Search

Your search keyword '"Damien Cuvelier"' showing total 16 results
Start Over Author "Damien Cuvelier" Publication Year Range Last 10 years
16 results on '"Damien Cuvelier"'

1. Applying mechanical forces on Drosophila tissues in vivo using the StretchCo, a 3D-printable device

Author

Mélanie Gracia, Bénédicte M. Lefèvre, Raquel Güell Alonso, Victoire Cachoux, Maria Balakireva, Boris Guirao, Damien Cuvelier, Allison J. Bardin, and Yohanns Bellaïche

Subjects
Biophysics, Developmental biology, Science (General), Q1-390
Abstract

Summary: Applying mechanical forces to tissues helps to understand morphogenesis and homeostasis. Additionally, recording the dynamics of living tissues under mechanical constraints is needed to explore tissue biomechanics. Here, we present a protocol to 3D-print a StretchCo device and use it to apply uniaxial mechanical stress on the Drosophila pupal dorsal thorax epithelium. We describe steps for 3D printing, polydimethylsiloxane (PDMS) strip cutting, and glue preparation. We detail procedures for PDMS strip mounting, tissue compaction, and live imaging upon force application. For additional details on the use and execution of this protocol, please refer to Cachoux et al. (2023)1 from which the StretchCo machine has been derived. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Published
2024
Full Text
View/download PDF

2. A mechano-osmotic feedback couples cell volume to the rate of cell deformation

Author

Larisa Venkova, Amit Singh Vishen, Sergio Lembo, Nishit Srivastava, Baptiste Duchamp, Artur Ruppel, Alice Williart, Stéphane Vassilopoulos, Alexandre Deslys, Juan Manuel Garcia Arcos, Alba Diz-Muñoz, Martial Balland, Jean-François Joanny, Damien Cuvelier, Pierre Sens, and Matthieu Piel

Subjects
cell volume, membrane tension, cell shape, Medicine, Science, Biology (General), QH301-705.5
Abstract

Mechanics has been a central focus of physical biology in the past decade. In comparison, how cells manage their size is less understood. Here, we show that a parameter central to both the physics and the physiology of the cell, its volume, depends on a mechano-osmotic coupling. We found that cells change their volume depending on the rate at which they change shape, when they spontaneously spread or when they are externally deformed. Cells undergo slow deformation at constant volume, while fast deformation leads to volume loss. We propose a mechanosensitive pump and leak model to explain this phenomenon. Our model and experiments suggest that volume modulation depends on the state of the actin cortex and the coupling of ion fluxes to membrane tension. This mechano-osmotic coupling defines a membrane tension homeostasis module constantly at work in cells, causing volume fluctuations associated with fast cell shape changes, with potential consequences on cellular physiology.

Published
2022
Full Text
View/download PDF

3. Actin Stress Fibers Response and Adaptation under Stretch

Author

Roberto Bernal, Milenka Van Hemelryck, Basile Gurchenkov, and Damien Cuvelier

Subjects
actin stress fibers, cell mechanics, SF response, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

One of the many effects of soft tissues under mechanical solicitation in the cellular damage produced by highly localized strain. Here, we study the response of peripheral stress fibers (SFs) to external stretch in mammalian cells, plated onto deformable micropatterned substrates. A local fluorescence analysis reveals that an adaptation response is observed at the vicinity of the focal adhesion sites (FAs) due to its mechanosensor function. The response depends on the type of mechanical stress, from a Maxwell-type material in compression to a complex scenario in extension, where a mechanotransduction and a self-healing process takes place in order to prevent the induced severing of the SF. A model is proposed to take into account the effect of the applied stretch on the mechanics of the SF, from which relevant parameters of the healing process are obtained. In contrast, the repair of the actin bundle occurs at the weak point of the SF and depends on the amount of applied strain. As a result, the SFs display strain-softening features due to the incorporation of new actin material into the bundle. In contrast, the response under compression shows a reorganization with a constant actin material suggesting a gliding process of the SFs by the myosin II motors.

Published
2022
Full Text
View/download PDF

4. Phenotyping polarization dynamics of immune cells using a lipid droplet-cell pairing microfluidic platform

Author

Léa Pinon, Nicolas Ruyssen, Judith Pineau, Olivier Mesdjian, Damien Cuvelier, Anna Chipont, Rachele Allena, Coralie L. Guerin, Sophie Asnacios, Atef Asnacios, Paolo Pierobon, and Jacques Fattaccioli

Subjects
Genetics, Radiology, Nuclear Medicine and imaging, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Computer Science Applications, Biotechnology
Abstract

The immune synapse is the tight contact zone between a lymphocyte and a cell presenting its cognate antigen. This structure serves as a signaling platform and entails a polarization of intracellular components necessary to the immunological function of the cell. While the surface properties of the presenting cell are known to control the formation of the synapse, their impact on polarization has not yet been studied. Using functional lipid droplets as tunable artificial presenting cells combined with a microfluidic pairing device, we simultaneously observe synchronized synapses and dynamically quantify polarization patterns of individual B cells. By assessing how ligand concentration, surface fluidity, and substrate rigidity impact lysosome polarization, we show that its onset and kinetics depend on the local antigen concentration at the synapse and on substrate rigidity. Our experimental system enables a fine phenotyping of monoclonal cell populations based on their synaptic readout.

Published
2022

6. Compressive forces stabilise microtubules in living cells

Author

Yuhui Li, Ondřej Kučera, Damien Cuvelier, David M. Rutkowski, Mathieu Deygas, Dipti Rai, Tonja Pavlovič, Filipe Nunes Vicente, Matthieu Piel, Gregory Giannone, Dimitrios Vavylonis, Anna Akhmanova, Laurent Blanchoin, and Manuel Théry

Abstract

Cell mechano-sensation and adaptation are supported by the actin network. The microtubule network is not considered to be directly sensitive to mechanical forces acting on a cell. However, recent studies on isolated microtubulesin vitrohave shown that bending forces have an impact on their structure, composition and lifespan, suggesting that, in a cellular context, microtubules may react to mechanical forces. We tested this hypothesis in living cells by subjecting them to cycles of compressive forces and found that microtubules became distorted, less dynamic and more stable. This mechano-stabilisation depends on CLASP2, which relocates from the end to the deformed shaft of microtubules. These results demonstrate that microtubules in living cells have mechano-responsive properties that allow them to resist and even counteract the forces to which they are subjected.

Published
2022

7. Phenotyping Polarization Dynamics Of Immune Cells Using A Lipid Droplet - Cell Pairing Microfluidic Platform

Author

Léa Pinon, Nicolas Ruyssen, Judith Pineau, Olivier Mesdjian, Damien Cuvelier, Anna Chipont, Rachele Allena, Coralie L. Guerin, Sophie Asnacios, Atef Asnacios, Paolo Pierobon, Jacques Fattaccioli, Institut de Biomécanique Humaine Georges Charpak (IBHGC), Université Sorbonne Paris Nord-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Curie [Paris], Physico-Chimie-Curie (PCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biomécanique (LBM), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Sorbonne Université - Faculté de Physique (UFR 925), Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physicochimie des Electrolytes, Colloïdes et Sciences Analytiques (PECSA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Colloïdes et Matériaux Divisés (LCMD), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph]
Abstract

The immune synapse is the tight contact zone between a lymphocyte and a cell presenting its cognate antigen. This structure serves as a signaling platform and entails a polarization of intra-cellular components, necessary to the immunological function of the cell. While the surface properties of the presenting cell are known to control the formation of the synapse, their impact on polarization has not yet been studied.Using functional lipid droplets as tunable artificial presenting cells combined with a microfluidic pairing device, we simultaneously observe synchronized synapses and dynamically quantify polarization patterns of individual B cells. By assessing how ligand concentration, surface fluidity and substrate rigidity impact lysosome polarization, we show that its onset and kinetics depend on the local antigen concentration at the synapse and on substrate rigidity. Our experimental system enables a fine phenotyping of monoclonal cell populations based on their synaptic readout.

Published
2021

8. A mechano-osmotic feedback couples cell volume to the rate of cell deformation

Author

Martial Balland, Stéphane Vassilopoulos, Nishit Srivastava, Jean-François Joanny, Artur Ruppel, Baptiste Duchamp, Matthieu Piel, Alba Diz-Muñoz, Amit Singh Vishen, Juan Manuel Garcia Arcos, Larisa Venkova, Alexandre Deslys, Sergio Lembo, Pierre Sens, Damien Cuvelier, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre-Gilles de Gennes pour la Microfluidique, Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory [Heidelberg] (EMBL), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de Recherche en Myologie, and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cell physiology, 0303 health sciences, Work (thermodynamics), Cell volume, Deformation (meteorology), Coupling (electronics), 03 medical and health sciences, 0302 clinical medicine, Volume (thermodynamics), [PHYS.COND.CM-GEN]Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other], Biophysics, 030217 neurology & neurosurgery, Actin, 030304 developmental biology, Cell deformation
Abstract

Mechanics has been a central focus of physical biology in the past decade. In comparison, the osmotic and electric properties of cells are less understood. Here we show that a parameter central to both the physics and the physiology of the cell, its volume, depends on a mechano-osmotic coupling. We found that cells change their volume depending on the rate at which they change shape, when they spread, migrate or are externally deformed. Cells undergo slow deformation at constant volume, while fast deformation leads to volume loss. We propose a mechano-sensitive pump and leak model to explain this phenomenon. Our model and experiments suggest that volume modulation depends on the state of the actin cortex and the coupling of ion fluxes to membrane tension. This mechano-osmotic coupling defines a membrane tension homeostasis module constantly at work in cells, causing volume fluctuations associated with fast cell shape changes, with potential consequences on cellular physiology.

Published
2021

9. Hematopoietic progenitors polarize in contact with bone marrow stromal cells in response to SDF1

Author

Khansa Saadallah, Benoit Vianay, Stephane Brunet, Jérôme Larghero, Adrian Candelas, Alexandre Schaeffer, Laurent Blanchoin, Samy Gobaa, Thierry Jaffredo, Damien Cuvelier, Julien Lion, Nuala Mooney, Thomas Bessy, Lionel Faivre, Jean-Christophe Bories, Manuel Thery, Cecilia Nakid-Cordero, Benoit Souquet, CytoMorphoLab, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Institut Pierre-Gilles de Gennes pour la Microfluidique, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Plateforme technologique Biomatériaux et Microfluidique - Biomaterials and Microfluidics technologic Platform, Institut Pasteur [Paris], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratoire de Biologie du Développement [Paris] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was funded by grants from the Agence Nationale de la Recherche (ANR-14-CE11-0012, ANR-10-IHUB-0002), the European Research Council (ERC CoG 771599), the Emergence program of the Ville de Paris, the 'Coups d’Elan' prize of the Fondation Bettencourt Schueller, and the Fondation Schlumberger pour l’Education et la Recherche. T. Bessy received a PhD fellowship from the Université de Paris and the Ligue Contre le Cancer. The facility is supported by the Conseil Régional, Île-de-France, Canceropôle Ile-de-France, Université de Paris, Association Saint-Louis, Association Jean-Bernard, Fondation pour la Recherche Médicale, the French Institut National Du Cancer, and Ministère de la Recherche., ANR-14-CE11-0012,STAR,Architectures des cellules souches : Rôle des interactions cellules souches hematopoïétiques et mésenchymateuses dans le contrôle de leur polarisation et de l'asymétrie de leurs divisions cellulaires.(2014), ANR-10-IBHU-0002,SLI,Institut Saint-Louis(2010), European Project: 771599,ICEBERG, Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire de Biologie du Développement [IBPS] (LBD), Mooney, Nuala, Appel à projets générique - Architectures des cellules souches : Rôle des interactions cellules souches hematopoïétiques et mésenchymateuses dans le contrôle de leur polarisation et de l'asymétrie de leurs divisions cellulaires. - - STAR2014 - ANR-14-CE11-0012 - Appel à projets générique - VALID, Instituts Hospitalo-Universitaires B - Institut Saint-Louis - - SLI2010 - ANR-10-IBHU-0002 - IBHU - VALID, and Exploration below the tip of the microtubule - ICEBERG - 771599 - INCOMING

Subjects
Stromal cell, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Biology, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, Microtubule, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Humans, Progenitor cell, Cytoskeleton, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Endothelial Cells, Mesenchymal Stem Cells, Cell Biology, Hematopoietic Stem Cells, Chemokine CXCL12, Cell biology, Haematopoiesis, medicine.anatomical_structure, Centrosome, 030220 oncology & carcinogenesis, Bone marrow, Stem cell
Abstract

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).; International audience; The fate of hematopoietic stem and progenitor cells (HSPCs) is regulated by their interaction with stromal cells in the bone marrow. However, the cellular mechanisms regulating HSPC interaction with these cells and their potential impact on HSPC polarity are still poorly understood. Here we evaluated the impact of cell–cell contacts with osteoblasts or endothelial cells on the polarity of HSPC. We found that an HSPC can form a discrete contact site that leads to the extensive polarization of its cytoskeleton architecture. Notably, the centrosome was located in proximity to the contact site. The capacity of HSPCs to polarize in contact with stromal cells of the bone marrow appeared to be specific, as it was not observed in primary lymphoid or myeloid cells or in HSPCs in contact with skin fibroblasts. The receptors ICAM, VCAM, and SDF1 were identified in the polarizing contact. Only SDF1 was independently capable of inducing the polarization of the centrosome–microtubule network.

Published
2021

10. Nuclear fragility, blaming the blebs

Author

Romain Rollin, Guilherme Pedreira de Freitas Nader, Matthieu Piel, Alexis J. Lomakin, Alice Williart, Damien Cuvelier, and Nishit Srivastava

Subjects
Cell Nucleus, 0303 health sciences, 2019-20 coronavirus outbreak, genetic structures, Coronavirus disease 2019 (COVID-19), Nuclear Envelope, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Cell Membrane, Cell Biology, Biology, 03 medical and health sciences, Cell nucleus, 0302 clinical medicine, Fragility, medicine.anatomical_structure, medicine, Biophysics, Humans, Nucleus, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Although textbook pictures depict the cell nucleus as a simple ovoid object, it is now clear that it adopts a large variety of shapes in tissues. When cells deform, because of cell crowding or migration through dense matrices, the nucleus is subjected to large constraints that alter its shape. In this review, we discuss recent studies related to nuclear fragility, focusing on the surprising finding that the nuclear envelope can form blebs. Contrary to the better-known plasma membrane blebs, nuclear blebs are unstable and almost systematically lead to nuclear envelope opening and uncontrolled nucleocytoplasmic mixing. They expand, burst, and repair repeatedly when the nucleus is strongly deformed. Although blebs are a major source of nuclear instability, they are poorly understood so far, which calls for more in-depth studies of these structures.

Published
2020

11. The nucleus acts as a ruler tailoring cell responses to spatial constraints

Author

Cedric J. Cattin, Juan Manuel Garcia-Arcos, Z. Alraies, M. Molina, Ana-Maria Lennon-Duménil, Ryan J. Petrie, Reto Fiolka, N. S. De Silva, Meghan Driscoll, Matthieu Piel, Alexis J. Lomakin, Guilherme Pedreira de Freitas Nader, Pablo J. Sáez, Anvita Bhargava, Erik S. Welf, Nishit Srivastava, Daniel J. Müller, Damien Cuvelier, Irina Y. Zhitnyak, J. M. González-Granado, Nicolas Manel, and Institut Curie [Paris]

Subjects
Cell Nucleus, 0303 health sciences, Cytoplasm, Multidisciplinary, Chemistry, [SDV]Life Sciences [q-bio], Cell, Proprioception, Article, Cortex (botany), Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Cell Movement, Cell Line, Tumor, Organelle, Cancer cell, medicine, Mechanotransduction, Signal transduction, Process (anatomy), Nucleus, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler–based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.

Published
2020

12. Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs

Author

Edgar R. Gomes, Pietro Salvatore Carollo, Cécile Sykes, Bruno Cadot, Théophile Déjardin, François Sipieter, Cynthia Seiler, Damien Cuvelier, Patricia M. Davidson, Nicolas Borghi, Institut Jacques Monod (IJM (UMR_7592)), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de recherche en Myologie – U974 SU-INSERM, Repositório da Universidade de Lisboa, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)

Subjects
Epithelial-Mesenchymal Transition, [SDV]Life Sciences [q-bio], LINC complex, Cell, Biophysics, Biology, Mechanotransduction, Cellular, Article, 03 medical and health sciences, 0302 clinical medicine, Cell Signaling, medicine, Epithelial–mesenchymal transition, Cytoskeleton, Integral membrane protein, beta Catenin, 030304 developmental biology, Cell Nucleus, 0303 health sciences, Nesprin, Migration, Motility, Nuclear Proteins, Cell Biology, Transmembrane protein, 3. Good health, Cell biology, medicine.anatomical_structure, Signal transduction, 030217 neurology & neurosurgery
Abstract

© 2020 Déjardin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/)., LINC complexes are transmembrane protein assemblies that physically connect the nucleoskeleton and cytoskeleton through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in a nesprin protein of the LINC complex of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic, and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that nesprin experiences tension generated by the cytoskeleton and acts as a mechanical sensor of cell packing. Moreover, nesprin discriminates between inductions of partial and complete epithelial-mesenchymal transitions. We identify the implicated mechanisms, which involve α-catenin capture at the nuclear envelope by nesprin upon its relaxation, thereby regulating β-catenin transcription. Our data thus implicate LINC complex proteins as mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the epithelial-mesenchymal transition program., This material is based on work supported by the Centre national de la recherche scientifique (CNRS), Agence nationale de la recherche (ANR; grants ANR-13-JSV5-0007 and ANR-14-CE09-0006), France BioImaging (ANR-10-INBS-04), la Ligue contre le Cancer (REMX17751 to P.M. Davidson), and the Fondation ARC pour la Recherche sur le Cancer (PDF20161205227 to P.M. Davidson). P.S. Carollo has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation (Marie Skłodowska-Curie grant agreement 665850-INSPIRE) and acknowledges the Ecole Doctorale Frontières de l'Innovation en Recherche et Éducation (FIRE) Programme Bettencourt. E.R. Gomes was supported by a European Research Council consolidator grant (617676).

Published
2020

13. The nucleus acts as a ruler tailoring cell responses to spatial constraints

Author

Irina Y. Zhitnyak, Z. Alraies, M. Molina, Daniel J. Müller, Alexis J. Lomakin, Ryan J. Petrie, Guilherme Pedreira de Freitas Nader, Reto Fiolka, Erik S. Welf, Nishit Srivastava, Ana-Maria Lennon-Duménil, Matthieu Piel, Cedric J. Cattin, Meghan Driscoll, Juan Manuel Garcia-Arcos, Anvita Bhargava, Nicolas Manel, and Damien Cuvelier

Subjects
0303 health sciences, business.product_category, Chemistry, Cell, Cortex (botany), Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Ruler, Organelle, Cancer cell, medicine, Signal transduction, business, Process (anatomy), Nucleus, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. Here, we found that cells measure the degree of spatial confinement using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortexvianuclear envelope stretch-sensitive proteins, upregulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force enabling their passage through restrictive pores in complex three-dimensional (3D) environments, a process relevant to cancer cell invasion, immune responses and embryonic development.One Sentence SummaryNuclear envelope expansion above a threshold triggers a contractile cell response and thus acts as a ruler for the degree of cell deformation.

Published
2019
Full Text
View/download PDF

14. LINC complexes are mechanotransducers that discriminate Epithelial-Mesenchymal Transition programs

Author

Cynthia Seiler, Bruno Cadot, Cécile Sykes, Patricia M. Davidson, Nicolas Borghi, Damien Cuvelier, Théophile Déjardin, Pietro Salvatore Carollo, Edgar R. Gomes, Institut de Science des Matériaux de Mulhouse (IS2M), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), Physico-Chimie-Curie (PCC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Instituto de Medicina Molecular (iMM), Faculdade de Medicina [Lisboa], Universidade de Lisboa (ULISBOA)-Universidade de Lisboa (ULISBOA), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Nesprin, Chemistry, LINC complex, [SDV]Life Sciences [q-bio], Cell, Transmembrane protein, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Förster resonance energy transfer, medicine.anatomical_structure, Transcription (biology), medicine, Epithelial–mesenchymal transition, Cytoskeleton, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

LINC complexes are transmembrane protein assemblies that physically connect the nucleo- and cytoskeletons through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular disorders. The mechanical roles of LINC complexes in these contexts are poorly understood. To address this, we used genetically encoded FRET biosensors of molecular tension in LINC complex proteins of fibroblastic and epithelial cells in culture. We exposed cells to mechanical, genetic and pharmacological perturbations, mimicking a range of physiological and pathological situations. We show that LINC complex proteins experience tension generated by the cytoskeleton and act as mechanical sensors of cell packing. Moreover, the LINC complex discriminates between inductions of partial and complete epithelial-mesenchymal transitions (EMT). We identify the implicated mechanisms, which associate nesprin tension sensing with α-catenin capture at the nuclear envelope, thereby regulating β-catenin transcription. Our data thus implicate that LINC complexes are mechanotransducers that fine-tune β-catenin signaling in a manner dependent on the Epithelial-Mesenchymal Transition program.

Published
2019

15. Spontaneous migration of cellular aggregates from giant keratocytes to running spheroids

Author

Pierre Sens, David Gonzalez-Rodriguez, Thierry Ondarçuhu, Michael P. Murrell, Stéphane Douezan, Grégory Beaune, Carles Blanch-Mercader, Sylvie Dufour, Julien Dumond, Françoise Brochard-Wyart, Damien Cuvelier, Physico-Chimie-Curie (PCC), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'hydrodynamique (LadHyX), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'élaboration de matériaux et d'études structurales (CEMES), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Biologie des organismes marins et écosystèmes (BOME), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN), The James Franck Institute, Institute Biophysical Dynamics, University of Chicago, Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Sorbonne Université (FRANCE), Université Paris Est Créteil Val de Marne - UPEC (FRANCE), Université Pierre et Marie Curie, Paris 6 - UPMC (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université de Genève (SWITZERLAND), PSL Research University (FRANCE), Université de Lorraine (FRANCE), Yale University (USA), Laboratoire de Chimie et Physique-Approche Multi-échelle des Milieux Complexes - LCP-A2MC (Metz, France), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Université de Genève (UNIGE), Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC), Université de Lorraine (UL), Biologie Cellulaire et Cancer, Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Yale University [New Haven], Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Eq. 6 - Morphogenèse et génétique moléculaire (Inserm U955 - IMRB), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Genève = University of Geneva (UNIGE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut National Polytechnique de Toulouse - INPT (FRANCE)

Subjects
0301 basic medicine, Materials science, Mécanique des fluides, Dewetting, Cell Culture Techniques, Nucleation, Rigidity (psychology), Cell Communication, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Reactive wetting, Mice, 03 medical and health sciences, Cell Movement, Spheroids, Cellular, Monolayer, Animals, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Cell Aggregation, Multidisciplinary, Dynamics (mechanics), Spheroid, Adhesion, Cell aggregate, Bipedal stick–slip motion, 030104 developmental biology, Collective migration, [PHYS.COND.CM-GEN]Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other], Physical Sciences, Biophysics, Biologie cellulaire, Lamellipodium
Abstract

International audience; Despite extensive knowledge on the mechanisms that drive singlecell migration, those governing the migration of cell clusters, as occurring during embryonic development and cancer metastasis,remain poorly understood. Here, we investigate the collective migration of cell on adhesive gels with variable rigidity, using 3D cellular aggregates as a model system. After initial adhesion to the substrate, aggregates spread by expanding outward a cell monolayer, whose dynamics is optimal in a narrowrange of rigidities. Fast expansion gives rise to the accumulation of mechanical tension that leads to the rupture of cell–cell contacts and the nucleation of holes within the monolayer, which becomes unstable and undergoes dewetting like a liquid film. This leads to a symmetry breaking and causes the entire aggregate to move as a single entity. Varying the substrate rigidity modulates the extent of dewetting and induces different modes of aggregate motion: “giant keratocytes,” where the lamellipodium is a cell monolayer that expands at the front and retracts at the back; “penguins,” characterized by bipedal locomotion; and “running spheroids,” for nonspreading aggregates. We characterize these diversemodes of collectivemigration by quantifying the flows and forces that drive them, andwe unveil the fundamental physical principles that govern these behaviors, which underscore the biological predisposition of living material to migrate, independent of length scale.

Published
2018

16. Mechanotransduction at the Nuclear Envelope

Author

Théophile Déjardin, Damien Cuvelier, Edgar R. Gomes, Cynthia Seiler, Philippe Girard, Cécile Sykes, Patricia M. Davidson, Cadot Bruno, and Nicolas Borghi

Subjects
Förster resonance energy transfer, Binding protein, LINC complex, Biophysics, Adhesion, Mechanotransduction, Biology, Cytoskeleton, Transmembrane protein, Actin, Cell biology
Abstract

LINC complexes are transmembrane protein assemblies that physically connect the nucleo- and cytoskeletons through the nuclear envelope. Dysfunctions of LINC complexes are associated with pathologies such as cancer and muscular dystrophies. The mechanical roles of LINC complex proteins in these contexts are poorly understood. To address this issue, we have developed genetically encoded FRET biosensors that measure molecular tension in LINC complex proteins.We have evidenced that LINC complex proteins are under tension generated by the cytoskeleton and sensitive to various external and internal mechanical constraints in fibroblastic and epithelial cells. In addition, we have shown that some of the same constraints result in the localization at the nuclear envelope of alpha-catenin, an actin- binding protein required for intercellular adhesion that can also act as a transcription regulator. These results are consistent with a mechanotransduction activity of LINC complex proteins, the targets of which we currently investigate.

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results