scholarly journals Statins Perturb Gβγ Signaling and Cell Behavior in a Gγ Subtype Dependent Manner

2019 ◽  
Vol 95 (4) ◽  
pp. 361-375 ◽  
Author(s):  
Mithila Tennakoon ◽  
Dinesh Kankanamge ◽  
Kanishka Senarath ◽  
Zehra Fasih ◽  
Ajith Karunarathne
Keyword(s):  
Cell Behavior ◽  
Dependent Manner

scholarly journals Synergistic Modulation of Cellular Contractility by Mixed Extracellular Matrices

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Aastha Kapoor ◽  
Shamik Sen
Keyword(s):  
Mixed Ligand ◽  
Matrix Proteins ◽  
Extracellular Matrices ◽  
Cell Behavior ◽  
Dependent Manner ◽  
Cell Contractility ◽  
Synergistic Modulation ◽  
Coated Surfaces ◽  
Collective Influence

The extracellular matrix (ECM) is known to provide various physicochemical cues in directing cell behavior including composition, topography, and dimensionality. Physical remodeling of the ECM has been documented in a variety of cancers. In breast cancer, the increased deposition of matrix proteins, their crosslinking, and alignment create a stiffer microenvironment that activates cell contractility and promotes cancer invasion. In this paper, we sought to study the collective influence of ECM composition and density on the contractile mechanics of human MDA-MB-231 cells making use of the recently established trypsin deadhesion assay. Using collagen and fibronectin-coated surfaces of varying density, we show that cell contractility is tuned in a density-dependent manner, with faster deadhesion on fibronectin-coated surfaces compared to collagen-coated surfaces under identical coating densities. The deadhesion responses are significantly delayed when cells are treated with the myosin inhibitor blebbistatin. By combining collagen and fibronectin at two different densities, we show that mixed ligand surfaces synergistically modulate cell contractility. Finally, we show that on fibroblast-derived 3D matrices that closely mimicin vivomatrices, cells are strongly polarized and exhibit faster deadhesion compared to the mixed ligand surfaces. Together, our results demonstrate that ECM composition, density, and 3D organization collectively regulate cell contractility.

scholarly journals Homologous locus pairing is a transient, diffusion-mediated process in meiotic prophase

2021 ◽  
Author(s):  
Trent A. C. Newman ◽  
Bruno Beltran ◽  
James M. McGehee ◽  
Daniel Elnatan ◽  
Cori K. Cahoon ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Single Cell ◽  
Chromosome Pairing ◽  
Polymer Physics ◽  
Cell Behavior ◽  
Dependent Manner ◽  
Single Linkage ◽  
Fluorescent Reporter ◽  
Homologous Chromosomes ◽  
Prophase I

AbstractThe pairing of homologous chromosomes in meiosis I is essential for sexual reproduction and is mediated, in part, by the formation and repair of Spo11-induced DNA double strand breaks (DSBs). In budding yeast, each cell receives ~150-200 DSBs, yet only a fraction go on to form crossover products. How and why the cell initially co-ordinates so many interactions along each chromosome is not well understood. Using a fluorescent reporter-operator system (FROS), we measure the kinetics of interacting homologous loci at various stages of meiosis. We find that while tagged loci undergo considerable motion throughout prophase I, they are constrained in how far they can diffuse from their homolog pair. This effective tethering radius decreases over the course of meiosis in a DSB-dependent manner. We develop a theoretical model that captures the biological contributions of centromere attachment to the nuclear envelope, homolog pairing, and nuclear confinement. With this model, we demonstrate that the experimentally observed heterogeneity in single-cell behavior and the effective tethering between loci is captured for two polymers forming randomly-spaced linkages. The small number of connections required to reproduce our data demonstrates that a single linkage site between homologous chromosomes can constrain the movement of loci up to hundreds of kilobases away.Significance StatementMeiosis is essential for sexual reproduction, and homologous chromosome pairing is a critical step in this process that must be reliably achieved. We measure the dynamics of homologous loci throughout prophase I of meiosis, demonstrating the transient nature of homolog contacts and heterogeneity in single-cell behavior. We develop a minimal model containing only the basic polymer physics of DNA but is sufficient to reproduce the observed behavior. We show that it only takes a handful of homologous linkages per chromosome to facilitate pairing, demonstrating that a single tethered locus can drastically restrict the diffusion of DNA tens to hundreds of kilobases away. These results demonstrate the central role of random diffusion and polymer physics in facilitating chromosome pairing in meiosis.

scholarly journals The Role of Stiffness in Cell Reprogramming: A Potential Role for Biomaterials in Inducing Tissue Regeneration

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1036 ◽  
Author(s):  
Michele d’Angelo ◽  
Elisabetta Benedetti ◽  
Maria Grazia Tupone ◽  
Mariano Catanesi ◽  
Vanessa Castelli ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Tissue Regeneration ◽  
Cell Biology ◽  
New Technologies ◽  
Biomechanical Properties ◽  
Cell Reprogramming ◽  
Cell Behavior ◽  
Dependent Manner ◽  
Mechanical Stimuli

The mechanotransduction is the process by which cells sense mechanical stimuli such as elasticity, viscosity, and nanotopography of extracellular matrix and translate them into biochemical signals. The mechanotransduction regulates several aspects of the cell behavior, including migration, proliferation, and differentiation in a time-dependent manner. Several reports have indicated that cell behavior and fate are not transmitted by a single signal, but rather by an intricate network of many signals operating on different length and timescales that determine cell fate. Since cell biology and biomaterial technology are fundamentals in cell-based regenerative therapies, comprehending the interaction between cells and biomaterials may allow the design of new biomaterials for clinical therapeutic applications in tissue regeneration. In this work, we present the most relevant mechanism by which the biomechanical properties of extracellular matrix (ECM) influence cell reprogramming, with particular attention on the new technologies and materials engineering, in which are taken into account not only the biochemical and biophysical signals patterns but also the factor time.

scholarly journals Evidence That β3 Integrin-Induced Rac Activation Involves the Calpain-Dependent Formation of Integrin Clusters That Are Distinct from the Focal Complexes and Focal Adhesions That Form as Rac and Rhoa Become Active

2000 ◽  
Vol 151 (3) ◽  
pp. 685-696 ◽  
Author(s):  
Katarzyna Bialkowska ◽  
Sucheta Kulkarni ◽  
Xiaoping Du ◽  
Darrel E. Goll ◽  
Takaomi C. Saido ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Binding Protein ◽  
Focal Adhesions ◽  
Protein S ◽  
Integrin Signaling ◽  
Cell Behavior ◽  
Dependent Manner ◽  
Independent Mechanism ◽  
Β3 Integrin ◽  
Calpain Inhibitors

Interaction of integrins with the extracellular matrix leads to transmission of signals, cytoskeletal reorganizations, and changes in cell behavior. While many signaling molecules are known to be activated within Rac-induced focal complexes or Rho-induced focal adhesions, the way in which integrin-mediated adhesion leads to activation of Rac and Rho is not known. In the present study, we identified clusters of integrin that formed upstream of Rac activation. These clusters contained a Rac-binding protein(s) and appeared to be involved in Rac activation. The integrin clusters contained calpain and calpain-cleaved β3 integrin, while the focal complexes and focal adhesions that formed once Rac and Rho were activated did not. Moreover, the integrin clusters were dependent on calpain for their formation. In contrast, while Rac- and Rho-GTPases were dependent on calpain for their activation, formation of focal complexes and focal adhesions by constitutively active Rac or Rho, respectively, occurred even when calpain inhibitors were present. Taken together, these data are consistent with a model in which integrin-induced Rac activation requires the formation of integrin clusters. The clusters form in a calpain-dependent manner, contain calpain, calpain-cleaved integrin, and a Rac binding protein(s). Once Rac is activated, other integrin signaling complexes are formed by a calpain-independent mechanism(s).

Immunogold labeling of the calcium binding protein synexin in isolated adrenal chromaffin granules and chromaffin cells

1990 ◽  
Vol 48 (3) ◽  
pp. 952-953
Author(s):  
Gemma A.J. Kuijpers ◽  
Harvey B. Pollard
Keyword(s):  
Adrenal Medulla ◽  
Calcium Binding ◽  
Chromaffin Cells ◽  
Cell Activation ◽  
Structural Information ◽  
Dependent Manner ◽  
Chromaffin Granules ◽  
Immuno Electron Microscopy ◽  
Ultrathin Sections ◽  
Adrenal Chromaffin

Exocytotic fusion of granules in the adrenal medulla chromaffin cell is triggered by a rise in the concentration of cytosolic Ca2+ upon cell activation. The protein synexin, annexin VII, was originally found in the adrenal medulla and has been shown to cause aggregation and to support fusion of chromaffin granules in a Ca2+-dependent manner. We have previously suggested that synexin may there fore play a role in the exocytotic fusion process. In order to obtain more structural information on synexin, we performed immuno-electron microscopy on frozen ultrathin sections of both isolated chromaffin granules and chromaffin cells.Chromaffin granules were isolated from bovine adrenal medulla, and synexin was isolated from bovine lung. Granules were incubated in the presence or absence of synexin (24 μg per mg granule protein) and Ca2+ (1 mM), which induces maximal granule aggregation, in 0.3M sucrose-40m MMES buffer(pH 6.0). Granules were pelleted, washed twice in buffer without synexin and fixed with 2% glutaraldehyde- 2% para formaldehyde in 0.1 M phosphate buffer (GA/PFA) for 30 min. Chromaffin cells were isolated and cultured for 3-5 days, and washed and incubated in Krebs solution with or without 20 uM nicotine. Cells were fixed 90 sec after on set of stimulation with GA/PFA for 30 min. Fixed granule or cell pellets were washed, infiltrated with 2.3 M sucrose in PBS, mounted and frozen in liquid N2.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

Spindle scaling mechanisms

2020 ◽  
Vol 64 (2) ◽  
pp. 383-396
Author(s):  
Lara K. Krüger ◽  
Phong T. Tran
Keyword(s):  
Cell Size ◽  
Spindle Assembly ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Size Dependent ◽  
A Cell ◽  
Chromosome Separation ◽  
Spindle Elongation ◽  
Protein Gradients ◽  
Spindle Structure

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

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