72 results on '"Salbreux G"'
Search Results
2. 7.12 Biophysics of Cell Developmental Processes: A Lasercutter's Perspective
- Author
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Mayer, M., primary, Salbreux, G., additional, and Grill, S.W., additional
- Published
- 2012
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3. Spontaneous shear flow in confined cellular nematics
- Author
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Duclos, G., primary, Blanch-Mercader, C., additional, Yashunsky, V., additional, Salbreux, G., additional, Joanny, J.-F., additional, Prost, J., additional, and Silberzan, P., additional
- Published
- 2018
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4. Optimal chemotaxis in intermittent migration of animal cells
- Author
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Romanczuk, P., primary and Salbreux, G., additional
- Published
- 2015
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5. Impact of heating on passive and active biomechanics of suspended cells
- Author
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Chan, C. J., primary, Whyte, G., additional, Boyde, L., additional, Salbreux, G., additional, and Guck, J., additional
- Published
- 2014
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6. Hydrodynamics of Cellular Cortical Flows and the Formation of Contractile Rings
- Author
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Salbreux, G., primary, Prost, J., additional, and Joanny, J. F., additional
- Published
- 2009
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7. Shape oscillations of non-adhering fibroblast cells
- Author
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Salbreux, G, primary, Joanny, J F, additional, Prost, J, additional, and Pullarkat, P, additional
- Published
- 2007
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8. The Drosophila ecdysone receptor promotes or suppresses proliferation according to ligand level.
- Author
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Perez-Mockus G, Cocconi L, Alexandre C, Aerne B, Salbreux G, and Vincent JP
- Subjects
- Animals, Drosophila genetics, Ligands, Hormones, Cell Proliferation, Ecdysone, Drosophila Proteins genetics, Receptors, Steroid genetics
- Abstract
The steroid hormone 20-hydroxy-ecdysone (20E) promotes proliferation in Drosophila wing precursors at low titer but triggers proliferation arrest at high doses. Remarkably, wing precursors proliferate normally in the complete absence of the 20E receptor, suggesting that low-level 20E promotes proliferation by overriding the default anti-proliferative activity of the receptor. By contrast, 20E needs its receptor to arrest proliferation. Dose-response RNA sequencing (RNA-seq) analysis of ex vivo cultured wing precursors identifies genes that are quantitatively activated by 20E across the physiological range, likely comprising positive modulators of proliferation and other genes that are only activated at high doses. We suggest that some of these "high-threshold" genes dominantly suppress the activity of the pro-proliferation genes. We then show mathematically and with synthetic reporters that combinations of basic regulatory elements can recapitulate the behavior of both types of target genes. Thus, a relatively simple genetic circuit can account for the bimodal activity of this hormone., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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9. Active mesh and neural network pipeline for cell aggregate segmentation.
- Author
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Smith MB, Sparks H, Almagro J, Chaigne A, Behrens A, Dunsby C, and Salbreux G
- Subjects
- Animals, Mice, Microscopy, Fluorescence methods, Image Processing, Computer-Assisted methods, Neural Networks, Computer, Cell Nucleus
- Abstract
Segmenting cells within cellular aggregates in 3D is a growing challenge in cell biology due to improvements in capacity and accuracy of microscopy techniques. Here, we describe a pipeline to segment images of cell aggregates in 3D. The pipeline combines neural network segmentations with active meshes. We apply our segmentation method to cultured mouse mammary gland organoids imaged over 24 h with oblique plane microscopy, a high-throughput light-sheet fluorescence microscopy technique. We show that our method can also be applied to images of mouse embryonic stem cells imaged with a spinning disc microscope. We segment individual cells based on nuclei and cell membrane fluorescent markers, and track cells over time. We describe metrics to quantify the quality of the automated segmentation. Our segmentation pipeline involves a Fiji plugin that implements active mesh deformation and allows a user to create training data, automatically obtain segmentation meshes from original image data or neural network prediction, and manually curate segmentation data to identify and correct mistakes. Our active meshes-based approach facilitates segmentation postprocessing, correction, and integration with neural network prediction., Competing Interests: Declaration of interests C.D. has filed a patent application on dual-view oblique plane microscopy and has a licensed granted patent on oblique plane microscopy., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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10. Active morphogenesis of patterned epithelial shells.
- Author
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Khoromskaia D and Salbreux G
- Subjects
- Morphogenesis, Epithelium, Embryonic Development, Models, Biological, Epithelial Cells
- Abstract
Shape transformations of epithelial tissues in three dimensions, which are crucial for embryonic development or in vitro organoid growth, can result from active forces generated within the cytoskeleton of the epithelial cells. How the interplay of local differential tensions with tissue geometry and with external forces results in tissue-scale morphogenesis remains an open question. Here, we describe epithelial sheets as active viscoelastic surfaces and study their deformation under patterned internal tensions and bending moments. In addition to isotropic effects, we take into account nematic alignment in the plane of the tissue, which gives rise to shape-dependent, anisotropic active tensions and bending moments. We present phase diagrams of the mechanical equilibrium shapes of pre-patterned closed shells and explore their dynamical deformations. Our results show that a combination of nematic alignment and gradients in internal tensions and bending moments is sufficient to reproduce basic building blocks of epithelial morphogenesis, including fold formation, budding, neck formation, flattening, and tubulation., Competing Interests: DK, GS No competing interests declared, (© 2023, Khoromskaia and Salbreux.)
- Published
- 2023
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11. Interacting active surfaces: A model for three-dimensional cell aggregates.
- Author
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Torres-Sánchez A, Kerr Winter M, and Salbreux G
- Subjects
- Morphogenesis, Computer Simulation, Viscosity, Models, Biological, Myosins
- Abstract
We introduce a modelling and simulation framework for cell aggregates in three dimensions based on interacting active surfaces. Cell mechanics is captured by a physical description of the acto-myosin cortex that includes cortical flows, viscous forces, active tensions, and bending moments. Cells interact with each other via short-range forces capturing the effect of adhesion molecules. We discretise the model equations using a finite element method, and provide a parallel implementation in C++. We discuss examples of application of this framework to small and medium-sized aggregates: we consider the shape and dynamics of a cell doublet, a planar cell sheet, and a growing cell aggregate. This framework opens the door to the systematic exploration of the cell to tissue-scale mechanics of cell aggregates, which plays a key role in the morphogenesis of embryos and organoids., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Torres-Sánchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2022
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12. Pulsations and flows in tissues as two collective dynamics with simple cellular rules.
- Author
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Thiagarajan R, Bhat A, Salbreux G, Inamdar MM, and Riveline D
- Abstract
Collective motions of epithelial cells are essential for morphogenesis. Tissues elongate, contract, flow, and oscillate, thus sculpting embryos. These tissue level dynamics are known, but the physical mechanisms at the cellular level are unclear. Here, we demonstrate that a single epithelial monolayer of MDCK cells can exhibit two types of local tissue kinematics, pulsations and long range coherent flows, characterized by using quantitative live imaging. We report that these motions can be controlled with internal and external cues such as specific inhibitors and substrate friction modulation. We demonstrate the associated mechanisms with a unified vertex model. When cell velocity alignment and random diffusion of cell polarization are comparable, a pulsatile flow emerges whereas tissue undergoes long-range flows when velocity alignment dominates which is consistent with cytoskeletal dynamics measurements. We propose that environmental friction, acto-myosin distributions, and cell polarization kinetics are important in regulating dynamics of tissue morphogenesis., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)
- Published
- 2022
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13. Spindle reorientation in response to mechanical stress is an emergent property of the spindle positioning mechanisms.
- Author
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Kelkar M, Bohec P, Smith MB, Sreenivasan V, Lisica A, Valon L, Ferber E, Baum B, Salbreux G, and Charras G
- Subjects
- Actomyosin metabolism, Computer Simulation, Cytoplasm, Optogenetics, rhoA GTP-Binding Protein metabolism, Microtubules metabolism, Spindle Apparatus physiology, Stress, Mechanical
- Abstract
Proper orientation of the mitotic spindle plays a crucial role in embryos, during tissue development, and in adults, where it functions to dissipate mechanical stress to maintain tissue integrity and homeostasis. While mitotic spindles have been shown to reorient in response to external mechanical stresses, the subcellular cues that mediate spindle reorientation remain unclear. Here, we used a combination of optogenetics and computational modeling to investigate how mitotic spindles respond to inhomogeneous tension within the actomyosin cortex. Strikingly, we found that the optogenetic activation of RhoA only influences spindle orientation when it is induced at both poles of the cell. Under these conditions, the sudden local increase in cortical tension induced by RhoA activation reduces pulling forces exerted by cortical regulators on astral microtubules. This leads to a perturbation of the balance of torques exerted on the spindle, which causes it to rotate. Thus, spindle rotation in response to mechanical stress is an emergent phenomenon arising from the interaction between the spindle positioning machinery and the cell cortex.
- Published
- 2022
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14. Mechanical constraints to cell-cycle progression in a pseudostratified epithelium.
- Author
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Hecht S, Perez-Mockus G, Schienstock D, Recasens-Alvarez C, Merino-Aceituno S, Smith M, Salbreux G, Degond P, and Vincent JP
- Subjects
- Cell Cycle, Cell Nucleus metabolism, Epithelium metabolism, Mechanotransduction, Cellular, Mitosis
- Abstract
As organs and tissues approach their normal size during development or regeneration, growth slows down, and cell proliferation progressively comes to a halt. Among the various processes suggested to contribute to growth termination,
1-10 mechanical feedback, perhaps via adherens junctions, has been suggested to play a role.11-14 However, since adherens junctions are only present in a narrow plane of the subapical region, other structures are likely needed to sense mechanical stresses along the apical-basal (A-B) axis, especially in a thick pseudostratified epithelium. This could be achieved by nuclei, which have been implicated in mechanotransduction in tissue culture.15 In addition, mechanical constraints imposed by nuclear crowding and spatial confinement could affect interkinetic nuclear migration (IKNM),16 which allows G2 nuclei to reach the apical surface, where they normally undergo mitosis.17-25 To explore how mechanical constraints affect IKNM, we devised an individual-based model that treats nuclei as deformable objects constrained by the cell cortex and the presence of other nuclei. The model predicts changes in the proportion of cell-cycle phases during growth, which we validate with the cell-cycle phase reporter FUCCI (Fluorescent Ubiquitination-based Cell Cycle Indicator).26 However, this model does not preclude indefinite growth, leading us to postulate that nuclei must migrate basally to access a putative basal signal required for S phase entry. With this refinement, our updated model accounts for the observed progressive slowing down of growth and explains how pseudostratified epithelia reach a stereotypical thickness upon completion of growth., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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15. Scaling of entropy production under coarse graining in active disordered media.
- Author
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Cocconi L, Salbreux G, and Pruessner G
- Abstract
Entropy production plays a fundamental role in the study of nonequilibrium systems by offering a quantitative handle on the degree of time-reversal symmetry breaking. It depends crucially on the degree of freedom considered as well as on the scale of description. How the entropy production at one resolution of the degrees of freedom is related to the entropy production at another resolution is a fundamental question which has recently attracted interest. This relationship is of particular relevance to coarse-grained and continuum descriptions of a given phenomenon. In this work, we derive the scaling of the entropy production under iterative coarse graining on the basis of the correlations of the underlying microscopic transition rates for noninteracting particles in active disordered media. Our approach unveils a natural criterion to distinguish equilibrium-like and genuinely nonequilibrium macroscopic phenomena based on the sign of the scaling exponent of the entropy production per mesostate.
- Published
- 2022
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16. ECM degradation in the Drosophila abdominal epidermis initiates tissue growth that ceases with rapid cell-cycle exit.
- Author
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Davis JR, Ainslie AP, Williamson JJ, Ferreira A, Torres-Sánchez A, Hoppe A, Mangione F, Smith MB, Martin-Blanco E, Salbreux G, and Tapon N
- Subjects
- Animals, Cell Cycle, Cell Division, Epidermis, Mice, Drosophila, Epidermal Cells
- Abstract
During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
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17. Tissue hydraulics: Physics of lumen formation and interaction.
- Author
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Torres-Sánchez A, Kerr Winter M, and Salbreux G
- Subjects
- Extracellular Fluid, Morphogenesis, Osmosis, Cytoskeleton, Physics
- Abstract
Lumen formation plays an essential role in the morphogenesis of tissues during development. Here we review the physical principles that play a role in the growth and coarsening of lumens. Solute pumping by the cell, hydraulic flows driven by differences of osmotic and hydrostatic pressures, balance of forces between extracellular fluids and cell-generated cytoskeletal forces, and electro-osmotic effects have been implicated in determining the dynamics and steady-state of lumens. We use the framework of linear irreversible thermodynamics to discuss the relevant force, time and length scales involved in these processes. We focus on order of magnitude estimates of physical parameters controlling lumen formation and coarsening., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
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18. Special rebranding issue: "Quantitative cell and developmental biology".
- Author
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Heisenberg CP, Lennon AM, Mayor R, and Salbreux G
- Subjects
- Developmental Biology
- Published
- 2021
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19. Epithelial colonies in vitro elongate through collective effects.
- Author
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Comelles J, Ss S, Lu L, Le Maout E, Anvitha S, Salbreux G, Jülicher F, Inamdar MM, and Riveline D
- Subjects
- Animals, Biomechanical Phenomena, Caco-2 Cells, Dogs, Humans, Madin Darby Canine Kidney Cells, Cell Division, Epithelial Cells cytology, Epithelium embryology, Morphogenesis
- Abstract
Epithelial tissues of the developing embryos elongate by different mechanisms, such as neighbor exchange, cell elongation, and oriented cell division. Since autonomous tissue self-organization is influenced by external cues such as morphogen gradients or neighboring tissues, it is difficult to distinguish intrinsic from directed tissue behavior. The mesoscopic processes leading to the different mechanisms remain elusive. Here, we study the spontaneous elongation behavior of spreading circular epithelial colonies in vitro. By quantifying deformation kinematics at multiple scales, we report that global elongation happens primarily due to cell elongations, and its direction correlates with the anisotropy of the average cell elongation. By imposing an external time-periodic stretch, the axis of this global symmetry breaking can be modified and elongation occurs primarily due to orientated neighbor exchange. These different behaviors are confirmed using a vertex model for collective cell behavior, providing a framework for understanding autonomous tissue elongation and its origins., Competing Interests: JC, SS, LL, EL, SA, GS, FJ, MI, DR No competing interests declared, (© 2021, Comelles et al.)
- Published
- 2021
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20. Dual-view oblique plane microscopy (dOPM).
- Author
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Sparks H, Dent L, Bakal C, Behrens A, Salbreux G, and Dunsby C
- Abstract
We present a new folded dual-view oblique plane microscopy (OPM) technique termed dOPM that enables two orthogonal views of the sample to be obtained by translating a pair of tilted mirrors in refocussing space. Using a water immersion 40× 1.15 NA primary objective, deconvolved image volumes of 200 nm beads were measured to have full width at half maxima (FWHM) of 0.35 ± 0.04 µm and 0.39 ± 0.02 µm laterally and 0.81 ± 0.07 µm axially. The measured z-sectioning value was 1.33 ± 0.45 µm using light-sheet FWHM in the frames of the two views of 4.99 ± 0.58 µm and 4.89 ± 0.63 µm. To qualitatively demonstrate that the system can reduce shadow artefacts while providing a more isotropic resolution, a multi-cellular spheroid approximately 100 µm in diameter was imaged., Competing Interests: CD has filed a patent application on dOPM and has a licensed granted patent on OPM., (Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)
- Published
- 2020
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21. Patterning and growth control in vivo by an engineered GFP gradient.
- Author
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Stapornwongkul KS, de Gennes M, Cocconi L, Salbreux G, and Vincent JP
- Subjects
- Animals, Drosophila Proteins genetics, Drosophila Proteins metabolism, Glycosylphosphatidylinositols metabolism, Green Fluorescent Proteins genetics, Imaginal Discs growth & development, Protein Engineering, Recombinant Fusion Proteins genetics, Wings, Animal growth & development, Body Patterning, Drosophila melanogaster growth & development, Green Fluorescent Proteins metabolism, Recombinant Fusion Proteins metabolism
- Abstract
Morphogen gradients provide positional information during development. To uncover the minimal requirements for morphogen gradient formation, we have engineered a synthetic morphogen in Drosophila wing primordia. We show that an inert protein, green fluorescent protein (GFP), can form a detectable diffusion-based gradient in the presence of surface-associated anti-GFP nanobodies, which modulate the gradient by trapping the ligand and limiting leakage from the tissue. We next fused anti-GFP nanobodies to the receptors of Dpp, a natural morphogen, to render them responsive to extracellular GFP. In the presence of these engineered receptors, GFP could replace Dpp to organize patterning and growth in vivo. Concomitant expression of glycosylphosphatidylinositol (GPI)-anchored nonsignaling receptors further improved patterning, to near-wild-type quality. Theoretical arguments suggest that GPI anchorage could be important for these receptors to expand the gradient length scale while at the same time reducing leakage., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2020
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22. Mechanochemical Crosstalk Produces Cell-Intrinsic Patterning of the Cortex to Orient the Mitotic Spindle.
- Author
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Dimitracopoulos A, Srivastava P, Chaigne A, Win Z, Shlomovitz R, Lancaster OM, Le Berre M, Piel M, Franze K, Salbreux G, and Baum B
- Subjects
- HeLa Cells, Humans, Signal Transduction, Dyneins physiology, Mechanotransduction, Cellular, Microtubules physiology, Mitosis, Spindle Apparatus physiology
- Abstract
Proliferating animal cells are able to orient their mitotic spindles along their interphase cell axis, setting up the axis of cell division, despite rounding up as they enter mitosis. This has previously been attributed to molecular memory and, more specifically, to the maintenance of adhesions and retraction fibers in mitosis [1-6], which are thought to act as local cues that pattern cortical Gαi, LGN, and nuclear mitotic apparatus protein (NuMA) [3, 7-18]. This cortical machinery then recruits and activates Dynein motors, which pull on astral microtubules to position the mitotic spindle. Here, we reveal a dynamic two-way crosstalk between the spindle and cortical motor complexes that depends on a Ran-guanosine triphosphate (GTP) signal [12], which is sufficient to drive continuous monopolar spindle motion independently of adhesive cues in flattened human cells in culture. Building on previous work [1, 12, 19-23], we implemented a physical model of the system that recapitulates the observed spindle-cortex interactions. Strikingly, when this model was used to study spindle dynamics in cells entering mitosis, the chromatin-based signal was found to preferentially clear force generators from the short cell axis, so that cortical motors pulling on astral microtubules align bipolar spindles with the interphase long cell axis, without requiring a fixed cue or a physical memory of interphase shape. Thus, our analysis shows that the ability of chromatin to pattern the cortex during the process of mitotic rounding is sufficient to translate interphase shape into a cortical pattern that can be read by the spindle, which then guides the axis of cell division., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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23. In Vivo Force Application Reveals a Fast Tissue Softening and External Friction Increase during Early Embryogenesis.
- Author
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D'Angelo A, Dierkes K, Carolis C, Salbreux G, and Solon J
- Subjects
- Animals, Biomechanical Phenomena, Cytoskeleton metabolism, Drosophila melanogaster embryology, Embryo, Nonmammalian embryology, Embryonic Development
- Abstract
During development, cell-generated forces induce tissue-scale deformations to shape the organism [1,2]. The pattern and extent of these deformations depend not solely on the temporal and spatial profile of the generated force fields but also on the mechanical properties of the tissues that the forces act on. It is thus conceivable that, much like the cell-generated forces, the mechanical properties of tissues are modulated during development in order to drive morphogenesis toward specific developmental endpoints. Although many approaches have recently emerged to assess effective mechanical parameters of tissues [3-8], they could not quantitatively relate spatially localized force induction to tissue-scale deformations in vivo. Here, we present a method that overcomes this limitation. Our approach is based on the application of controlled forces on a single microparticle embedded in an individual cell of an embryo. Combining measurements of bead displacement with the analysis of induced deformation fields in a continuum mechanics framework, we quantify material properties of the tissue and follow their changes over time. In particular, we uncover a rapid change in tissue response occurring during Drosophila cellularization, resulting from a softening of the blastoderm and an increase of external friction. We find that the microtubule cytoskeleton is a major contributor to epithelial mechanics at this stage. We identify developmentally controlled modulations in perivitelline spacing that can account for the changes in friction. Overall, our method allows for the measurement of key mechanical parameters governing tissue-scale deformations and flows occurring during morphogenesis., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
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24. Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling.
- Author
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Petridou NI, Grigolon S, Salbreux G, Hannezo E, and Heisenberg CP
- Subjects
- Animals, Animals, Genetically Modified, Biomechanical Phenomena, Blastoderm cytology, Cell Communication physiology, Cell Division, Cell Movement physiology, Elasticity, Embryo, Nonmammalian cytology, Embryo, Nonmammalian embryology, Mitosis physiology, Viscosity, Zebrafish genetics, Blastoderm embryology, Morphogenesis, Wnt Signaling Pathway physiology, Zebrafish embryology
- Abstract
Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cell-cell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis.
- Published
- 2019
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25. Tissue curvature and apicobasal mechanical tension imbalance instruct cancer morphogenesis.
- Author
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Messal HA, Alt S, Ferreira RMM, Gribben C, Wang VM, Cotoi CG, Salbreux G, and Behrens A
- Subjects
- Animals, Humans, Mice, Organoids pathology, Stress, Mechanical, Biomechanical Phenomena, Cell Polarity, Cell Transformation, Neoplastic, Morphogenesis, Pancreatic Ducts pathology, Pancreatic Neoplasms pathology
- Abstract
Tubular epithelia are a basic building block of organs and a common site of cancer occurrence
1-4 . During tumorigenesis, transformed cells overproliferate and epithelial architecture is disrupted. However, the biophysical parameters that underlie the adoption of abnormal tumour tissue shapes are unknown. Here we show in the pancreas of mice that the morphology of epithelial tumours is determined by the interplay of cytoskeletal changes in transformed cells and the existing tubular geometry. To analyse the morphological changes in tissue architecture during the initiation of cancer, we developed a three-dimensional whole-organ imaging technique that enables tissue analysis at single-cell resolution. Oncogenic transformation of pancreatic ducts led to two types of neoplastic growth: exophytic lesions that expanded outwards from the duct and endophytic lesions that grew inwards to the ductal lumen. Myosin activity was higher apically than basally in wild-type cells, but upon transformation this gradient was lost in both lesion types. Three-dimensional vertex model simulations and a continuum theory of epithelial mechanics, which incorporate the cytoskeletal changes observed in transformed cells, indicated that the diameter of the source epithelium instructs the morphology of growing tumours. Three-dimensional imaging revealed that-consistent with theory predictions-small pancreatic ducts produced exophytic growth, whereas large ducts deformed endophytically. Similar patterns of lesion growth were observed in tubular epithelia of the liver and lung; this finding identifies tension imbalance and tissue curvature as fundamental determinants of epithelial tumorigenesis.- Published
- 2019
- Full Text
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26. Stability and Roughness of Interfaces in Mechanically Regulated Tissues.
- Author
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Williamson JJ and Salbreux G
- Subjects
- Cell Physiological Phenomena, Friction, Humans, Surface Properties, Cell Movement, Computer Simulation, Models, Molecular, Stress, Mechanical
- Abstract
Cell division and death can be regulated by the mechanical forces within a tissue. We study the consequences for the stability and roughness of a propagating interface by analyzing a model of mechanically regulated tissue growth in the regime of small driving forces. For an interface driven by homeostatic pressure imbalance or leader-cell motility, long and intermediate-wavelength instabilities arise, depending, respectively, on an effective viscosity of cell number change, and on substrate friction. A further mechanism depends on the strength of directed motility forces acting in the bulk. We analyze the fluctuations of a stable interface subjected to cell-level stochasticity, and find that mechanical feedback can help preserve reproducibility at the tissue scale. Our results elucidate mechanisms that could be important for orderly interface motion in developing tissues.
- Published
- 2018
- Full Text
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27. Adherens Junction Length during Tissue Contraction Is Controlled by the Mechanosensitive Activity of Actomyosin and Junctional Recycling.
- Author
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Sumi A, Hayes P, D'Angelo A, Colombelli J, Salbreux G, Dierkes K, and Solon J
- Subjects
- Animals, Cadherins metabolism, Drosophila Proteins metabolism, Drosophila melanogaster cytology, Endocytosis physiology, Actin Cytoskeleton metabolism, Actomyosin metabolism, Adherens Junctions physiology, Morphogenesis physiology
- Abstract
During epithelial contraction, cells generate forces to constrict their surface and, concurrently, fine-tune the length of their adherens junctions to ensure force transmission. While many studies have focused on understanding force generation, little is known on how junctional length is controlled. Here, we show that, during amnioserosa contraction in Drosophila dorsal closure, adherens junctions reduce their length in coordination with the shrinkage of apical cell area, maintaining a nearly constant junctional straightness. We reveal that junctional straightness and integrity depend on the endocytic machinery and on the mechanosensitive activity of the actomyosin cytoskeleton. On one hand, upon junctional stretch and decrease in E-cadherin density, actomyosin relocalizes from the medial area to the junctions, thus maintaining junctional integrity. On the other hand, when junctions have excess material and ruffles, junction removal is enhanced, and high junctional straightness and tension are restored. These two mechanisms control junctional length and integrity during morphogenesis., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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28. Differential lateral and basal tension drive folding of Drosophila wing discs through two distinct mechanisms.
- Author
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Sui L, Alt S, Weigert M, Dye N, Eaton S, Jug F, Myers EW, Jülicher F, Salbreux G, and Dahmann C
- Subjects
- Actins metabolism, Actomyosin, Amides antagonists & inhibitors, Animals, Biomechanical Phenomena, Body Patterning genetics, Cell Division, Cell Proliferation, Cell Shape, Cell Size, Drosophila anatomy & histology, Drosophila embryology, Drosophila genetics, Drosophila Proteins genetics, Drosophila Proteins metabolism, Epithelial Cells drug effects, Epithelium drug effects, Extracellular Matrix, Imaginal Discs growth & development, Larva cytology, Larva metabolism, Laser Therapy, Models, Anatomic, Models, Biological, Pyridines antagonists & inhibitors, Drosophila growth & development, Epithelial Cells cytology, Epithelium anatomy & histology, Epithelium embryology, Morphogenesis, Stress, Mechanical
- Abstract
Epithelial folding transforms simple sheets of cells into complex three-dimensional tissues and organs during animal development. Epithelial folding has mainly been attributed to mechanical forces generated by an apically localized actomyosin network, however, contributions of forces generated at basal and lateral cell surfaces remain largely unknown. Here we show that a local decrease of basal tension and an increased lateral tension, but not apical constriction, drive the formation of two neighboring folds in developing Drosophila wing imaginal discs. Spatially defined reduction of extracellular matrix density results in local decrease of basal tension in the first fold; fluctuations in F-actin lead to increased lateral tension in the second fold. Simulations using a 3D vertex model show that the two distinct mechanisms can drive epithelial folding. Our combination of lateral and basal tension measurements with a mechanical tissue model reveals how simple modulations of surface and edge tension drive complex three-dimensional morphological changes.
- Published
- 2018
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29. A non-cell-autonomous actin redistribution enables isotropic retinal growth.
- Author
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Matejčić M, Salbreux G, and Norden C
- Subjects
- Actins physiology, Animals, Cell Growth Processes physiology, Cell Movement, Cell Shape physiology, Morphogenesis, Zebrafish, Zebrafish Proteins, Retina cytology, Retina growth & development
- Abstract
Tissue shape is often established early in development and needs to be scaled isotropically during growth. However, the cellular contributors and ways by which cells interact tissue-wide to enable coordinated isotropic tissue scaling are not yet understood. Here, we follow cell and tissue shape changes in the zebrafish retinal neuroepithelium, which forms a cup with a smooth surface early in development and maintains this architecture as it grows. By combining 3D analysis and theory, we show how a global increase in cell height can maintain tissue shape during growth. Timely cell height increase occurs concurrently with a non-cell-autonomous actin redistribution. Blocking actin redistribution and cell height increase perturbs isotropic scaling and leads to disturbed, folded tissue shape. Taken together, our data show how global changes in cell shape enable isotropic growth of the developing retinal neuroepithelium, a concept that could also apply to other systems., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
30. Developmental Biology: Morphogen in a Dish.
- Author
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Stapornwongkul KS, Salbreux G, and Vincent JP
- Subjects
- Developmental Biology, Hedgehog Proteins, Signal Transduction
- Abstract
Reconstitution of a Hedgehog morphogen gradient in vitro and in silico reveals the architectural features of the signal transduction pathway that ensure rapid formation of a robust signalling gradient., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
31. Apical and Basal Matrix Remodeling Control Epithelial Morphogenesis.
- Author
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Diaz-de-la-Loza MD, Ray RP, Ganguly PS, Alt S, Davis JR, Hoppe A, Tapon N, Salbreux G, and Thompson BJ
- Subjects
- Animals, Cell Polarity physiology, Cell Shape physiology, Drosophila Proteins metabolism, Drosophila melanogaster cytology, Embryo, Nonmammalian embryology, Epithelium metabolism, Matrix Metalloproteinase 1 metabolism, Matrix Metalloproteinase 2 metabolism, Membrane Proteins metabolism, Myosin Type II metabolism, Serine Endopeptidases metabolism, Body Patterning physiology, Drosophila melanogaster embryology, Epithelial Cells cytology, Lower Extremity embryology, Morphogenesis physiology, Wings, Animal embryology
- Abstract
Epithelial tissues can elongate in two dimensions by polarized cell intercalation, oriented cell division, or cell shape change, owing to local or global actomyosin contractile forces acting in the plane of the tissue. In addition, epithelia can undergo morphogenetic change in three dimensions. We show that elongation of the wings and legs of Drosophila involves a columnar-to-cuboidal cell shape change that reduces cell height and expands cell width. Remodeling of the apical extracellular matrix by the Stubble protease and basal matrix by MMP1/2 proteases induces wing and leg elongation. Matrix remodeling does not occur in the haltere, a limb that fails to elongate. Limb elongation is made anisotropic by planar polarized Myosin-II, which drives convergent extension along the proximal-distal axis. Subsequently, Myosin-II relocalizes to lateral membranes to accelerate columnar-to-cuboidal transition and isotropic tissue expansion. Thus, matrix remodeling induces dynamic changes in actomyosin contractility to drive epithelial morphogenesis in three dimensions., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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32. Hydrodynamic theory of active matter.
- Author
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Jülicher F, Grill SW, and Salbreux G
- Abstract
We review the general hydrodynamic theory of active soft materials that is motivated in particular by biological matter. We present basic concepts of irreversible thermodynamics of spatially extended multicomponent active systems. Starting from the rate of entropy production, we identify conjugate thermodynamic fluxes and forces and present generic constitutive equations of polar active fluids and active gels. We also discuss angular momentum conservation which plays a role in the the physics of active chiral gels. The irreversible thermodynamics of active gels provides a general framework to discuss the physics that underlies a wide variety of biological processes in cells and in multicellular tissues.
- Published
- 2018
- Full Text
- View/download PDF
33. Myosin II Controls Junction Fluctuations to Guide Epithelial Tissue Ordering.
- Author
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Curran S, Strandkvist C, Bathmann J, de Gennes M, Kabla A, Salbreux G, and Baum B
- Subjects
- Actomyosin metabolism, Animals, Cadherins metabolism, Adherens Junctions physiology, Drosophila Proteins metabolism, Drosophila melanogaster metabolism, Epithelium metabolism, Myosin Type II metabolism
- Abstract
Under conditions of homeostasis, dynamic changes in the length of individual adherens junctions (AJs) provide epithelia with the fluidity required to maintain tissue integrity in the face of intrinsic and extrinsic forces. While the contribution of AJ remodeling to developmental morphogenesis has been intensively studied, less is known about AJ dynamics in other circumstances. Here, we study AJ dynamics in an epithelium that undergoes a gradual increase in packing order, without concomitant large-scale changes in tissue size or shape. We find that neighbor exchange events are driven by stochastic fluctuations in junction length, regulated in part by junctional actomyosin. In this context, the developmental increase of isotropic junctional actomyosin reduces the rate of neighbor exchange, contributing to tissue order. We propose a model in which the local variance in tension between junctions determines whether actomyosin-based forces will inhibit or drive the topological transitions that either refine or deform a tissue., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2017
- Full Text
- View/download PDF
34. Mechanics of active surfaces.
- Author
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Salbreux G and Jülicher F
- Subjects
- Elasticity, Rotation, Torque, Models, Theoretical, Surface Properties
- Abstract
We derive a fully covariant theory of the mechanics of active surfaces. This theory provides a framework for the study of active biological or chemical processes at surfaces, such as the cell cortex, the mechanics of epithelial tissues, or reconstituted active systems on surfaces. We introduce forces and torques acting on a surface, and derive the associated force balance conditions. We show that surfaces with in-plane rotational symmetry can have broken up-down, chiral, or planar-chiral symmetry. We discuss the rate of entropy production in the surface and write linear constitutive relations that satisfy the Onsager relations. We show that the bending modulus, the spontaneous curvature, and the surface tension of a passive surface are renormalized by active terms. Finally, we identify active terms which are not found in a passive theory and discuss examples of shape instabilities that are related to active processes in the surface.
- Published
- 2017
- Full Text
- View/download PDF
35. Actin cortex architecture regulates cell surface tension.
- Author
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Chugh P, Clark AG, Smith MB, Cassani DAD, Dierkes K, Ragab A, Roux PP, Charras G, Salbreux G, and Paluch EK
- Subjects
- Actin Cytoskeleton ultrastructure, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, CapZ Actin Capping Protein genetics, CapZ Actin Capping Protein metabolism, Cofilin 1 genetics, Cofilin 1 metabolism, Computer Simulation, Formins, HeLa Cells, Humans, Interphase, Mitosis, Models, Biological, Surface Tension, Transfection, Actin Cytoskeleton metabolism, Actins metabolism, Cell Cycle, Cell Shape, Mechanotransduction, Cellular
- Abstract
Animal cell shape is largely determined by the cortex, a thin actin network underlying the plasma membrane in which myosin-driven stresses generate contractile tension. Tension gradients result in local contractions and drive cell deformations. Previous cortical tension regulation studies have focused on myosin motors. Here, we show that cortical actin network architecture is equally important. First, we observe that actin cortex thickness and tension are inversely correlated during cell-cycle progression. We then show that the actin filament length regulators CFL1, CAPZB and DIAPH1 regulate mitotic cortex thickness and find that both increasing and decreasing thickness decreases tension in mitosis. This suggests that the mitotic cortex is poised close to a tension maximum. Finally, using a computational model, we identify a physical mechanism by which maximum tension is achieved at intermediate actin filament lengths. Our results indicate that actin network architecture, alongside myosin activity, is key to cell surface tension regulation.
- Published
- 2017
- Full Text
- View/download PDF
36. Vertex models: from cell mechanics to tissue morphogenesis.
- Author
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Alt S, Ganguly P, and Salbreux G
- Subjects
- Animals, Cell Differentiation, Cell Shape, Epidermal Cells, Epithelial Cells physiology, Humans, Models, Biological, Morphogenesis, Epidermis growth & development, Epithelial Cells cytology
- Abstract
Tissue morphogenesis requires the collective, coordinated motion and deformation of a large number of cells. Vertex model simulations for tissue mechanics have been developed to bridge the scales between force generation at the cellular level and tissue deformation and flows. We review here various formulations of vertex models that have been proposed for describing tissues in two and three dimensions. We discuss a generic formulation using a virtual work differential, and we review applications of vertex models to biological morphogenetic processes. We also highlight recent efforts to obtain continuum theories of tissue mechanics, which are effective, coarse-grained descriptions of vertex models.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'., (© 2017 The Authors.)
- Published
- 2017
- Full Text
- View/download PDF
37. Friction forces position the neural anlage.
- Author
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Smutny M, Ákos Z, Grigolon S, Shamipour S, Ruprecht V, Čapek D, Behrndt M, Papusheva E, Tada M, Hof B, Vicsek T, Salbreux G, and Heisenberg CP
- Subjects
- Animals, Biomechanical Phenomena, Cadherins metabolism, Cell Communication, Cell Movement, Embryo, Nonmammalian cytology, Endoderm cytology, Endoderm embryology, Gastrulation, Hydrodynamics, Mesoderm cytology, Mesoderm embryology, Models, Biological, Morphogenesis, Mutation genetics, Neural Plate cytology, Neural Plate embryology, Zebrafish Proteins metabolism, Friction, Nervous System embryology, Zebrafish embryology
- Abstract
During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo.
- Published
- 2017
- Full Text
- View/download PDF
38. Triangles bridge the scales: Quantifying cellular contributions to tissue deformation.
- Author
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Merkel M, Etournay R, Popović M, Salbreux G, Eaton S, and Jülicher F
- Subjects
- Animals, Biomechanical Phenomena, Drosophila melanogaster, Wings, Animal cytology, Wings, Animal growth & development, Wings, Animal physiology, Cell Physiological Phenomena, Models, Biological
- Abstract
In this article, we propose a general framework to study the dynamics and topology of cellular networks that capture the geometry of cell packings in two-dimensional tissues. Such epithelia undergo large-scale deformation during morphogenesis of a multicellular organism. Large-scale deformations emerge from many individual cellular events such as cell shape changes, cell rearrangements, cell divisions, and cell extrusions. Using a triangle-based representation of cellular network geometry, we obtain an exact decomposition of large-scale material deformation. Interestingly, our approach reveals contributions of correlations between cellular rotations and elongation as well as cellular growth and elongation to tissue deformation. Using this triangle method, we discuss tissue remodeling in the developing pupal wing of the fly Drosophila melanogaster.
- Published
- 2017
- Full Text
- View/download PDF
39. The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation.
- Author
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Morita H, Grigolon S, Bock M, Krens SF, Salbreux G, and Heisenberg CP
- Subjects
- Animals, Blastoderm cytology, Blastoderm metabolism, Cell Communication, Cell Count, Cell Movement, Cell Proliferation, Computer Simulation, Embryo, Nonmammalian cytology, Stress, Physiological, Surface Tension, Biophysical Phenomena, Gastrulation, Morphogenesis, Zebrafish embryology, Zebrafish physiology
- Abstract
Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during "doming," when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
40. Cortical flow aligns actin filaments to form a furrow.
- Author
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Reymann AC, Staniscia F, Erzberger A, Salbreux G, and Grill SW
- Subjects
- Animals, Actomyosin metabolism, Caenorhabditis elegans physiology, Cytokinesis, Protein Multimerization, Zygote physiology
- Abstract
Cytokinesis in eukaryotic cells is often accompanied by actomyosin cortical flow. Over 30 years ago, Borisy and White proposed that cortical flow converging upon the cell equator compresses the actomyosin network to mechanically align actin filaments. However, actin filaments also align via search-and-capture, and to what extent compression by flow or active alignment drive furrow formation remains unclear. Here, we quantify the dynamical organization of actin filaments at the onset of ring assembly in the C. elegans zygote, and provide a framework for determining emergent actomyosin material parameters by the use of active nematic gel theory. We characterize flow-alignment coupling, and verify at a quantitative level that compression by flow drives ring formation. Finally, we find that active alignment enhances but is not required for ring formation. Our work characterizes the physical mechanisms of actomyosin ring formation and highlights the role of flow as a central organizer of actomyosin network architecture., Competing Interests: The authors declare that no competing interests exist.
- Published
- 2016
- Full Text
- View/download PDF
41. Steering cell migration by alternating blebs and actin-rich protrusions.
- Author
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Diz-Muñoz A, Romanczuk P, Yu W, Bergert M, Ivanovitch K, Salbreux G, Heisenberg CP, and Paluch EK
- Subjects
- Animals, Endoderm cytology, Mesoderm cytology, Morpholinos pharmacology, Pseudopodia drug effects, Stem Cells cytology, Stem Cells drug effects, Stem Cells metabolism, Actins metabolism, Cell Movement drug effects, Pseudopodia metabolism, Zebrafish metabolism
- Abstract
Background: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood., Results: Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision., Conclusions: Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.
- Published
- 2016
- Full Text
- View/download PDF
42. TissueMiner: A multiscale analysis toolkit to quantify how cellular processes create tissue dynamics.
- Author
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Etournay R, Merkel M, Popović M, Brandl H, Dye NA, Aigouy B, Salbreux G, Eaton S, and Jülicher F
- Subjects
- Animals, Drosophila physiology, Image Processing, Computer-Assisted methods, Time-Lapse Imaging, Computational Biology methods, Databases, Factual, Epithelium physiology, Morphogenesis
- Abstract
Segmentation and tracking of cells in long-term time-lapse experiments has emerged as a powerful method to understand how tissue shape changes emerge from the complex choreography of constituent cells. However, methods to store and interrogate the large datasets produced by these experiments are not widely available. Furthermore, recently developed methods for relating tissue shape changes to cell dynamics have not yet been widely applied by biologists because of their technical complexity. We therefore developed a database format that stores cellular connectivity and geometry information of deforming epithelial tissues, and computational tools to interrogate it and perform multi-scale analysis of morphogenesis. We provide tutorials for this computational framework, called TissueMiner, and demonstrate its capabilities by comparing cell and tissue dynamics in vein and inter-vein subregions of the Drosophila pupal wing. These analyses reveal an unexpected role for convergent extension in shaping wing veins.
- Published
- 2016
- Full Text
- View/download PDF
43. Role of Turnover in Active Stress Generation in a Filament Network.
- Author
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Hiraiwa T and Salbreux G
- Subjects
- Biomechanical Phenomena, Muscle Contraction, Computer Simulation, Cytoskeleton, Models, Biological, Molecular Motor Proteins
- Abstract
We study the effect of turnover of cross-linkers, motors, and filaments on the generation of a contractile stress in a network of filaments connected by passive cross-linkers and subjected to the forces exerted by molecular motors. We perform numerical simulations where filaments are treated as rigid rods and molecular motors move fast compared to the time scale of an exchange of cross-linkers. We show that molecular motors create a contractile stress above a critical number of cross-linkers. When passive cross-linkers are allowed to turn over, the stress exerted by the network vanishes due to the formation of clusters. When both filaments and passive cross-linkers turn over, clustering is prevented and the network reaches a dynamic contractile steady state. A maximum stress is reached for an optimum ratio of the filament and cross-linker turnover rates. Taken together, our work reveals conditions for stress generation by molecular motors in a fluid isotropic network of rearranging filaments.
- Published
- 2016
- Full Text
- View/download PDF
44. Shape remodeling and blebbing of active cytoskeletal vesicles.
- Author
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Loiseau E, Schneider JA, Keber FC, Pelzl C, Massiera G, Salbreux G, and Bausch AR
- Subjects
- Actins metabolism, Actomyosin chemistry, Biomimetics, Cell Membrane chemistry, Microtubules chemistry, Muscle Contraction physiology, Actin Cytoskeleton chemistry, Actins chemistry, Cytoskeleton chemistry, Molecular Motor Proteins chemistry
- Abstract
Morphological transformations of living cells, such as shape adaptation to external stimuli, blebbing, invagination, or tethering, result from an intricate interplay between the plasma membrane and its underlying cytoskeleton, where molecular motors generate forces. Cellular complexity defies a clear identification of the competing processes that lead to such a rich phenomenology. In a synthetic biology approach, designing a cell-like model assembled from a minimal set of purified building blocks would allow the control of all relevant parameters. We reconstruct actomyosin vesicles in which the coupling of the cytoskeleton to the membrane, the topology of the cytoskeletal network, and the contractile activity can all be precisely controlled and tuned. We demonstrate that tension generation of an encapsulated active actomyosin network suffices for global shape transformation of cell-sized lipid vesicles, which are reminiscent of morphological adaptations in living cells. The observed polymorphism of our cell-like model, such as blebbing, tether extrusion, or faceted shapes, can be qualitatively explained by the protein concentration dependencies and a force balance, taking into account the membrane tension, the density of anchoring points between the membrane and the actin network, and the forces exerted by molecular motors in the actin network. The identification of the physical mechanisms for shape transformations of active cytoskeletal vesicles sets a conceptual and quantitative benchmark for the further exploration of the adaptation mechanisms of cells.
- Published
- 2016
- Full Text
- View/download PDF
45. Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation.
- Author
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Bielmeier C, Alt S, Weichselberger V, La Fortezza M, Harz H, Jülicher F, Salbreux G, and Classen AK
- Subjects
- Animals, Epithelium metabolism, Larva growth & development, Cell Differentiation, Drosophila growth & development, Drosophila Proteins metabolism, Imaginal Discs growth & development, Morphogenesis
- Abstract
Although cellular tumor-suppression mechanisms are widely studied, little is known about mechanisms that act at the level of tissues to suppress the occurrence of aberrant cells in epithelia. We find that ectopic expression of transcription factors that specify cell fates causes abnormal epithelial cysts in Drosophila imaginal discs. Cysts do not form cell autonomously but result from the juxtaposition of two cell populations with divergent fates. Juxtaposition of wild-type and aberrantly specified cells induces enrichment of actomyosin at their entire shared interface, both at adherens junctions as well as along basolateral interfaces. Experimental validation of 3D vertex model simulations demonstrates that enhanced interface contractility is sufficient to explain many morphogenetic behaviors, which depend on cell cluster size. These range from cyst formation by intermediate-sized clusters to segregation of large cell populations by formation of smooth boundaries or apical constriction in small groups of cells. In addition, we find that single cells experiencing lateral interface contractility are eliminated from tissues by apoptosis. Cysts, which disrupt epithelial continuity, form when elimination of single, aberrantly specified cells fails and cells proliferate to intermediate cell cluster sizes. Thus, increased interface contractility functions as error correction mechanism eliminating single aberrant cells from tissues, but failure leads to the formation of large, potentially disease-promoting cysts. Our results provide a novel perspective on morphogenetic mechanisms, which arise from cell-fate heterogeneities within tissues and maintain or disrupt epithelial homeostasis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
46. Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing.
- Author
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Etournay R, Popović M, Merkel M, Nandi A, Blasse C, Aigouy B, Brandl H, Myers G, Salbreux G, Jülicher F, and Eaton S
- Subjects
- Animals, Biophysical Phenomena, Drosophila growth & development, Models, Biological, Pupa growth & development, Drosophila embryology, Epithelial Cells physiology, Epithelium physiology, Wings, Animal embryology
- Abstract
How tissue shape emerges from the collective mechanical properties and behavior of individual cells is not understood. We combine experiment and theory to study this problem in the developing wing epithelium of Drosophila. At pupal stages, the wing-hinge contraction contributes to anisotropic tissue flows that reshape the wing blade. Here, we quantitatively account for this wing-blade shape change on the basis of cell divisions, cell rearrangements and cell shape changes. We show that cells both generate and respond to epithelial stresses during this process, and that the nature of this interplay specifies the pattern of junctional network remodeling that changes wing shape. We show that patterned constraints exerted on the tissue by the extracellular matrix are key to force the tissue into the right shape. We present a continuum mechanical model that quantitatively describes the relationship between epithelial stresses and cell dynamics, and how their interplay reshapes the wing.
- Published
- 2015
- Full Text
- View/download PDF
47. Decrease in Cell Volume Generates Contractile Forces Driving Dorsal Closure.
- Author
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Saias L, Swoger J, D'Angelo A, Hayes P, Colombelli J, Sharpe J, Salbreux G, and Solon J
- Subjects
- Animals, Biomechanical Phenomena, Caspases metabolism, Drosophila metabolism, Drosophila Proteins metabolism, Embryo, Nonmammalian metabolism, Embryo, Nonmammalian ultrastructure, Epithelial Cells metabolism, Myosins metabolism, Phosphorylation, Serous Membrane cytology, Serous Membrane metabolism, Serous Membrane ultrastructure, Actin Cytoskeleton physiology, Cell Size, Drosophila embryology, Embryo, Nonmammalian cytology, Epithelial Cells cytology, Mechanotransduction, Cellular, Morphogenesis physiology
- Abstract
Biological tissues must generate forces to shape organs and achieve proper development. Such forces often result from the contraction of an apical acto-myosin meshwork. Here we describe an alternative mechanism for tissue contraction, based on individual cell volume change. We show that during Drosophila dorsal closure (DC), a wound healing-related process, the contraction of the amnioserosa (AS) is associated with a major reduction of the volume of its cells, triggered by caspase activation at the onset of the apoptotic program of AS cells. Cell volume decrease results in a contractile force that promotes tissue shrinkage. Estimating mechanical tensions with laser dissection and using 3D biophysical modeling, we show that the cell volume decrease acts together with the contraction of the actin cable surrounding the tissue to govern DC kinetics. Our study identifies a mechanism by which tissues generate forces and movements by modulating individual cell volume during development., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
48. Force transmission during adhesion-independent migration.
- Author
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Bergert M, Erzberger A, Desai RA, Aspalter IM, Oates AC, Charras G, Salbreux G, and Paluch EK
- Subjects
- Actins metabolism, Animals, Carcinoma 256, Walker, Cell Adhesion, Cell Line, Tumor, Integrins metabolism, Rats, Cell Movement physiology, Friction physiology, Stress, Mechanical
- Abstract
When cells move using integrin-based focal adhesions, they pull in the direction of motion with large, ∼100 Pa, stresses that contract the substrate. Integrin-mediated adhesions, however, are not required for in vivo confined migration. During focal adhesion-free migration, the transmission of propelling forces, and their magnitude and orientation, are not understood. Here, we combine theory and experiments to investigate the forces involved in adhesion-free migration. Using a non-adherent blebbing cell line as a model, we show that actin cortex flows drive cell movement through nonspecific substrate friction. Strikingly, the forces propelling the cell forward are several orders of magnitude lower than during focal-adhesion-based motility. Moreover, the force distribution in adhesion-free migration is inverted: it acts to expand, rather than contract, the substrate in the direction of motion. This fundamentally different mode of force transmission may have implications for cell-cell and cell-substrate interactions during migration in vivo.
- Published
- 2015
- Full Text
- View/download PDF
49. Spontaneous oscillations of elastic contractile materials with turnover.
- Author
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Dierkes K, Sumi A, Solon J, and Salbreux G
- Subjects
- Actomyosin chemistry, Actomyosin metabolism, Animals, Cell Shape physiology, Drosophila, Elasticity, Myosins chemistry, Myosins metabolism, Biological Clocks, Models, Biological
- Abstract
Single and collective cellular oscillations driven by the actomyosin cytoskeleton have been observed in numerous biological systems. Here, we propose that these oscillations can be accounted for by a generic oscillator model of a material turning over and contracting against an elastic element. As an example, we show that during dorsal closure of the Drosophila embryo, experimentally observed changes in actomyosin concentration and oscillatory cell shape changes can, indeed, be captured by the dynamic equations studied here. We also investigate the collective dynamics of an ensemble of such contractile elements and show that the relative contribution of viscous and friction losses yields different regimes of collective oscillations. Taking into account the diffusion of force-producing molecules between contractile elements, our theoretical framework predicts the appearance of traveling waves, resembling the propagation of actomyosin waves observed during morphogenesis.
- Published
- 2014
- Full Text
- View/download PDF
50. Stresses at the cell surface during animal cell morphogenesis.
- Author
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Clark AG, Wartlick O, Salbreux G, and Paluch EK
- Subjects
- Actin Cytoskeleton metabolism, Biomechanical Phenomena, Cell Enlargement, Cell Shape, Humans, Membrane Proteins metabolism, Muscle Contraction, Myosins metabolism, Actomyosin metabolism, Cell Membrane, Morphogenesis
- Abstract
Cell shape is determined by cellular mechanics. Cell deformations in animal cells, such as those required for cell migration, division or epithelial morphogenesis, are largely controlled by changes in mechanical stress and tension at the cell surface. The plasma membrane and the actomyosin cortex control surface mechanics and determine cell surface tension. Tension in the actomyosin cortex primarily arises from myosin-generated stresses and depends strongly on the ultrastructural architecture of the network. Plasma membrane tension is controlled mainly by the surface area of the membrane relative to cell volume and can be modulated by changing membrane composition, shape and the organization of membrane-associated proteins. We review here our current understanding of the control of cortex and membrane tension by molecular processes. We particularly highlight the need for studies that bridge the scales between microscopic events and emergent properties at the cellular level. Finally, we discuss how the mechanical interplay between membrane dynamics and cortex contractility is key to understanding the biomechanical control of cell morphogenesis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
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