scholarly journals Condensation tendency of connected contractile tissue with planar isotropic actin network

2020 ◽  
Author(s):  
Tianfa Xie ◽  
Sarah R. St. Pierre ◽  
Nonthakorn Olaranont ◽  
Lauren E. Brown ◽  
Min Wu ◽  
...  
Keyword(s):  
Cell Stiffness ◽  
Actin Network ◽  
Cell Contractility ◽  
Differential Cell ◽  
New Type ◽  
Adhesive Interactions ◽  
Planar Substrates ◽  
Nih 3T3 ◽  
Embryonic Fibroblast ◽  
Contractile Tissue

ABSTRACTIt has been found that many types of cells form nematic symmetry on confined planar substrates. Such observation has been satisfactorily explained by modeling cells as crowded self-propelled rods. In this work, we report that rat embryonic fibroblast (REF) cells when confined in circular mesoscale patterns, form a new type of symmetry where cells align radially at the boundary. Unlike NIH-3T3 and MDCK monolayers, the REF monolayer presents a supracellular actin gradient with isotropic meshwork. In addition, the contractile REF cells present strong adhesive interactions with neighboring cells, which confers the monolayer with significant condensation tendency. We found the loss of condensation tendency by inhibiting the cell contractility or disrupting cell-cell adhesion led to the disappearance of the radial alignment. In theory, we found the prestretch due to condensation tendency with differential cell stiffness is sufficient to explain the new symmetry within a confined tissue continuum.

scholarly journals Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Tianfa Xie ◽  
Sarah R St Pierre ◽  
Nonthakorn Olaranont ◽  
Lauren E Brown ◽  
Min Wu ◽  
...  
Keyword(s):  
Cell Model ◽  
Orientational Order ◽  
Voronoi Cell ◽  
Cell Stiffness ◽  
Hydrodynamic Theory ◽  
Mechanical Equilibrium ◽  
Cortical Actin ◽  
Cell Contractility ◽  
3T3 Fibroblasts ◽  
Nih 3T3

A monolayer of highly motile cells can establish long-range orientational order, which can be explained by hydrodynamic theory of active gels and fluids. However, it is less clear how cell shape changes and rearrangement are governed when the monolayer is in mechanical equilibrium states when cell motility diminishes. In this work, we report that rat embryonic fibroblasts (REF), when confined in circular mesoscale patterns on rigid substrates, can transition from the spindle shapes to more compact morphologies. Cells align radially only at the pattern boundary when they are in the mechanical equilibrium. This radial alignment disappears when cell contractility or cell-cell adhesion is reduced. Unlike monolayers of spindle-like cells such as NIH-3T3 fibroblasts with minimal intercellular interactions or epithelial cells like Madin-Darby canine kidney (MDCK) with strong cortical actin network, confined REF monolayers present an actin gradient with isotropic meshwork, suggesting the existence of a stiffness gradient. In addition, the REF cells tend to condense on soft substrates, a collective cell behavior we refer to as the 'condensation tendency'. This condensation tendency, together with geometrical confinement, induces tensile prestretch (i.e., an isotropic stretch that causes tissue to contract when released) to the confined monolayer. By developing a Voronoi-cell model, we demonstrate that the combined global tissue prestretch and cell stiffness differential between the inner and boundary cells can sufficiently define the cell radial alignment at the pattern boundary.

scholarly journals A GTPase controls cell-substrate adhesion in Xenopus XTC fibroblasts.

1992 ◽  
Vol 118 (5) ◽  
pp. 1235-1244 ◽  
Author(s):  
M H Symons ◽  
T J Mitchison
Keyword(s):  
Control Cell ◽  
Response To Treatment ◽  
Nucleotide Analogs ◽  
Cell Contractility ◽  
Cell Rounding ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Adhesive Interactions ◽  
Cell Substrate Adhesion ◽  
Gamma S

Cell-substrate adhesion is crucial at various stages of development and for the maintenance of normal tissues. Little is known about the regulation of these adhesive interactions. To investigate the role of GTPases in the control of cell morphology and cell-substrate adhesion we have injected guanine nucleotide analogs into Xenopus XTC fibroblasts. Injection of GTP gamma S inhibited ruffling and increased spreading, suggesting an increase in adhesion. To further investigate this, we made use of GRGDSP, a peptide which inhibits binding of integrins to vitronectin and fibronectin. XTC fibroblasts injected with non-hydrolyzable analogs of GTP took much more time to round up than mock-injected cells in response to treatment with GRGDSP, while GDP beta S-injected cells rounded up in less time than controls. Injection with GTP gamma S did not inhibit cell rounding induced by trypsin however, showing that cell contractility is not significantly affected by the activation of GTPases. These data provide evidence for the existence of a GTPase which can control cell-substrate adhesion from the cytoplasm. Treatment of XTC fibroblasts with the phorbol ester 12-o-tetradecanoylphorbol-13-acetate reduced cell spreading and accelerated cell rounding in response to GRGDSP, which is essentially opposite to the effect exerted by non-hydrolyzable GTP analogs. These results suggest the existence of at least two distinct pathways controlling cell-substrate adhesion in XTC fibroblasts, one depending on a GTPase and another one involving protein kinase C.

scholarly journals Acrylamide Induced Oxidative Cellular Senescence in Embryonic Fibroblast Cell Line (NIH 3T3): A Protection by Carvacrol

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mehdi Evazalipour ◽  
Pouya Safarzadeh Kozani ◽  
Pooria Safarzadeh Kozani ◽  
Sahar Shabani ◽  
Bahar Rezaei Soufi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cell Line ◽  
Cellular Senescence ◽  
Fibroblast Cell ◽  
Protective Effects ◽  
Proliferating Cells ◽  
Beneficial Effects ◽  
Nih 3T3 ◽  
Embryonic Fibroblast

Background: Stress-induced cellular senescence is a perpetual state of cell cycle arrest occurring in proliferating cells in response to stressful conditions. It is believed that oxidative stress plays a unique role in this process. As a reactive chemical compound that can induce oxidative stress, acrylamide is widely applied in several fields. Carvacrol is a liquid phenolic monoterpenoid found in essential oils of some plants and is known for its antioxidant and anticarcinogenic properties. Objectives: The current study aimed to evaluate the effects of carvacrol on oxidative stress and cellular senescence induced by acrylamide in the NIH 3T3 cell line. Methods: NIH 3T3 embryonic fibroblast cells were exposed to different concentrations of acrylamide, carvacrol, and H2O2 in a cell culture medium. The level of β-galactosidase (SA-β-gal) activity, as a marker of cellular senescence, was measured using staining and quantitative assays. Furthermore, to measure oxidative stress parameters, the content of glutathione and lipid peroxidation were determined. Results: Acrylamide could induce premature senescence evident by the elevated lipid peroxidation and SA-β-gal activity and declined cell viability and glutathione. Moreover, carvacrol showed beneficial effects on both acrylamide- and H2O2-induced cellular senescence by significantly reversing or subsiding the effect of oxidative stress and mediating its consequences. Conclusions: It can be concluded that carvacrol has protective effects against oxidative cellular senescence induced by acrylamide in the NIH 3T3 cell line.

scholarly journals Phytochemical Characterization and Chemotherapeutic Potential of Cinnamomum verum Extracts on the Multiplication of Protozoan Parasites In Vitro and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 996 ◽  
Author(s):  
Gaber El-Saber Batiha ◽  
Amany Magdy Beshbishy ◽  
Azirwan Guswanto ◽  
Arifin Nugraha ◽  
Tserendorj Munkhjargal ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Inhibitory Effect ◽  
Mouse Embryonic Fibroblast ◽  
Bioactive Constituents ◽  
Viability Assay ◽  
Nih 3T3 ◽  
Embryonic Fibroblast ◽  
Herbal Plant

Cinnamomum verum is a commonly used herbal plant that has several documented properties against various diseases. The existing study evaluated the inhibitory effect of acetonic extract of C. verum (AECV) and ethyl acetate extract of C. verum (EAECV) against piroplasm parasites in vitro and in vivo. The drug-exposure viability assay was tested on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3) and human foreskin fibroblast (HFF) cells. Qualitative phytochemical estimation revealed that AECV and EAECV containing multiple bioactive constituents namely alkaloids, tannins, saponins, terpenoids and remarkable amounts of polyphenols and flavonoids. AECV and EAECV inhibited B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi multiplication at half-maximal inhibitory concentrations (IC50) of 23.1 ± 1.4, 56.6 ± 9.1, 33.4 ± 2.1, 40.3 ± 7.5, 18.8 ± 1.6 µg/mL, and 40.1 ± 8.5, 55.6 ± 1.1, 45.7 ± 1.9, 50.2 ± 6.2, and 61.5 ± 5.2 µg/mL, respectively. In the cytotoxicity assay, AECV and EAECV affected the viability of MDBK, NIH/3T3 and HFF cells with half-maximum effective concentrations (EC50) of 440 ± 10.6, 816 ± 12.7 and 914 ± 12.2 µg/mL and 376 ± 11.2, 610 ± 7.7 and 790 ± 12.4 µg/mL, respectively. The in vivo experiment showed that AECV and EAECV were effective against B. microti in mice at 150 mg/kg. These results showed that C. verum extracts are potential antipiroplasm drugs after further studies in some clinical cases.

scholarly journals oxLDL-induced decrease in lipid order of membrane domains is inversely correlated with endothelial stiffness and network formation

2010 ◽  
Vol 299 (2) ◽  
pp. C218-C229 ◽  
Author(s):  
Tzu Pin Shentu ◽  
Igor Titushkin ◽  
Dev K. Singh ◽  
Keith J. Gooch ◽  
Papasani V. Subbaiah ◽  
...  
Keyword(s):  
Network Formation ◽  
Cell Stiffness ◽  
Membrane Domains ◽  
Collagen Gels ◽  
Lipid Packing ◽  
Angiogenic Potential ◽  
Cell Contractility ◽  
Lipid Order ◽  
The Impact ◽  
Endothelial Stiffness

Oxidized low-density lipoprotein (oxLDL) is a major factor in development of atherosclerosis. Our earlier studies have shown that exposure of endothelial cells (EC) to oxLDL increases EC stiffness, facilitates the ability of the cells to generate force, and facilitates EC network formation in three-dimensional collagen gels. In this study, we show that oxLDL induces a decrease in lipid order of membrane domains and that this effect is inversely correlated with endothelial stiffness, contractility, and network formation. Local lipid packing of cell membrane domains was assessed by Laurdan two-photon imaging, endothelial stiffness was assessed by measuring cellular elastic modulus using atomic force microscopy, cell contractility was estimated by measuring the ability of the cells to contract collagen gels, and EC angiogenic potential was estimated by visualizing endothelial networks within the same gels. The impact of oxLDL on endothelial biomechanics and network formation is fully reversed by supplying the cells with a surplus of cholesterol. Furthermore, exposing the cells to 7-keto-cholesterol, a major oxysterol component of oxLDL, or to another cholesterol analog, androstenol, also results in disruption of lipid order of membrane domains and an increase in cell stiffness. On the basis of these observations, we suggest that disruption of lipid packing of cholesterol-rich membrane domains plays a key role in oxLDL-induced changes in endothelial biomechanics.

scholarly journals Design, Synthesis and Anti-Lung Cancer Evaluation of 1, 2, 3-Triazole Tethered Dihydroartemisinin-Isatin Hybrids

2021 ◽  
Vol 12 ◽  
Author(s):  
Haodong Hou ◽  
Bin Qu ◽  
Chen Su ◽  
Guihua Hou ◽  
Feng Gao
Keyword(s):  
Lung Cancer ◽  
Liver Microsomes ◽  
Parent Drug ◽  
Mouse Embryonic Fibroblast ◽  
Lung Cancer Cell ◽  
Design Synthesis ◽  
Pharmacokinetic Properties ◽  
Nih 3T3 ◽  
Embryonic Fibroblast ◽  
Excellent Stability

A series of 1,2,3-triazole tethered dihydroartemisinin-isatin hybrids 8a-c and 9a-k were designed and synthesized. Their antiproliferative activity against A549, doxorubicin-resistant A549 (A549/DOX) as well as cisplatin-resistant A549 (A549/DDP) lung cancer cell lines was also investigated in this study. All hybrids (half maximal inhibitory concentration/IC50: 7.54–73.8 μM) were more potent than the parent drug dihydroartemisinin (IC50: 69.4–88.0 μM) and also non-cytotoxic towards mouse embryonic fibroblast cells NIH/3T3 (IC50: >100 μM). The structure-activity relationships illustrated that the substituents on C-3 and C-5 position of isatin moiety influenced the activity significantly. Imine at C-3 position decreased the activity, whereas fluoro at C-5 position enhanced the activity. In particular, hybrids 8a,c (IC50: 7.54–12.1 μM) and 9i (IC50: 9.10–15.9 μM) were comparable to cisplatin (IC50: 7.54–15.9 μM vs 9.38–19.7 μM) against A549 and A549/DOX, but 4.6–7.6 folds more potent than that of cisplatin (IC50: 8.77–14.3 μM vs 66.9 μM) against A549/DDP cells. Moreover, hybrids 8a,c exhibited excellent stability (liver microsomes: 68–83%) in mouse/human microsomes and good pharmacokinetic properties, demonstrating their potential as a novel anti-lung cancer chemotherapeutic candidates.

scholarly journals Therapeutic Effects of Atranorin towards the Proliferation of Babesia and Theileria Parasites

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 127 ◽  
Author(s):  
Amany Magdy Beshbishy ◽  
Gaber El-Saber Batiha ◽  
Luay Alkazmi ◽  
Eman Nadwa ◽  
Eman Rashwan ◽  
...  
Keyword(s):  
Mouse Embryonic Fibroblast ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Diminazene Aceturate ◽  
Human Foreskin Fibroblasts ◽  
Ic50 Values ◽  
Nih 3T3 ◽  
Embryonic Fibroblast

Atranorin (ATR), is a compound with multidirectional biological activity under different in vitro and in vivo conditions and it is effective as an antibacterial, antiviral, antiprotozoal and anti-inflammatory agent. In the current study, the in vitro as well as in vivo chemotherapeutic effect of ATR as well as its combined efficacy with the existing antibabesial drugs (diminazene aceturate (DA), atovaquone (AV) and clofazimine (CF)) were investigated on six species of piroplasm parasites. ATR suppressed B. bovis, B. bigemina, B. divergens, B. caballi and T. equi multiplication in vitro with IC50 values of 98.4 ± 4.2, 64.5 ± 3.9, 45.2 ± 5.9, 46.6 ± 2.5, and 71.3 ± 2.7 µM, respectively. The CCK test was used to examine ATR’s cytotoxicity and adverse effects on different animal and human cell lines, the main hosts of piroplasm parasites and it showed that ATR affected human foreskin fibroblasts (HFF), mouse embryonic fibroblast (NIH/3T3) and Madin-Darby Bovine Kidney (MDBK) cell viability in a dose-related effect with a moderate selective index. The combined efficacy of ATR with DA, CF, and AV exhibited a synergistic and additive efficacy toward all tested species. In the in vivo experiment, ATR prohibited B. microti multiplication in mice by 68.17%. The ATR-DA and ATR-AV combination chemotherapies were more potent than ATR monotherapy. These results indicate the prospects of ATR as a drug candidate for piroplasmosis treatment.

scholarly journals Short antimicrobial peptidomimetic SAMP-5 effective against multidrug-resistant gram-negative bacteria

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eun Young Kim ◽  
So Hee Han ◽  
Jong Min Kim ◽  
Seon-Myung Kim ◽  
Song Yub Shin
Keyword(s):  
Mammalian Cells ◽  
Serial Passage ◽  
Multidrug Resistant ◽  
Mouse Embryonic Fibroblast ◽  
Proteinase K ◽  
Gram Negative Bacteria ◽  
Promising Alternative ◽  
Gram Negative ◽  
Nih 3T3 ◽  
Embryonic Fibroblast

AbstractSAMP-5 is a short histidine-derived antimicrobial peptidomimetic with pendant dialkylated tail. In this study, we evaluated the potential of SAMP-5 as an antimicrobial agent to combat multidrug-resistant gram-negative bacteria. SAMP-5 showed potent antimicrobial activity (minimum inhibitory concentration 16-64 μg/ml) comparable to melittin against multidrug-resistant Escherichia coli (MDREC) and multidrug-resistant (MDRPA). SAMP-5 displayed no cytotoxicity against three mammalian cells such as mouse macrophage RAW264.7, mouse embryonic fibroblast NIH-3T3, and human bone marrow SH-SY5Y cells at the concentration of 128 μg/ml. SAMP-5 showed resistance to proteolytic degradation with pepsin, trypsin, α-chymotrypsin, and proteinase K. Importantly, unlike ciprofloxacin, no antibiotic resistance against SAMP-5 arose for Pseudomonas aeruginosa during 7 days of serial passage at 0.5 × MIC. Moreover, SAMP-5 showed synergy or additive effects against MDRPA and MDREC, when it combined with chloramphenicol, ciprofloxacin, and oxacillin. Collectively, our results suggested that SAMP-5 is a promising alternative and adjuvant to treat infections caused by multidrug-resistant gram-negative bacteria.

scholarly journals Cellular contractility coordinates cytoskeletal dynamics and cell behaviour during Drosophila abdominal morphogenesis

2019 ◽  
Author(s):  
◽  
Anneliese Norris ◽  
Marcus Bischoff
Keyword(s):  
Epithelial Cells ◽  
Rho Gtpase ◽  
Behavioural Change ◽  
Actin Network ◽  
Cell Behaviour ◽  
Cell Contractility ◽  
Cytoskeletal Dynamics ◽  
In Cells

AbstractDuring morphogenesis, cells undergo various behaviours, such as migration and constriction, which need to be coordinated. How this is achieved remains elusive. During morphogenesis of the Drosophila adult abdominal epidermis, larval epithelial cells (LECs) migrate directedly before constricting apically and undergoing apoptosis. Here, we study the mechanisms underlying the transition from migration to constriction. We show that LECs possess a pulsatile apical actomyosin network and that a change in network polarity underlies behavioural change. Exploring the properties of the contractile network, we find that the level of cell contractility impacts on the network’s behaviour, as well as on overall cytoskeletal architecture and cell behaviour. We also find that pulsed contractions occur only in cells with intermediate levels of contractility. Furthermore, increasing levels of the small Rho GTPase Rho1 disrupts pulsed contractions, and instead leading to cells that cycle between two states, characterised by a junctional cortical and an apicomedial actin network. Our results highlight that behavioural change relies on tightly controlled cellular contractility. Moreover, we show that constriction can occur without pulsed contractions, raising questions about their contribution to constriction.

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