nm and 80 nm, FT-IR analysis confirmed significant hydroxylapatite functional groups like carbonate, phosphate, and hydroxyl groups, while XRD analysis revealed a well crystalline monophasic HAp powder. The scaffold samples containing 10, 20, 25 and 30 % of AMB withstood a compressive stress up to 5, 20, 30 and 42 N/mm2 respectively which indicates that the compressive stress increased with the AMB content introduced as the pore forming agent. MTT assay performed using MG63 osteosarcoma cell lines showed that on comparing the sample of ESTHAp which contained 0 % AMB with other samples in the range of 0.01-1 mM, viability of above 85 % MG63 cells was achieved except for ESTHAp with 40 % AMB, which showed some level of toxicity. The cell adhesion studies of sintered ESTHAp porous scaffold with different weight percent of the pore forming agents using inverted microscopic images of MG 63 cells incubated with ESTHAp samples and treated with heat at 1000 °C appeared to be unstable in the media used with particle leaching observed, and no cells observed near to the samples.

The role and mechanism of compressive stress in tumor.

Recent research has revealed the important role of mechanical forces in the initiation and progression of tumors. The interplay between mechanical and biochemical cues affects the function and behavior of tumor cells during the development of solid tumors, especially their metastatic potential. The compression force generated by excessive cell proliferation and the tumor microenvironment widely regulates the progression of solid tumor disease. Tumor cells can sense alterations in compressive stress through diverse mechanosensitive components and adapt their mechanical characteristics accordingly to adapt to environmental changes. Here, we summarize the current role of compressive stress in regulating tumor behavior and its biophysical mechanism from the mechanobiological direction.