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Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics
Antoine Blin, Anne Le Goff, Aurélie Magniez, Sonia Poirault-Chassac, Bruno Teste, Géraldine Sicot, Kim Anh Nguyen, Feriel S. Hamdi, Mathilde Reyssat & Dominique Baruch
Nature - Scientific Reports 6 21700 - DOI: 10.1038/srep21700 - 2019
We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF-coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour). Since platelets are produced in such a large amount, their extensive biological characterisation is possible and shows that platelets produced in this bioreactor are functional.
Droplet generation at Hele-Shaw microfluidic T-junction
I. Chakraborty, J. Ricouvier, P. Yazghur, P. Tabeling, A. Leshansky
Phys. Fluids - 31(2) 022010 - - 2019
Foam as a self-assembling amorphous photonic band gap material
View ORCID ProfileJoshua Ricouvier, Patrick Tabeling, and Pavel Yazhgur
Phys. Fluids - 116 (19) 9202-9207 - doi.org/10.1073/pnas.1820526116 - 2019
We show that slightly polydisperse disordered 2D foams can be used as a self-assembled template for isotropic photonic band gap (PBG) materials for transverse electric (TE) polarization. Calculations based on in-house experimental and simulated foam structures demonstrate that, at sufficient refractive index contrast, a dry foam organization with threefold nodes and long slender Plateau borders is especially advantageous to open a large PBG. A transition from dry to wet foam structure rapidly closes the PBG mainly by formation of bigger fourfold nodes, filling the PBG with defect modes. By tuning the foam area fraction, we find an optimal quantity of dielectric material, which maximizes the PBG in experimental systems. The obtained results have a potential to be extended to 3D foams to produce a next generation of self-assembled disordered PBG materials, enabling fabrication of cheap and scalable photonic devices.
Droplet generation at Hele-Shaw microfluidic T-junction
I. Chakraborty, J. Ricouvier, P. Yazhgur, P. Tabeling, and A. M. Leshansky,
Phys. Fluids - 31 2 - doi.org/10.1063/1.5086808 - 2019
We proposed the combined numerical and experimental study of the dynamics of droplets generation at shallow microfluidic T-junction, where the flow is strongly confined in the vertical direction. The numerical simulation is performed by employing quasi-2D Hele-Shaw approximation with an interface capturing procedure based on coupled Level-Set and Volume-of-Fluid methods. We investigate the effect of the capillary number, Ca, the channel geometry (cross section aspect ratio, χ), and the flow rate (disperse-to-continuous phases) ratio, Γ, on the dynamics of the droplet breakup. Depending on Ca, three distinct flow regimes are identified: squeezing, tearing and jetting. In the squeezing regime at low Ca, the size of the generated droplets depends on χ and Γ, while it is almost insensitive to Ca in agreement to previous studies. In the tearing regime at moderate Ca, the droplet size decreases as ∼Ca−1/3, while it is only a weak function of χ and Γ. Finally, in the jetting regime, the steady co-flow of both phases takes place at high enough Ca. The numerical predictions based on the Hele-Shaw flow approximation are in excellent agreement with our in-house experimental results, demonstrating that the proposed approach can be effectively used for computationally inexpensive and adequately accurate modeling of biphasic flows in shallow microfluidic devices.
Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells.
Vargas P, Maiuri P, Bretou M, Sáez PJ, Pierobon P, Maurin M, Chabaud M, Lankar D, Obino D, Terriac E, Raab M, Thiam H-R, Brocker T, Kitchen-Goosen SM, Alberts AS, Sunareni P, Xia S, Li R, Voituriez R, Piel M, Lennon-Duménil A-M
Nat. Cell Biol. - 18(1): 43-53 - DOI: 10.1016/j.jim.2015.12.005 - 2019
Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, 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. Following TLR4-MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function.
Optical volume and mass measurements show that mammalian cells swell during mitosis.
Zlotek-Zlotkiewicz E, Monnier S, Cappello G, Le Berre M, Piel M
J. Cell Biol. - 211( 4): 765-74 - DOI: 10.1016/j.jim.2015.12.005 - 2019
The extent, mechanism, and function of cell volume changes during specific cellular events, such as cell migration and cell division, have been poorly studied, mostly because of a lack of adequate techniques. Here we unambiguously report that a large range of mammalian cell types display a significant increase in volume during mitosis (up to 30%). We further show that this increase in volume is tightly linked to the mitotic state of the cell and not to its spread or rounded shape and is independent of the presence of an intact actomyosin cortex. Importantly, this volume increase is not accompanied by an increase in dry mass and thus corresponds to a decrease in cell density. This mitotic swelling might have important consequences for mitotic progression: it might contribute to produce strong pushing forces, allowing mitotic cells to round up; it might also, by lowering cytoplasmic density, contribute to the large change of physicochemical properties observed in mitotic cells.
Actin Flows Mediate a Universal Coupling between Cell Speed and Cell Persistence.
Maiuri P, Rupprecht J-F, Wieser S, Ruprecht V, Bénichou O, Carpi N, Coppey M, De Beco S, Gov N, Heisenberg C-P, Lage Crespo C, Lautenschlaeger F, Le Berre M, Lennon-Dumenil A-M, Raab M, Thiam H-R, Piel M, Sixt M, Voituriez R
Cell - 161(2) 374-86 - DOI: 10.1016/j.cell.2015.01.056 - 2019
Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, 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. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns.
Deterministic patterns in cell motility
Ido Lavi, Matthieu Piel, Ana-Maria Lennon-Duménil , Raphaël Voituriez and Nir S. Gov
Nature Physics - 12 1146–1152 - DOI: : 10.1038/NPHYS3836 - 2019
Cell migration paths are generally described as random walks, associated with both intrinsic and extrinsic noise. However, complex cell locomotion is not merely related to such fluctuations, but is often determined by the underlying machinery. Cell motility is driven mechanically by actin and myosin, two molecular components that generate contractile forces. Other cell functions make use of the same components and, therefore, will compete with the migratory apparatus. Here, we propose a physical model of such a competitive system, namely dendritic cells whose antigen capture function and migratory ability are coupled by myosin II. The model predicts that this coupling gives rise to a dynamic instability, whereby cells switch from persistent migration to unidirectional self-oscillation, through a Hopf bifurcation. Cells can then switch to periodic polarity reversals through a homoclinic bifurcation. These predicted dynamic regimes are characterized by robust features that we identify through in vitro trajectories of dendritic cells over long timescales and distances. We expect that competition for limited resources in other migrating cell types can lead to similar deterministic migration modes.
Polarization of Myosin II Refines Tissue Material Properties to Buffer Mechanical Stress.
Duda M, Kirkland NJ, Khalilgharibi N, Tozluoglu M, Yuen AC, Carpi N, Bove A, Piel M, Charras G, Baum B, Mao Y.
Dev Cell - 48(2) 245-260. - doi: 10.1016/j.devcel.2018.12.020. - 2019
As tissues develop, they are subjected to a variety of mechanical forces. Some of these forces are instrumental in the development of tissues, while others can result in tissue damage. Despite our extensive understanding of force-guided morphogenesis, we have only a limited understanding of how tissues prevent further morphogenesis once the shape is determined after development. Here, 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. These stiffen the epithelium, limiting further changes in shape, and prevent fractures from propagating across the tissue. Overall, this mechanism of force-induced changes in tissue mechanical properties provides a general model of force buffering that serves to preserve the shape of tissues under conditions of mechanical stress.
Myosin II Activity Is Selectively Needed for Migration in Highly Confined Microenvironments in Mature Dendritic Cells.
Lucie Barbier, Pablo J Sáez, Rafaele Attia, Ana-Maria Lennon-Duménil, Ido Lavi, Matthieu Piel, Pablo Vargas
Frontiers in immunology - 747 - DOI : 10.3389/fimmu.2019.00747 - 2019
Upon infection, mature dendritic cells (mDCs) migrate from peripheral tissue to lymph nodes (LNs) to activate T lymphocytes and initiate the adaptive immune response. This fast and tightly regulated process is tuned by different microenvironmental factors, such as the physical properties of the tissue. Mechanistically, mDCs migration mostly relies on acto-myosin flow and contractility that depend on non-muscular Myosin IIA (MyoII) activity. However, the specific contribution of this molecular motor for mDCs navigation in complex microenvironments has yet to be fully established. Here, 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. Indeed, despite the fact that mDCs speed declined, these cells still migrated through the 3D gels, indicating that this molecular motor has a discrete function during their motility in this irregular microenvironment. Consistently, using microchannels of different sizes, we found that MyoII activity was essential to maintain fast cell speed specifically under strong confinement. Analysis of cell motility through micrometric holes further demonstrated that cell contractility facilitated mDCs passage only over very small gaps. Altogether, this work highlights that high contractility acts as an adaptation mechanism exhibited by mDCs to optimize their motility in restricted landscapes. Hence, MyoII activity ultimately facilitates their navigation in highly confined areas of structurally irregular tissues, contributing to the fine-tuning of their homing to LNs to initiate adaptive immune responses.

400 publications.