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Cells are in complicated mechanical and physical microenvironment in vivo. The former mainly includes flow shear, tension, compression or torsion, and the latter covers stiffness and topography of extracellular matrix, spatial location, volume constraint or osmotic pressure, featured with various types, patterns, and parameters of mechanical or physical loading. Cell biomechanics mainly focuses on the alteration of mechanical properties of cells and the mechanical remodeling of subcellular components, the cell development, growth, proliferation, differentiation, and apoptosis under distinct mechanical stimuli, and the cellular sensation, transmission, transduction, and responses to external forces. This review summarized the major progresses in cell biomechanics in 2021, including studies on cardiomyocytes, endothelial cells, osteoblasts, immune cells, cancer cells and stem cells, as well as the related new techniques.
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As one of the major branches in biomechanics, cellular and molecular biomechanics have made much progress in mechano-biological and mechano-chemical coupling in the past decades. Cells sense various in vivo mechanical stimuli, which initiate downstream signaling via mechanosensitive proteins to balance external forces. It is required to understand what mechanical features of distinct cells are and how external forces are transduced to biochemical signals. Multi-scale integration from cellular, subcellular, to molecular level in a cell promotes the understanding of mechanosensation, mechanotransmission, mechanotransduction, and mechanoepigenetics. In this review, the progress update in cellular and molecular biomechanics is provided and relevant scientific issues, methodological approaches, and potential applications are discussed.
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With the development of space life science, researches on ground-based microgravity simulation become more and more important for spaceflight to complement their limited missions. It is well known that bone marrow mesenchymal stem cells (BMSCs) are pluripotent, self-renewing cells with multi-lineage differentiation capacity on the ground, but their responses under microgravity and the underlying regulatory mechanisms are poorly understood. Ground-based microgravity simulation might affect cell proliferation, apoptosis and expression of surface molecules, and induce cytoskeletal reorganization, as well as alter the differentiation potential of BMSCs. In this review, how ground based microgravity simulation mediates BMSCs’ responses and its involved mechanisms are summarized to further understand the mechano-biological coupling in such process and provide theoretical references for space flight-induced pathophysiological alterations.
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Cell biology experiments in space are indispensable for investigating the effects of microgravity environment on living organisms. As an important technological means of supporting life science researche, space cell bioreactor may directly influence the data quality of space cell biology experiments and research level. To date, space cell bioreactor techniques are still under development, and lack of standard rationale. In this article, the technical progresses of space cell bioreactor were reviewed, by introducing the operational principle of several typical space cell bioreactors, analyzing the mode of culture medium supplying and character of fluid mechanics environment in space, as well as the relevant supporting techniques about the parametric controlling on temperature, dissolved oxygen and pH value and on-line microscopic imaging, so as to discuss the future perspective about space cell bioreactor techniques.
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Cells sense various in vivo mechanical stimuli, which initiate downstream signaling to mechanical forces. While a body of evidences is presented on the impact of limited mechanical regulators in past decades, the mechanisms how biomechanical responses globally affect cell function need to be addressed. Complexity and diversity of in vivo mechanical clues present distinct patterns of shear flow, tensile stretch, or mechanical compression with various parametric combination of its magnitude, duration, or frequency. Thus, it is required to understand, from the viewpoint of mechanobiology, what mechanical features of cells are, why mechanical properties are different among distinct cell types, and how forces are transduced to downstream biochemical signals. Meanwhile, those in vitro isolated mechanical stimuli are usually coupled together in vivo, suggesting that the different factors that are in effect individually could be canceled out or orchestrated with each other. Evidently, omics analysis, a powerful tool in the field of system biology, is advantageous to combine with mechanobiology and then to map the full-set of mechanically sensitive proteins and transcripts encoded by its genome. This new emerging field, namely mechanomics, makes it possible to elucidate the global responses under systematically-varied mechanical stimuli. This review discusses the current advances in the related fields of mechanomics and elaborates how cells sense external forces and activate the biological responses.
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Humans , Biomechanical Phenomena , Gene Expression Regulation , Mechanotransduction, Cellular , Models, Biological , Proteome , Genetics , Metabolism , Stress, Physiological , TranscriptomeABSTRACT
<p><b>OBJECTIVE</b>To study, at the cytological level, the basic concept of Chinese medicine that "the Kidney (Shen) controls the bone".</p><p><b>METHODS</b>Kaempferol was isolated form Rhizoma Drynariae (Gu Sui Bu, GSB) and at several concentrations was incubated with opossum kidney (OK) cells, osteoblasts (MC3T3 E1) and human fibroblasts (HF) at cell concentrations of 2×10(4)/mL. Opossum kidney cell-conditioned culture media with kaempferol at 70 nmol/L (70kaeOKM) and without kaempferol (0OKM) were used to stimulate MC3T3 E1 and HF proliferation. The bone morphological protein receptors I and II (BMPR I and II) in OK cells were identified by immune-fluorescence staining and Western blot analysis.</p><p><b>RESULTS</b>Kaempferol was found to increase OK cell growth (P<0.05), but alone did not promote MC3T3 E1 or HF cell proliferation. However, although OKM by itself increased MC3T3 E1 growth by 198% (P<0.01), the 70kaeOKM further increased the growth of these cells by an additional 127% (P<0.01). It indicates that the kidney cell generates a previously unknown osteoblast growth factor (OGF) and kaempferol increases kidney cell secretion of OGF. Neither of these media had any significant effect on HF growth. Kaempferol also was found to increase the level of the BMPR II in OK cells.</p><p><b>CONCLUSIONS</b>This lends strong support to the original idea that the Kidney has a significant influence over bone-formation, as suggested by some long-standing Chinese medical beliefs, kaempferol may also serve to stimulate kidney repair and indirectly stimulate bone formation.</p>
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Animals , Mice , 3T3 Cells , Cell Line , Culture Media, Conditioned , Intercellular Signaling Peptides and Proteins , Bodily Secretions , Kaempferols , Pharmacology , Kidney Tubules , Physiology , Bodily Secretions , Medicine, Chinese Traditional , Opossums , Osteoblasts , ChemistryABSTRACT
Culturing cells on planar substrate in vitro is a conventional cell biology method. However, each type of physiological tissues has its specific three-dimensional micro-structure, which provides various micro environment to regulate such biological processes as cell proliferation and differentiation. To date, a growing body of researches on the impacts of substrate micro-topography on cellular responses has been documented in the literature. It is found that micro-topograhical substrate can manipulate cell spreading, migrating, orientating, cytoskeleton remodeling, and stem cell differentiation, which are crucial to ex vivo tissue construction and surface modification of medical implanting materials. This review discusses the recent progresses of the effects of substrate micro-topography on cellular responses and the underlying mechanisms of mechano-biological coupling.
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Objective To elucidate the spreading dynamics of β2 integrin expressed human neutrophils (PMNs) on ICAM-1-immobilized substrate. Methods The fraction of PMN spreading on the substrate pre coated by 10, 20, or 100 μg/mL intercellular adhesive molecule-1 (ICAM-1) was quantified when that on 2% human serum albumin (HSA) immobilized or that on blank substrate was served as control. The site density of β2 integrin expressing on PMNs was determined using flow cytometry and the regulation of β2 integrin subunits was defined using the fraction of PMN spreading on 100 μg/mL ICAM-1 substrate by blocking CD11a or CD11b subunit of β2 integrin. Results PMN spreading was presented on ICAM-1-immobilized substrate but absent on 2% HSA-immobilized substrate, supporting the specificity of β2 integrin induced spreading. Time course of neutrophil spreading on ICAM-1 substrate was density dependent of both ICAM-1 and β2 integrin molecules. The fraction of PMN spreading was reduced significantly when the expression of CD11b subunit was blocked. Conclusions PMN spreading was mediated specifically by β2 integrin-ICAM-1 interactions and determined by the expression of β2 integrin and ICAM-1, in which CD11b subunit played a dominate role.
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Objective To investigate the specific roles of gap junction and ATP in mechanical stimulation induced calcium transfer in osteoblasts. Methods The isolated osteoblastic pattern without gap junctions was established by using the micropatterning method. Then fluid shear stress was applied on cells using the flow chamber to observe and analyze the characteristic parameters of calcium response. Results Multiple calcium response still occurred in osteoblastic pattern without gap junction, but the response time to the first responsive peak was much longer than that with gap junction. When the intracellular and extracellular calcium ions were removed, only 40% cells responded to the mechanical stimulation, with single peak and multiple peaks accounting for 50%, respectively. If ATP pathway was blocked, only 20% cells responded, most of which showed single peak. Conclusions ATP was the major pathway mediating intercellular calcium transfer, while the gap junction was not the necessary one.
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Selectin/ligand interaction plays an important role in such biological processes as inflammatory reaction, tumor metastasis, etc. External forces affect dissociation of receptor-ligand bonds. A novel approach, upon optical trap technique, was developed in this study to investigate the dissociation of P-selectin/PSGL-1 (P-Selectin Glycoprotein Ligand 1) bindings. Stiffness of optical trap was calibrated with laser power using a viscous drag method. While P-selectin and PSGL-1 molecules were functionally coated on surfaces of glass beads, respectively, the dissociation of interacting molecule bond was studied by measuring the rupture force distribution. It was found that most probable rupture force increased with loading rate at < 25 pN/s. These results complemented and validated the current theory at low loading rates.
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Humans , Membrane Glycoproteins , Chemistry , Optics and Photonics , Protein Binding , Protein Structure, TertiaryABSTRACT
The viscoelastic properties of hepatocellular carcinoma (HCC) cells were measured by means of micropipette aspiration technique. Further,the authors studied the changes in viscoelastic coefficients by treating with colchicine and cytochalasin D. The results showed that the elastic coefficients of HCC cells were obviously higher than the corresponding value of hepatocytes. By treating with colchicine, the effects on viscoelastic properties of HCC cells were obviously different in ways and extents from those on viscoelastic properties of hepatocytes.,but the viscoelastic properties of hepatocytes by treated with cytochalasin D had the same trend of decreasing as those of HCC cells. These results represent the change in cytoskeleton structure and function among hepatocytes and HCC cells, this change might affect tumor cells invasion and metastasis.
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The viscoelastic properties of hepatocellular carcinoma (HCC) cells were measured by means of micropipette aspiration technique. Further,the authors studied the changes in viscoelastic coefficients by treating with colchicine and cytochalasin D. The results showed that the elastic coefficients of HCC cells were obviously higher than the corresponding value of hepatocytes. By treating with colchicine, the effects on viscoelastic properties of HCC cells were obviously different in ways and extents from those on viscoelastic properties of hepatocytes.,but the viscoelastic properties of hepatocytes by treated with cytochalasin D had the same trend of decreasing as those of HCC cells. These results represent the change in cytoskeleton structure and function among hepatocytes and HCC cells, this change might affect tumor cells invasion and metastasis.