The Experts below are selected from a list of 49077 Experts worldwide ranked by ideXlab platform
Gaudenz Danuser - One of the best experts on this subject based on the ideXlab platform.
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competition for actin between two distinct f actin networks defines a bistable switch for Cell polarization
Nature Cell Biology, 2015Co-Authors: Alexis J Lomakin, Kun Chun Lee, Sangyoon J Han, Duyen Amy Bui, Michael W Davidson, Alex Mogilner, Gaudenz DanuserAbstract:Symmetry-breaking polarization enables functional plasticity of Cells and tissues and is yet not well understood. Here we show that epithelial Cells, hard-wired to maintain a static morphology and to preserve tissue organization, can spontaneously switch to a migratory polarized phenotype after relaxation of the actomyosin cytoskeleton. We find that myosin II engages actin in the formation of cortical actomyosin bundles and thus makes it unavailable for deployment in the process of dendritic growth normally driving Cell motility. Under low-contractility regimes, epithelial Cells polarize in a front-back manner owing to the emergence of actin retrograde flows powered by dendritic polymerization of actin. Coupled to Cell movement, the flows transport myosin II from the front to the back of the Cell, where the motor locally 'locks' actin in contractile bundles. This polarization mechanism could be employed by embryonic and cancer epithelial Cells in microenvironments where high-contractility-driven Cell Motion is inefficient.
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competition for actin between two distinct f actin networks defines a bistable switch for Cell polarization
Nature Cell Biology, 2015Co-Authors: Alexis J Lomakin, Kun Chun Lee, Sangyoon J Han, Duyen Amy Bui, Michael W Davidson, Alex Mogilner, Gaudenz DanuserAbstract:Symmetry-breaking polarization enables functional plasticity of Cells and tissues and is yet not well understood. Here we show that epithelial Cells, hard-wired to maintain a static morphology and to preserve tissue organization, can spontaneously switch to a migratory polarized phenotype upon relaxation of the actomyosin cytoskeleton. We find that myosin-II engages actin in the formation of cortical actomyosin bundles and thus makes it unavailable for deployment in the process of dendritic growth normally driving Cell motility. At low contractility regimes epithelial Cells polarize in a front-back manner due to emergence of actin retrograde flows powered by dendritic polymerization of actin. Coupled to Cell movement, the flows transport myosin-II from the front to the back of the Cell, where the motor locally “locks” actin in contractile bundles. This polarization mechanism could be employed by embryonic and cancer epithelial Cells in microenvironments where high contractility-driven Cell Motion is inefficient.
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tracking retrograde flow in keratocytes news from the front
Molecular Biology of the Cell, 2005Co-Authors: Pascal Vallotton, Gaudenz Danuser, Jeanjacques Meister, Sophie Bohnet, Alexander B VerkhovskyAbstract:Actin assembly at the leading edge of the Cell is believed to drive protrusion, whereas membrane resistance and contractile forces result in retrograde flow of the assembled actin network away from the edge. Thus, Cell Motion and shape changes are expected to depend on the balance of actin assembly and retrograde flow. This idea, however, has been undermined by the reported absence of flow in one of the most spectacular models of Cell locoMotion, fish epidermal keratocytes. Here, we use enhanced phase contrast and fluorescent speckle microscopy and particle tracking to analyze the Motion of the actin network in keratocyte lamellipodia. We have detected retrograde flow throughout the lamellipodium at velocities of 1-3 microm/min and analyzed its organization and relation to the Cell Motion during both unobstructed, persistent migration and events of Cell collision. Freely moving Cells exhibited a graded flow velocity increasing toward the sides of the lamellipodium. In colliding Cells, the velocity decreased markedly at the site of collision, with striking alteration of flow in other lamellipodium regions. Our findings support the universality of the flow phenomenon and indicate that the maintenance of keratocyte shape during locoMotion depends on the regulation of both retrograde flow and actin polymerization.
C Pozrikidis - One of the best experts on this subject based on the ideXlab platform.
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numerical simulation of blood flow through microvascular capillary networks
Bulletin of Mathematical Biology, 2009Co-Authors: C PozrikidisAbstract:A numerical method is implemented for computing blood flow through a branching microvascular capillary network. The simulations follow the Motion of individual red blood Cells as they enter the network from an arterial entrance point with a specified tube hematocrit, while simultaneously updating the nodal capillary pressures. Poiseuille’s law is used to describe flow in the capillary segments with an effective viscosity that depends on the number of Cells residing inside each segment. The relative apparent viscosity is available from previous computational studies of individual red blood Cell Motion. Simulations are performed for a tree-like capillary network consisting of bifurcating segments. The results reveal that the probability of directional Cell Motion at a bifurcation (phase separation) may have an important effect on the statistical measures of the Cell residence time and scattering of the tube hematocrit across the network. Blood Cells act as regulators of the flow rate through the network branches by increasing the effective viscosity when the flow rate is high and decreasing the effective viscosity when the flow rate is low. Comparison with simulations based on conventional models of blood flow regarded as a continuum indicates that the latter underestimates the variance of the hematocrit across the vascular tree.
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numerical simulation of Cell Motion in tube flow
Annals of Biomedical Engineering, 2005Co-Authors: C PozrikidisAbstract:A theoretical model is presented for describing the Motion of a deformable Cell encapsulating a Newtonian fluid and enclosed by an elastic membrane in tube flow. In the mathematical formulation, the interior and exterior hydrodynamics are coupled with the membrane mechanics by means of surface equilibrium equations, and the problem is formulated as a system of integral equations for the interfacial velocity, the disturbance tube-wall traction, and the pressure difference across the two ends to the tube due to the presence of the Cell. Numerical solutions obtained by a boundary-element method are presented for flow in a cylindrical tube with a circular cross-section, cytoplasm viscosity equal to the ambient fluid viscosity, and Cells positioned sufficiently far from the tube wall so that strong lubrication forces do not arise. In the numerical simulations, Cells with spherical, oblate ellipsoidal, and biconcave unstressed shapes enclosed by membranes that obey a neo-Hookean constitutive equation are considered. Spherical Cells are found to slowly migrate toward the tube centerline at a rate that depends on the mean flow velocity, whereas oblate and biconcave Cells are found to develop parachute and slipper-like shapes, respectively, from axisymmetric and more general initial orientations.
Bertrand Benazeraf - One of the best experts on this subject based on the ideXlab platform.
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multi scale quantification of tissue behavior during amniote embryo axis elongation
Development, 2017Co-Authors: Mathias Beaupeux, Martin Tchernookov, Allison Wallingford, Tasha Salisbury, Amelia Shirtz, Dave Huss, Bertrand BenazerafAbstract:Embryonic axis elongation is a complex multi-tissue morphogenetic process responsible for the formation of the posterior part of the amniote body. How movements and growth are coordinated between the different posterior tissues (e.g. neural tube, axial and paraxial mesoderm, lateral plate, ectoderm, endoderm) to drive axis morphogenesis remain largely unknown. Here, we use quail embryos to quantify Cell behavior and tissue movements during elongation. We quantify the tissue-specific contribution to axis elongation using 3D volumetric techniques, then quantify tissue-specific parameters such as Cell density and proliferation. To study Cell behavior at a multi-tissue scale, we used high-resolution 4D imaging of transgenic quail embryos expressing fluorescent proteins. We developed specific tracking and image analysis techniques to analyze Cell Motion and compute tissue deformations in 4D. This analysis reveals extensive sliding between tissues during axis extension. Further quantification of tissue tectonics showed patterns of rotations, contractions and expansions, which are consistent with the multi-tissue behavior observed previously. Our approach defines a quantitative and multi-scale method to analyze the coordination between tissue behaviors during early vertebrate embryo morphogenetic events.
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a random Cell motility gradient downstream of fgf controls elongation of an amniote embryo
Nature, 2009Co-Authors: Bertrand Benazeraf, Paul Francois, Ruth E Baker, Nicolas Denans, Charles D Little, Olivier PourquieAbstract:Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive Cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled Cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of Cell motility and directionality in the PSM. We tracked the movement of the PSM extraCellular matrix in parallel with the labelled Cells and subtracted the extraCellular matrix movement from the global Motion of Cells. After subtraction, Cell motility remained graded but lacked directionality, indicating that the posterior Cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of Cell Motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient1, which has been implicated in the control of Cell motility in this tissue2. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with Cell movement inhibitors (blebbistatin or RhoK inhibitor), but not Cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random Cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random Cell Motion rather than by the regulation of directionality of individual Cellular movements.
Alex Mogilner - One of the best experts on this subject based on the ideXlab platform.
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competition for actin between two distinct f actin networks defines a bistable switch for Cell polarization
Nature Cell Biology, 2015Co-Authors: Alexis J Lomakin, Kun Chun Lee, Sangyoon J Han, Duyen Amy Bui, Michael W Davidson, Alex Mogilner, Gaudenz DanuserAbstract:Symmetry-breaking polarization enables functional plasticity of Cells and tissues and is yet not well understood. Here we show that epithelial Cells, hard-wired to maintain a static morphology and to preserve tissue organization, can spontaneously switch to a migratory polarized phenotype upon relaxation of the actomyosin cytoskeleton. We find that myosin-II engages actin in the formation of cortical actomyosin bundles and thus makes it unavailable for deployment in the process of dendritic growth normally driving Cell motility. At low contractility regimes epithelial Cells polarize in a front-back manner due to emergence of actin retrograde flows powered by dendritic polymerization of actin. Coupled to Cell movement, the flows transport myosin-II from the front to the back of the Cell, where the motor locally “locks” actin in contractile bundles. This polarization mechanism could be employed by embryonic and cancer epithelial Cells in microenvironments where high contractility-driven Cell Motion is inefficient.
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competition for actin between two distinct f actin networks defines a bistable switch for Cell polarization
Nature Cell Biology, 2015Co-Authors: Alexis J Lomakin, Kun Chun Lee, Sangyoon J Han, Duyen Amy Bui, Michael W Davidson, Alex Mogilner, Gaudenz DanuserAbstract:Symmetry-breaking polarization enables functional plasticity of Cells and tissues and is yet not well understood. Here we show that epithelial Cells, hard-wired to maintain a static morphology and to preserve tissue organization, can spontaneously switch to a migratory polarized phenotype after relaxation of the actomyosin cytoskeleton. We find that myosin II engages actin in the formation of cortical actomyosin bundles and thus makes it unavailable for deployment in the process of dendritic growth normally driving Cell motility. Under low-contractility regimes, epithelial Cells polarize in a front-back manner owing to the emergence of actin retrograde flows powered by dendritic polymerization of actin. Coupled to Cell movement, the flows transport myosin II from the front to the back of the Cell, where the motor locally 'locks' actin in contractile bundles. This polarization mechanism could be employed by embryonic and cancer epithelial Cells in microenvironments where high-contractility-driven Cell Motion is inefficient.
Andrea Münsterberg - One of the best experts on this subject based on the ideXlab platform.
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4d imaging reveals stage dependent random and directed Cell Motion during somite morphogenesis
Scientific Reports, 2018Co-Authors: James Mccoll, Gi Fay Mok, Anna Lippert, Aleks Ponjavic, Leila Muresan, Andrea MünsterbergAbstract:Somites are paired embryonic segments that form in a regular sequence from unsegmented mesoderm during vertebrate development. Although transient structures they are of fundamental importance as they generate Cell lineages of the musculoskeletal system in the trunk such as cartilage, tendon, bone, endothelial Cells and skeletal muscle. Surprisingly, very little is known about Cellular dynamics underlying the morphological transitions during somite differentiation. Here, we address this by examining Cellular rearrangements and morphogenesis in differentiating somites using live multi-photon imaging of transgenic chick embryos, where all Cells express a membrane-bound GFP. We specifically focussed on the dynamic Cellular changes in two principle regions within the somite, the medial and lateral domains, to investigate extensive morphological transformations. Furthermore, by using quantitative analysis and Cell tracking, we capture for the first time a directed movement of dermomyotomal progenitor Cells towards the rostro-medial domain of the dermomyotome, where skeletal muscle formation initiates.
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4d imaging reveals stage dependent random and directed Cell Motion during somite morphogenesis
bioRxiv, 2018Co-Authors: James Mccoll, Gi Fay Mok, Anna Lippert, Aleks Ponjavic, Leila Muresan, Andrea MünsterbergAbstract:Somites are paired embryonic segments that form in a regular sequence from unsegmented mesoderm during vertebrate development. Of fundamental importance, they are transient structures that generate Cell lineages of the musculoskeletal system in the trunk such as cartilage, tendon, bone, endothelial Cells and skeletal muscle. Surprisingly, very little is known about the morphological transition and Cellular dynamics during somite differentiation. Here, we address this by examining Cellular rearrangements and morphogenesis in differentiating somites using live multi photon imaging of GFP-transgenic chick embryos. We specifically focussed on the dynamic changes in two principle regions within the somite (the medial and lateral domains) to investigate extensive morphological changes. Furthermore, by using quantitative analysis and Cell tracking, we were able to capture for the first time a progenitor Cell bulk movement towards the rostral-medial domain of the myotome, where skeletal muscle formation first initiates.