Biologie cellulaire systémique de la polarité et de la division

Gallerie des publications

Note: this page is a work in progress! Not all of our publications are present here.



The nucleus acts as a ruler tailoring cell responses to spatial constraints (Science)

lomakin-scienceA. J. Lomakin, C. J. Cattin, D. Cuvelier, Z. Alraies, M. Molina, G. P. F. Nader, N. Srivastava,P. J. Saez, J. M. Garcia-Arcos, I. Y. Zhitnyak, A. Bhargava, M. K. Driscoll, E. S. Welf, R. Fiolka, R. J. Petrie,N. S. De Silva, J. M. González-Granado, N. Manel, A. M. Lennon-Duménil, D. J. Müller, M. Piel.

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.

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Myosin II Activity Is Selectively Needed for Migration in Highly Confined Microenvironments in Mature Dendritic Cells (Frontiers in Immunology)

mDCs migrating in microchannels
mDCs migrating in microchannels

Lucie Barbier, Pablo J Sáez, Rafaele Attia, Ana-Maria Lennon-Duménil, Ido Lavi, Matthieu Piel, Pablo Vargas We identified a specific role of MyoII activity in the regulation of mDCs migration in highly confined microenvironments. Using microfluidic systems, we observed that during mDCs chemotaxis in 3D collagen gels under defined CCL21 gradients, MyoII activity was required to sustain their fast speed but not to orientate them toward the chemokine.

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Macropinocytosis Overcomes Directional Bias in Dendritic Cells Due to Hydraulic Resistance and Facilitates Space Exploration (Developmental cell)

Barotactism with dendritic cells
Barotactism with dendritic cells

Hélène D Moreau, Carles Blanch-Mercader, Rafaele Attia, Mathieu Maurin, Zahraa Alraies, Doriane Sanséau, Odile Malbec, Maria-Graciela Delgado, Philippe Bousso, Jean-François Joanny, Raphaël Voituriez, Matthieu Piel, Ana-Maria Lennon-Duménil

The migration of immune cells can be guided by physical cues imposed by the environment, such as geometry, rigidity, or hydraulic resistance (HR). Neutrophils preferentially follow paths of least HR in vitro, a phenomenon known as barotaxis. The mechanisms and physiological relevance of barotaxis remain unclear. We show that barotaxis results from the amplification of a small force imbalance by the actomyosin cytoskeleton, resulting in biased directional choices.

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Reconstitution of cell migration at a glance (Journal Of Cell Science)

Reconstitution of cell migration

Juan Manuel Garcia-Arcos, Renaud Chabrier, Mathieu Deygas, Guilherme Nader, Lucie Barbier, Pablo José Sáez, Aastha Mathur, Pablo Vargas, Matthieu Piel

In this Cell Science at a Glance article and accompanying poster, we present selected experimental setups that mimic different events that cells undergo during migration in vivo. These include polydimethylsiloxane (PDMS) devices to deform whole cells or organelles, micro patterning, nano-fabricated structures like grooves, and compartmentalized collagen chambers with chemical gradients. We also outline the main contribution of each technique to the understanding of different aspects of single-cell migration.

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Polarization of Myosin II Refines Tissue Material Properties to Buffer Mechanical Stress. (Developmental Cell)

Circa 10-Cell Long Ablation in Anchored Tissue Expressing E-cad:GFP

Maria Duda, Natalie J Kirkland, Nargess Khalilgharibi, Melda Tozluoglu, Alice C Yuen, Nicolas Carpi, Anna Bove, Matthieu Piel, Guillaume Charras, Buzz Baum, Yanlan Mao Through the development of a tissue-stretching device, we uncover a mechanosensitive pathway that regulates tissue responses to mechanical stress through the polarization of actomyosin across the tissue. We show that stretch induces the formation of linear multicellular actomyosin cables, which depend on Diaphanous for their nucleation.

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Spontaneous migration of cellular aggregates from giant keratocytes to running spheroids (PNAS)

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

Grégory Beaune, Carles Blanch-Mercader, Stéphane Douezan, Julien Dumond, David Gonzalez-Rodriguez, Damien Cuvelier, Thierry Ondarçuhu, Pierre Sens, Sylvie Dufour, Michael P Murrell, Françoise Brochard-Wyart This manuscript details modes of collective migration and the role of tissue dewetting in generating a symmetry breaking, which drives the spontaneous migration of cell aggregates en masse. This discovery, its corresponding assay, and the establishment of the underlying fundamental physical principles provide a powerful platform for further in-depth studies and insights into biological migration at the mesoscopic scale.

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Size control in mammalian cells involves modulation of both growth rate and cell cycle duration. (Nature Communications)

fluorescence exclusion method
Fluorescence exclusion method (FxM)

Clotilde Cadart, Sylvain Monnier, Jacopo Grilli, Pablo J Sáez, Nishit Srivastava, Rafaele Attia, Emmanuel Terriac, Buzz Baum, Marco Cosentino-Lagomarsino, Matthieu Piel Direct measurements of single-cell volumes over entire cell cycles on various mammalian cell lines and primary human cells.

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Leukocyte Migration and Deformation in Collagen Gels and Microfabricated Constrictions (Methods in Molecular Biology)

saez tracks Pablo J Sáez, Lucie Barbier, Rafaele Attia, Hawa-Racine Thiam, Matthieu Piel, Pablo Vargas A multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21. Microfabricated channels connected to small constrictions

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ATP promotes the fast migration of dendritic cells through the activity of pannexin 1 channels and P2X7 receptors (Science Signaling)

vargas science signaling 2017
vargas science signaling 2017

Pablo J. Sáez, Pablo Vargas, Kenji F. Shoji, Paloma A. Harcha, Ana-María Lennon-Duménil, Juan C. Sáez. When dendritic cells (DCs) in peripheral tissues encounter danger-associated signals, such as microbial products or ATP released from damaged cells, they migrate to lymph nodes to activate T cells and initiate the adaptive immune response. Sáez et al. found that ATP stimulated P2X7 receptors in DCs, which resulted in the opening of pannexin 1 (Panx1) channels and the release of ATP as part of an autocrine loop that increased DC migration speed. DCs from Panx1-deficient mice migrated more slowly than did DCs from wild-type mice. When injected into the footpads of mice, ATP-treated Panx1-deficient DCs exhibited defective migration to draining lymph nodes. Together, these data suggest that P2X7 receptors and Panx1 channels facilitate the speedy migration of DCs to lymph nodes in response to danger signals.

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ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. (Science)

HeLa cell migrating through a constriction
HeLa cell migrating through a constriction

M Raab, M Gentili, H de Belly, H R Thiam, P Vargas, A J Jimenez, F Lautenschlaeger, Raphaël Voituriez, A M Lennon-Duménil, N Manel, M Piel We found that the nuclear envelope opened at high frequency in migrating mammalian cells during interphase, which allowed nuclear proteins to leak out and cytoplasmic proteins to leak in. This transient opening was caused by nuclear deformation and was rapidly repaired in an ESCRT (endosomal sorting complexes required for transport)–dependent manner.

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Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments. (Nature Communications)

bmdc migrating in microchannel with constriction
Immature BMDC passing constriction

Hawa-Racine Thiam, Pablo Vargas, Nicolas Carpi, Carolina Lage Crespo, Matthew Raab, Emmanuel Terriac, Megan C King, Jordan Jacobelli, Arthur S Alberts, Theresia Stradal, Ana-Maria Lennon-Dumenil, Matthieu Piel We show that dendritic cells possess a mechanism to pass through micrometric constrictions. This mechanism is based on a rapid Arp2/3-dependent actin nucleation around the nucleus that disrupts the nuclear lamina, the main structure limiting nuclear deformability.

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Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells. (Nature Cell Biology)

bmdc migration
Different modes of migration in BMDC

Pablo Vargas, Paolo Maiuri, Marine Bretou, Pablo J Sáez, Paolo Pierobon, Mathieu Maurin, Mélanie Chabaud, Danielle Lankar, Dorian Obino, Emmanuel Terriac, Matthew Raab, Hawa-Racine Thiam, Thomas Brocker, Susan M Kitchen-Goosen, Arthur S Alberts, Praveen Sunareni, Sheng Xia, Rong Li, Raphael Voituriez, Matthieu Piel, Ana-Maria Lennon-Duménil We show that the migration of immature DCs depends on two main actin pools: a RhoA–mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42–Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture.

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Arc/Arg3.1 governs inflammatory dendritic cell
migration from the skin and thereby controls
T cell activation (Science Immunology)

Vargas Science Immunology 2016Friederike Ufer, Pablo Vargas, Jan Broder Engler, Joseph Tintelnot, Benjamin Schattling, Hana Winkler, Simone Bauer, Nina Kursawe, Anne Willing, Oliver Keminer, Ora Ohana,
Gabriela Salinas-Riester, Ole Pless, Dietmar Kuhl, Manuel A. Friese.

Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activity regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) was strictly confined to migDCs. Mechanistically, Arc/Arg3.1 was required for accelerated DC migration during inflammation because it regulated actin dynamics through nonmuscle myosin II. Accordingly, Arc/Arg3.1 dependent DC migration was critical for mounting T cell responses in experimental autoimmune encephalomyelitis and allergic contact dermatitis. Thus, Arc/Arg3.1 was restricted to migDCs in the skin and drove fast DC migration by exclusively coordinating cytoskeletal changes in response to inflammatory challenges. These findings commend Arc/Arg3.1 as a universal switch in migDCs that may be exploited to selectively modify immune responses.

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Actin flows mediate a universal coupling between cell speed and cell persistence. (Cell)

Fluorescence Time-Lapse Movie of mBMDCs in 2D Confinement at 37°C
Fluorescence Time-Lapse Movie of mBMDCs in 2D Confinement

Paolo Maiuri, Jean-François Rupprecht, Stefan Wieser, Verena Ruprecht, Olivier Bénichou, Nicolas Carpi, Mathieu Coppey, Simon De Beco, Nir Gov, Carl-Philipp Heisenberg, Carolina Lage Crespo, Franziska Lautenschlaeger, Maël Le Berre, Ana-Maria Lennon-Dumenil, Matthew Raab, Hawa-Racine Thiam, Matthieu Piel, Michael Sixt, Raphaël Voituriez We show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale.

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Confinement and Low Adhesion Induce Fast Amoeboid Migration of Slow Mesenchymal Cells (Cell).

TIRF microscopy of Myosin II in HeLa Kyoto under confinement
TIRF microscopy of Myosin II in HeLa Kyoto under confinement

Yan-Jun Liu, Maël Le Berre, Franziska Lautenschlaeger, Paolo Maiuri, Andrew Callan-Jones, Mélina Heuzé, Tohru Takaki, Raphaël Voituriez, Matthieu Piel We investigated how confinement and adhesion affect mesenchymal-amoeboid transition. We report that, in the absence of focal adhesions and under conditions of confinement, mesenchymal cells can spontaneously switch to a fast amoeboid migration phenotype.

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ESCRT machinery is required for plasma membrane repair. (Science)

jimenez science 2014Jimenez AJ, Maiuri P, Lafaurie-Janvore J, Divoux S, Piel M, Perez F. Plasma membrane damage can be triggered by numerous phenomena, and efficient repair is essential for cell survival. Endocytosis, membrane patching, or extracellular budding can be used for plasma membrane repair. We found that endosomal sorting complex required for transport (ESCRT), involved previously in membrane budding and fission, plays a critical role in plasma membrane repair. ESCRT proteins were recruited within seconds to plasma membrane wounds. Quantitative analysis of wound closure kinetics coupled to mathematical modeling suggested that ESCRTs are involved in the repair of small wounds. Real-time imaging and correlative scanning electron microscopy (SEM) identified extracellular buds and shedding at the site of ESCRT recruitment. Thus, the repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions.

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ESCRT-III Assembly and Cytokinetic Abscission Are Induced by Tension Release in the Intercellular Bridge (Science)

abcission bridge
ESCRT-III cutting the bridge

Julie Lafaurie-Janvore, Paolo Maiuri, Irène Wang, Mathieu Pinot, Jean-Baptiste Manneville, Timo Betz, Martial Balland, Matthieu Piel We found that pulling forces exerted by daughter cells on the intercellular bridge appear to regulate abscission. Counterintuitively, these forces prolonged connection, whereas a release of tension induced abscission.

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