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Confocal image showing actin cytoskeletal structure stained by rhodamine phalloidin in red and nucleus stained by DAPI in blue (upper right corner). The actin cortex was stained at the edge of the cell. FE model of a myoblast was built based on the confocal images. The blue circle indicated where the proximal end node of an apical stress fiber was anchored to the nearest node on the nucleus surface. The red circles indicated where the rest nodes of an apical stress fiber were anchored to the nearest nodes in the cytoplasm. The black circle indicated an end node of a basal stress fiber being anchored to the bottom of the cell model as a focal adhesion
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Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myobl...
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Actin-myosin filament bundles (stress fibers) are critical for tension generation and cell shape, but their mechanical properties are difficult to access. Here we propose a novel approach to probe individual peripheral stress fibers in living cells through a microsurgically generated opening in the cytoplasm. By applying large deformations with a s...
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Aims
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Citations
... These finite element models provide a valuable mean to thoroughly investigate the mechanical response of the cell nucleus, with a particular focus on the critical role played by the nuclear lamina. (Hobson and Stephens 2020) However, both the combined continuous and discrete model and the multi-structure continuous model have their limitations (Cao et al. 2016;Deveraux et al. 2017;Heo et al. 2020;Hobson et al. 2020;Khunsaraki et al. 2020a;Liu et al. 2019;Mukherjee et al. 2020;Wei et al. 2016;Yao et al. 2016). These models are more intricate and lack the simplicity of singular property models when examining specific characteristics. ...
We have developed a finite element model to simulate the penetration of nanoneedles into the cellular nucleus. It is found that the nuclear lamina, the primary supporting structure of the nuclear membrane, plays a crucial role in maintaining the integrity of the nuclear envelope and enhancing stress concentration in the nuclear membrane. Notably, nuclear lamina A exhibits a more pronounced effect compared to nuclear lamina B. Subsequently, we further conducted experiments by controlling the time of osteopontin (OPN) treatment to modify the nuclear lamina density, and the results showed that an increase in nuclear lamina density enhances the probability of nanoneedle penetration into the nuclear membrane. Through employing both simulation and experimental techniques, we have gathered compelling evidence indicating that an augmented density of nuclear lamina A can enhance the penetration of nanoneedles into the nuclear membrane.
... The results presented by Yao et al. showed that brief exposure to a relatively low dosage of oxidative stress could enhance the stress fiber density in cells (in this case, in myoblasts). The opposite effect was noticed as a result of chronic exposure and a high dosage of oxidative stress, which led to a significant decrease in the stress fiber density, a reaction which could suppress the stress fiber density in cells [22][23][24]. Moreover, the oxidative-stress-mediated activation of protein tyrosine kinases could also impair adherent junctions, which suggests a loss in endothelial barrier integrity [25]. ...
The term “nanosilica” refers to materials containing ultrafine particles. They have gained a rapid increase in popularity in a variety of applications and in numerous aspects of human life. Due to their unique physicochemical properties, SiO2 nanoparticles have attracted significant attention in the field of biomedicine. This study aimed to elucidate the mechanism underlying the cellular response to stress which is induced by the exposure of cells to both biogenic and pyrogenic silica nanoparticles and which may lead to their death. Both TEM and fluorescence microscopy investigations confirmed molecular changes in cells after treatment with silica nanoparticles. The cytotoxic activity of the compounds and intracellular RNS were determined in relation to HMEC-1 cells using the fluorimetric method. Apoptosis was quantified by microscopic assessment and by flow cytometry. Furthermore, the impact of nanosilica on cell migration and cell cycle arrest were determined. The obtained results compared the biological effects of mesoporous silica nanoparticles extracted from Urtica dioica L. and pyrogenic material and indicated that both types of NPs have an impact on RNS production causing apoptosis, necrosis, and autophagy. Although mesoporous silica nanoparticles did not cause cell cycle arrest, at the concentration of 50 μg/mL and higher they could disturb redox balance and stimulate cell migration.
... 51 This factor may affect the organization of intercellular connections (AJs, TJs) and the cytoskeleton, including actin filaments. 52 In the case of basal-like breast cancer tissue, the high level of FHOD1 was also presented. 32 Clinical trials show that an increase in mortality in patients with oncological diseases is often associated with the formation of metastases. 4 The actin network is involved in this process, while its dynamic is determined by the proteins accompanying microfilaments like formin. ...
Purpose
Metastasis remains a serious clinical problem in which epithelial-to-mesenchymal transition is strictly involved. The change of cell phenotype is closely related to the dynamics of the cytoskeleton. Regarding the great interest in microfilaments, the manipulation of ABPs (actin-binding proteins) appears to be an interesting treatment strategy.
Material
The research material was the highly aggressive A549 cells with FHOD1 (F FH1/FH2 domain-containing protein 1) downregulation. The metastatic potential of the cells and the sensitivity to treatment with alkaloids (piperlongumine, sanguinarine) were analyzed.
Results
In comparison to A549 cells with naïve expression of FHOD1, those after manipulation were characterized by a reduced migratory potential. The obtained results were associated with microfilaments and vimentin reorganization induced by the manipulation of FHOD1 together with alkaloids treatment. The result was also an increase in the percentage of late apoptotic cells.
Conclusion
Downregulation of FHOD1 induced reorganization of microfilament network followed by the reduction in the metastatic potential of the A549 cells, as well as their sensitization to selected compounds. The presented results and the analysis of clinical data indicate the possibility of transferring research from the basic level to in vivo models in the context of manipulation of ABPs as a new therapeutic target in oncology.
... OS arises following an imbalance between pro-oxidants and antioxidants, which impair intracellular homeostasis. OS causes damage to the cytoskeletal ultrastructure in normal cells [22,23], pre-and post-implantation embryos, in which their subsequent 4 th International Conference on Pharmacy and Pharmaceutical Science (ICPPS) 2019 81 development could be at stake [24,25]. Cigarette smoke, with its major content, consist of the alkaloid nicotine (Nic), contains pro-oxidants that may raise ROS. ...
Objective: This study aimed to determine the effects of the tocotrienol-rich fraction (TRF) on the regulations of phosphoinositide 3-kinases (PI3K)/Aktpathways related genes in preimplantation embryos induced by nicotine (Nic).Methods: Twenty-four female BALB/c mice were divided into four groups with Nic and TRF supplementation for 7 consecutive days. Animalswere superovulated before mating with fertile males. Plasma malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase weredetermined and analyzed accordingly. Embryos with two and eight blastomeres were assessed for gene expression analysis.Results: The levels of endogenous antioxidative enzymes for the group with TRF intervention and TRF only group showed no significant changes whencompared to the control group. The level of oxidative stress (OS) biomarkers was also significantly decreased when compared to the Nic-induced group.At 2-cell stage, Pten gene was significantly upregulated while Akt1, GSK3β, and Mapk1 were significantly downregulated almost similar to the baseline(control) in the Nic-induced mice. Intervention with TRF resulted in a significant downregulated of Pten gene followed by a significant upregulationof other genes. The same pattern was shown at the 8-cell stage.Conclusion: This showed that TRF evidently has OS protection capacity and it could be through modulating the PI3K/Akt signaling pathway.
... In computational modelling of single cell mechanics, the assumption of homogenous mechanical properties for the entire cell has been a strong simplification particularly for cells with focal adhesions where stress fibre presents critical inhomogeneity. Hybrid computational cell models [37,38,39] with a restricted number of tensegrity elements to represent the mechanical contribution of stress fibres have remained limited in their capabilities to capture real cellular behaviour. One of the main shortcomings of continuum based models is the lack All rights reserved. ...
Existing in silico models for single cells feature limited representations of cytoskeletal structures that present inhomogeneities in the cytoplasm and contribute substantially to the mechanical behaviour of the cell. Considering these microstructural inhomogeneities is expected to provide more realistic predictions of cellular and subcellular mechanics. Here, we propose a micromechanical hierarchical approach to capture the contribution of actin stress fibres to the mechanical behaviour of a single cell when exposed to substrate stretch. For a cell-specific geometry of a fibroblast with membrane, cytoplasm and nucleus obtained from confocal micrographs, the Mori-Tanaka homogenization method was employed to account for cytoplasmic inhomogeneities and constitutive contribution of actin stress fibres. The homogenization was implemented in finite element models of the fibroblast attached to a planar substrate with 124 focal adhesions. With these models, the strains in cell membrane, cytoplasm and nucleus due to uniaxial substrate stretch of 1.1 were assessed for different stress fibre volume fractions in the cytoplasm of up to 20% and different elastic modulus of the substrate. A considerable decrease of the peak strain with increasing stress fibre content was observed in cytoplasm and nucleus but not the cell membrane, whereas peak strain increased in cytoplasm, nucleus and membrane for increasing elastic modulus of the substrate. With the potential for extension, the developed method and models can contribute to more realistic in silico models of cellular mechanics.
... Like many intracellular macro and microstructures, actin proteins are also affected by oxidative stress and change their structures. 32 Lu and his colleagues have shown that smoking results in endothelial damage through increased oxidative stress in the lungs and impaired F-actin structure in endothelial cells in rats. 33 Simoneau et al. have shown that increased oxidative stress leads to actin fragmentation, impaired endothelial cell layer, and increased endothelial permeability. ...
Vulpinic acid, a lichen compound, has been shown to have many beneficial effects and its medicinal value increases day by day. As in atherosclerosis, endothelial damage is the basis of many diseases. The aim of this study is to investigate the effects of vulpinic acid against oxidative stress damage induced by hydrogen peroxide (H2O2) in endothelial cells. In order to find the IC50 of H2O2 and the protective dose of vulpinic acid, methyl thiazolyldiphenyl tetrazolium bromide (MTT) assays were performed. The amount of reactive oxygen species (ROS) induced by H2O2 and the protective effects of vulpinic acid against ROS were examined by fluorometric DCF-DA kit. The effects of H2O2 and vulpinic acid on actin filaments were determined by tetramethyl rhodamine (TRITC)-phalloidin fluorescence staining. Expression of Tie2 proteins was immunocytochemically analyzed in H2O2- and vulpinic acid-treated cells. After 24 h, the IC50 was found to be 215 μM in HUVECs treated with H2O2. The most effective dose of vulpinic acid against H2O2-associated damage was found to be 15 μM. Vulpinic acid pretreatment was shown to reduce H2O2-induced ROS production significantly ( p < 0.05). It was shown that 215 μM of H2O2 caused actin fragmentation, cell shrinkage, and decrease in actin florescence intensity while vulpinic acid protected the cells from these damages. It was found that Tie2 immunoreactivity was decreased in H2O2-treated groups and vulpinic acid pretreatment reduced the expression of this protein. In conclusion, vulpinic acid decreases H2O2-induced oxidative stress and oxidative stress-related damages in HUVECs. It may be drug candidate in the therapy of atherosclerosis.
... Human glial cells [85] Downregulation of actin polymerization-associated genes Aging Human myoblasts [86,87] Increased actin depolymerization and decreased in cell stiffness ...
The organization of actin filaments into a wide range of subcellular structures is a defining feature of cell shape and dynamics, important for tissue development and homeostasis. Nervous system function requires morphological and functional plasticity of neurons and glial cells, which is largely determined by the dynamic reorganization of the actin cytoskeleton in response to intrinsic and extracellular signals. Oligodendrocytes are specialized glia that extend multiple actin-based protrusions to form the multilayered myelin membrane that spirally wraps around axons, increasing conduction speed and promoting long-term axonal integrity. Myelination is a remarkable biological paradigm in development, and maintenance of myelin is essential for a healthy adult nervous system. In this review, we discuss how structure and dynamics of the actin cytoskeleton is a defining feature of myelinating oligodendrocytes’ biology and function. We also review “old and new” concepts to reflect on the potential role of the cytoskeleton in balancing life and death of myelin membranes and oligodendrocytes in the aging central nervous system.
... Actin filaments, being most abundant among all cytoskeletal constituents, make the largest contribution to the mechanical properties of cell. Cells often modify their actin filamentous network in response to biochemical changes 14 . Recent publications have revealed that the biogenesis and trafficking of autophagy depend on the activities of several cytoskeletal components including actin assembly factors, signaling proteins and microtubule or actin-based motors 15,16 . ...
The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.
... Oxidative stress (OS) arises when there is an imbalance between pro-oxidants and antioxidants, which consequently impairs intracellular homeostasis. The damage from oxidative stress can include damage to cytoskeletal ultrastructures in normal cells [14,15], in pre-and post-implantation embryos, where it could affect their subsequent development [16][17][18][19]. It could also affect intrauterine foetal growth [19,20], pregnancy outcome and survival of the neonates in mice [21,22]. ...
This review summarizes the impact of tocotrienols (TCTs) as antioxidants in minimizing
oxidative stress (OS), particularly in embryos exposed to OS causing agents. OS level is
increased, for example, by nicotine, a major alkaloid content in cigarette, which is also a source
of exogenous reactive oxygen species (ROS). Increased nicotine-induced OS increases cell
stress response, which is a common trigger leading to embryonic cell death. Having more
profound anti-oxidative stress effects than its counterpart tocopherol, TCTs improve blastocyst
implantation, foetal growth, pregnancy outcome and survival of the neonates affected by
nicotine. In reversing cell developmental arrest caused by nicotine-induced OS, TCTs enhances
PDK-1 expression in the P13K/Akt pathway and permit embryonic development beyond the 4-
cell stage with the production of more morulae. At the cytoskeletal level, TCTs increase the
number of nicotine-induced apoptotic cells, through caspase 8 activation in the mitochondria.
TCTs facilitate rough endoplasmic reticulum (rER) stress-mediated apoptosis and autophagy,
resulting from nicotine-induced OS. Reduced vesicular population in TCT supplemented
oocytes on the other hand may suggest reduced secretion of apoptotic cell bodies thus probably
minimizing vesicular apoptosis during oocyte maturation. Further extensive research is
required to develop TCTs as a tool in specific therapeutic approaches to overcome the
detrimental effects of OS.
... Such changes in cytoskeletal mechanobiology and cell mechanics could be responsible for the strengthening effects of the mild cyclic compressive stimulation observed in this study. Stiffer actin stress fibers and actin cortex could decrease tensile strain in the cell plasma membrane when cells are subjected to compression (Yao et al., 2016). The plasma membrane of cells under static loading possibly sustain less tensile strain with stiffer cytoskeleton induced by the mild cyclic mechanical stimulation. ...
