scholarly journals Traction Forces Control Cell-Edge Dynamics and Mediate Distance-Sensitivity During Cell Polarization

2019 ◽  
Author(s):  
Zeno Messi ◽  
Alicia Bornert ◽  
Franck Raynaud ◽  
Alexander B. Verkhovsky
Keyword(s):  
Control Cell ◽  
Cell Polarization ◽  
Traction Forces ◽  
Cell Edge

scholarly journals Traction Forces Control Cell-Edge Dynamics and Mediate Distance Sensitivity during Cell Polarization

2020 ◽  
Vol 30 (9) ◽  
pp. 1762-1769.e5 ◽  
Author(s):  
Zeno Messi ◽  
Alicia Bornert ◽  
Franck Raynaud ◽  
Alexander B. Verkhovsky
Keyword(s):  
Control Cell ◽  
Cell Polarization ◽  
Traction Forces ◽  
Cell Edge

scholarly journals Traction forces control cell-edge dynamics and mediate distance-sensitivity during cell polarization

2019 ◽  
Author(s):  
Zeno Messi ◽  
Alicia Bornert ◽  
Franck Raynaud ◽  
Alexander Verkhovsky
Keyword(s):  
Control Cell ◽  
Focal Adhesions ◽  
Cell Polarization ◽  
Matrix Remodeling ◽  
Traction Forces ◽  
Cell Edge ◽  
Cell Parameters ◽  
Cell Contractility ◽  
Edge Behavior ◽  
Shape Changes

SUMMARYTraction forces are generated by cellular actin-myosin system and transmitted to the environment through adhesions. They are believed to drive cell motion, shape changes, and extracellular matrix remodeling [1–3]. However, most of the traction force analysis has been performed on stationary cells, investigating forces at the level of individual focal adhesions or linking them to static cell parameters such as area and edge curvature [4–10]. It is not well understood how traction forces are related to shape changes and motion, e.g. forces were reported to either increase or drop prior to cell retraction [11–15]. Here, we analyze the dynamics of traction forces during the protrusion-retraction cycle of polarizing fish epidermal keratocytes and find that forces fluctuate in concert with the cycle, increasing during the protrusion phase and reaching maximum at the beginning of retraction. We relate force dynamics to the recently discovered phenomenological rule [16] that governs cell edge behavior during keratocyte polarization: both traction forces and the probability of switch from protrusion to retraction increase with the distance from the cell center. Diminishing traction forces with cell contractility inhibitor leads to decreased edge fluctuations and abnormal polarization, while externally applied force can induce protrusion-retraction switch. These results suggest that forces mediate distance-sensitivity of the edge dynamics and ultimately organize cell-edge behavior leading to spontaneous polarization. Actin flow rate did not exhibit the same distance-dependence as traction stress, arguing against its role in organizing edge dynamics. Finally, using a simple model of actin-myosin network, we show that force-distance relationship may be an emergent feature of such networks.

scholarly journals Cdc42 and Par6–PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization

2005 ◽  
Vol 170 (6) ◽  
pp. 895-901 ◽  
Author(s):  
Sandrine Etienne-Manneville ◽  
Jean-Baptiste Manneville ◽  
Sarah Nicholls ◽  
Michael A. Ferenczi ◽  
Alan Hall
Keyword(s):  
Total Internal Reflection ◽  
Biochemical Analysis ◽  
Control Cell ◽  
Leading Edge ◽  
Cell Polarization ◽  
Physical Interaction ◽  
Biological Processes ◽  
Polyposis Coli ◽  
Tumor Suppressor Proteins ◽  
Wide Range

Cell polarization is essential in a wide range of biological processes such as morphogenesis, asymmetric division, and directed migration. In this study, we show that two tumor suppressor proteins, adenomatous polyposis coli (APC) and Dlg1-SAP97, are required for the polarization of migrating astrocytes. Activation of the Par6–PKCζ complex by Cdc42 at the leading edge of migrating cells promotes both the localized association of APC with microtubule plus ends and the assembly of Dlg-containing puncta in the plasma membrane. Biochemical analysis and total internal reflection fluorescence microscopy reveal that the subsequent physical interaction between APC and Dlg1 is required for polarization of the microtubule cytoskeleton.

scholarly journals Classical cadherins control nucleus and centrosome position and cell polarity

2009 ◽  
Vol 185 (5) ◽  
pp. 779-786 ◽  
Author(s):  
Isabelle Dupin ◽  
Emeline Camand ◽  
Sandrine Etienne-Manneville
Keyword(s):  
Cell Polarity ◽  
Control Cell ◽  
Cell Types ◽  
Free Cell ◽  
Cell Polarization ◽  
Cell Interactions ◽  
Spatial Cues ◽  
Cell Contacts ◽  
Classical Cadherins ◽  
Cell Cell

Control of cell polarity is crucial during tissue morphogenesis and renewal, and depends on spatial cues provided by the extracellular environment. Using micropatterned substrates to impose reproducible cell–cell interactions, we show that in the absence of other polarizing cues, cell–cell contacts are the main regulator of nucleus and centrosome positioning, and intracellular polarized organization. In a variety of cell types, including astrocytes, epithelial cells, and endothelial cells, calcium-dependent cadherin-mediated cell–cell interactions induce nucleus and centrosome off-centering toward cell–cell contacts, and promote orientation of the nucleus–centrosome axis toward free cell edges. Nucleus and centrosome off-centering is controlled by N-cadherin through the regulation of cell interactions with the extracellular matrix, whereas the orientation of the nucleus–centrosome axis is determined by the geometry of N-cadherin–mediated contacts. Our results demonstrate that in addition to the specific function of E-cadherin in regulating baso-apical epithelial polarity, classical cadherins control cell polarization in otherwise nonpolarized cells.

scholarly journals Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions

2021 ◽  
Author(s):  
Hendrik Boog ◽  
Rebecca Medda ◽  
Elisabetta Ada Cavalcanti-Adam
Keyword(s):  
Signaling Pathways ◽  
Single Cells ◽  
Center Of Mass ◽  
Control Cell ◽  
Culture Conditions ◽  
Cell Polarization ◽  
Receptor Complexes ◽  
Cell Shapes ◽  
Distribution Studies ◽  
Receptor Distribution

At the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane is crucial for the regulation of signaling and cell behavior. However, it is challenging to define what regulates such spatial patterns for receptor localization, as cell shapes are extremely diverse when cells are maintained in standard culture conditions. Bone morphogenic protein receptors (BMPRs) are serine-threonine kinases, which build heteromeric complexes of BMPRI and II. These are especially interesting targets for receptor distribution studies, since the signaling pathways triggered by BMPR-complexes depends on their dimerization mode. They might exist as pre-formed complexes, or assemble upon binding of BMP, triggering cell signaling which leads to differentiation or migration. In this work we analyzed BMPR receptor distributions in single cells grown on micropatterns, which allows not only to control cell shape, but also the distribution of intracellular organelles and protein assemblies. We developed a script called ComRed (Center Of Mass Receptor Distribution), which uses center of mass calculations to analyze the shift and spread of receptor distributions according to the different cell shapes. ComRed was tested by simulating changes in experimental data, showing that shift and spread of distributions can be reliably detected. Our ComRed-based analysis of BMPR-complexes indicates that receptor distribution depends on cell polarization. The absence of a coordinated internalization after addition of BMP suggests that a rapid and continual recycling of BMPRs occurs. Receptor complexes formation and localization in cells induced by BMP might yield insights into the local regulation of different signaling pathways.

scholarly journals Spots, stripes, and spiral waves in models for static and motile cells

2021 ◽  
Vol 82 (4) ◽  
Author(s):  
Yue Liu ◽  
Elisabeth G. Rens ◽  
Leah Edelstein-Keshet
Keyword(s):  
Cell Polarization ◽  
Spiral Waves ◽  
Eukaryotic Cells ◽  
Filamentous Actin ◽  
Cell Edge ◽  
Sources And Sinks ◽  
Spontaneous Formation ◽  
Motile Cells ◽  
Dynamic Cell ◽  
Cell Shapes

AbstractThe polarization and motility of eukaryotic cells depends on assembly and contraction of the actin cytoskeleton and its regulation by proteins called GTPases. The activity of GTPases causes assembly of filamentous actin (by GTPases Cdc42, Rac), resulting in protrusion of the cell edge. Mathematical models for GTPase dynamics address the spontaneous formation of patterns and nonuniform spatial distributions of such proteins in the cell. Here we revisit the wave-pinning model for GTPase-induced cell polarization, together with a number of extensions proposed in the literature. These include introduction of sources and sinks of active and inactive GTPase (by the group of A. Champneys), and negative feedback from F-actin to GTPase activity. We discuss these extensions singly and in combination, in 1D, and 2D static domains. We then show how the patterns that form (spots, waves, and spirals) interact with cell boundaries to create a variety of interesting and dynamic cell shapes and motion.

scholarly journals Substrate Resistance to Traction Forces Controls Fibroblast Polarization

2020 ◽  
Author(s):  
D. Missirlis ◽  
T. Haraszti ◽  
L. Heckmann ◽  
J. P. Spatz
Keyword(s):  
Mechanical Properties ◽  
Surface Layer ◽  
Focal Adhesion ◽  
Human Fibroblasts ◽  
Traction Force ◽  
Cell Polarization ◽  
Cell Physiology ◽  
Traction Forces ◽  
Cellular Processes ◽  
Cell Mechanosensing

AbstractThe mechanics of fibronectin-rich extracellular matrix regulate cell physiology in a number of diseases, prompting efforts to elucidate cell mechanosensing mechanisms at the molecular and cellular scale. Here, the use of fibronectin-functionalized silicone elastomers that exhibit considerable frequency-dependence in viscoelastic properties unveiled the presence of two cellular processes that respond discreetly to substrate mechanical properties. Soft elastomers supported efficient focal adhesion maturation and fibroblast spreading due to an apparent stiff surface layer. However, soft elastomers did not enable cytoskeletal and fibroblast polarization; elastomers with high cross-linking and low deformability were required for polarization. The underlying reason for this behavior was the inability of soft elastomeric substrates to resist traction forces, rather than a lack of sufficient traction force generation; accordingly, mild inhibition of actomyosin contractility rescued fibroblast polarization even on the softer elastomers. Our findings help reconcile previously proposed local and global models of cell mechanosensing by demonstrating the differential dependence of substrate mechanics on distinct cellular processes.Statement of SignificanceThe mechanisms cells employ to sense and respond to the mechanical properties of their surroundings remain incompletely understood. In this study we used a commercial silicone elastomer formulation to prepare compliant, fibronectin-coated substrates and investigate the adhesion and polarization of human fibroblasts. Our results suggest the existence of at least two discrete mechanosensing processes regulated at different time and length (force) scales. Focal adhesion assembly and cell spreading were promoted by a stiff surface layer independent from bulk viscoelasticity, whereas effective cell polarization required elevated elastomer stiffness, sufficient to resist applied cell traction. The results presented here have implications on the use of elastomeric substrates as biomaterials for mechanosensing studies or clinical applications.

scholarly journals ROLE OF CXCR3 CHEMOKINE RECEPTOR AND ITS LIGANDS IN CERTAIN DISEASES

2019 ◽  
Vol 21 (4) ◽  
pp. 617-632 ◽  
Author(s):  
N. A. Arsentieva ◽  
A. V. Semenov ◽  
D. A. Zhebrun ◽  
E. V. Vasilyeva ◽  
Areg A. Totolian
Keyword(s):  
Immune Responses ◽  
Chemokine Receptor ◽  
Wide Spectrum ◽  
Control Cell ◽  
Autoimmune Disorders ◽  
Cell Polarization ◽  
Main Function ◽  
Activated T Cells ◽  
Wide Range

Chemokines are a special family of cytokines whose main function is to control cell migration; they are key players in the innate and adaptive immune responses. Directed chemotaxis of specific leukocyte subpopulations is necessary not only to maintain homeostasis, but also in development of some immunopathological conditions such as cancer, inflammation, infection, allergies and autoimmune disorders. Chemokines are pleiotropic molecules that are involved in physiological and pathophysiological processes. For example, the CXCR3 chemokine receptor is expressed on various cells: activated T and B lymphocytes, natural killers, eosinophils and neutrophils, dendritic cells, fibroblasts, endothelial and epithelial cells. Hence, CXCR3 and its ligands have a wide range of functional activity. CXCR3 ligands are the IFNγ-induced chemokines: CXCL9, CXCL10, CXCL11, and platelet-derived chemokines: CXCL4, CXCL4L1. All the CXCR3 ligands share common angiostatic properties due to lack of the Glu-Leu-Arg (ELR) motif. IFNγ-induced ligands of the CXCR3 are proinflammatory chemokines, they mainly recruit activated T cells and exert an effect on T cell polarization. Due to wide spectrum of biological activity, the ligands of CXCR3 receptor are involved in pathogenesis of various disorders, such as inflammation, infection, cancer, allergies and autoimmune disorders. In this review, we discuss the role of CXCR3 ligands in immunopathogenesis of various diseases, including the results of our studies in chronic hepatitis C, rheumatoid arthritis and pulmonary tuberculosis. Moreover, we have also discussed the potential laboratory diagnostic applicability of the chemokines in various diseases. This review illustrates a universal role of IFNγ-induced chemokines as mediators of immune responses in various diseases. The studies of CXCR3 ligands, their isoforms and receptors, interactions between themselves and with their receptors can provide a significant contribution to our understanding of the chemokine network. Understanding the system of IFNγ-dependent chemokines may have clinical implications, both for diagnostic tasks, and for therapeutic purposes.

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