Biology subjects

Turlier, H.

Publications and source records attributed to Turlier, H..

9 recordsLinked to original sources

bioRxiv2026

Elevated cortical tension triggers precocious ectopic polarization in mammalian oocytes, associated with lower developmental potential.

Oocytes from many organisms polarize early during development, unlike mammalian oocytes. The significance of maintaining this homogeneous state in mammals remains unclear. We show that elevated cortical tension, via increased actomyosin contractility or disrupted cortical architecture, induces precocious cortical polarization mid-meiosis I, with an ectopic actomyosin-rich domain opposite the future division site. This polarization generates directional cytoplasmic flows that displace organelles and the spindle, accelerating its migration and disrupting its orientation. A hydrodynamic model coupling the polarized cortex to a viscous cytoplasm accounts for these rearrangements. Ectopic polarization persists in meiosis II and is associated with mislocalization of fertilization factors, increased fertilization rates and polyspermy, and reduced early embryonic development. A similar morphological signature arises spontaneously in subsets of mouse and human oocytes. These results reveal precocious cortical polarization as a previously unrecognized, mechanically accessible state largely absent from mammalian oocytes, which may contribute to variability in oocyte quality.

cell biology↗

bioRxiv2024

Long range mutual activation establishes Rho and Rac polarity during cell migration

In migrating cells, the GTPase Rac organizes a protrusive front, whereas Rho organizes a contractile back. How these GTPases are appropriately positioned at the opposite poles of migrating cells is unknown. Here we leverage optogenetics, manipulation of cell mechanics, and mathematical modeling to reveal a surprising mechanochemical long-range mutual activation of the front and back polarity programs that complements their well-known local mutual inhibition. Rac-based protrusion stimulates Rho activation at the opposite side of the cell via membrane tension-based activation of mTORC2. Conversely, Rho-based contraction induces cortical-flow-based regulation of phosphoinositide signaling to trigger Rac activation at the opposite side of the cell. We develop a minimal unifying mechanochemical model of the cell to explain how this long-range facilitation complements local inhibition to enable robust Rho and Rac partitioning. We show that this long-range mutual activation of Rac and Rho is conserved in epithelial cells and is also essential for efficient polarity and migration of primary human T cells, indicating the generality of this circuit. Our findings demonstrate that the actin cortex and plasma membrane function as an integrated mechanochemical system for long-range partitioning of Rac and Rho during cell migration and likely other cellular contexts.

cell biology↗

bioRxiv2023

Embryo mechanics cartography: inference of 3D force atlases from fluorescence microscopy

The morphogenesis of tissues and embryos results from a tight interplay between gene expression, biochemical signaling and mechanics. Although sequencing methods allow the generation of cell-resolved spatio-temporal maps of gene expression in developing tissues, creating similar maps of cell mechanics in 3D has remained a real challenge. Exploiting the foam-like geometry of cells in embryos, we propose a robust end-to-end computational method to infer spatiotemporal atlases of cellular forces from fluorescence microscopy images of cell membranes. Our method generates precise 3D meshes of cell geometry and successively predicts relative cell surface tensions and pressures in the tissue. We validate it with 3D foam simulations, study its noise sensitivity, and prove its biological relevance in mouse, ascidian and C. elegans embryos. 3D inference allows us to recover mechanical features identified previously, but also predicts new ones, unveiling potential new insights on the spatiotemporal regulation of cell mechanics in early embryos. Our code is freely available and paves the way for unraveling the unknown mechanochemical feedbacks that control embryo and tissue morphogenesis.

biophysics↗

bioRxiv2023

Reduction of cortical pulling at mitotic entry facilitates aster centration

Although it has been studied for more than a century, the question of how one cell divides into two equal parts is still not fully resolved. Zygotes have provided much of the mechanistic insight into how the mitotic apparatus finds the center of the cell since the centrally-located mitotic apparatus is created from a large sperm aster that forms at the cortex and thus far from the zygote center. Here we show that in ascidians, the sperm aster extends throughout the cytoplasm during interphase yet remains located near the cortex and does not migrate towards the zygote center. It is only at mitotic entry, when the sperm aster has duplicated and the mitotic apparatus is being assembled, that most of the migration and centration occurs. This temporal pattern of centration behavior is mirrored by primate zygotes (including human). The current mechanisms of aster centration include cytoplasmic pulling that scale with microtubule (MT) length, MT pushing against the proximal cortex or MT-based cortical pulling. However, it is not yet known whether and how these 3 mechanisms are coordinated to prevent aster migration during interphase and trigger migration at mitotic entry. By monitoring quantitatively all three mechanisms (cytoplasmic pulling, pushing and cortical pulling) we have discovered that cortical pulling is switched off as the zygote enters mitosis while both cytoplasmic pulling and proximal cortical pushing remain active. Physical simulations could recapitulate both the static and migratory aspects of sperm aster and mitotic apparatus behavior. We therefore surmise that the reduction in cortical pulling at mitotic entry represents a switch that allows proximal cortical pushing forces and cytoplasmic pulling forces to center the nascent mitotic apparatus. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/533625v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@135189dorg.highwire.dtl.DTLVardef@e2ef1dorg.highwire.dtl.DTLVardef@c070f7org.highwire.dtl.DTLVardef@38832f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISperm aster/mitotic apparatus centration occurs at entry into first mitosis C_LIO_LIMT-based cortical pulling is active during interphase and switched off at mitotic entry C_LIO_LILoss of cortical pulling at mitosis entry facilitates centration of the aster C_LIO_LIMT-based cytoplasmic pulling is active during both interphase and mitosis C_LIO_LIAgent-based simulations advocate the need for cytoplasmic pulling, a switch in cortical pulling and a minor role of pushing for aster centration at mitotic entry. C_LI

cell biology↗

bioRxiv2023

Dissecting the subcellular forces sculpting early C. elegans embryos

Embryo shape is determined by individual cell mechanics, intercellular interaction strength, and geometrical constraints. Models based on surface tensions at cell interfaces can predict 3D static cellular arrangements within aggregates. However, predicting the dynamics of such arrangements is challenging due to difficulties in measuring temporal changes in tensions. Here, we characterise the spatiotemporal changes in cellular tensions shaping the early nematode embryo using AFM, live microscopy, and tension inference. Using excoriated embryos, we validate a hybrid inference pipeline that calibrates relative inferred tensions temporally using cortical myosin enrichment and absolute tensions using AFM measurements. Applied to embryos within their native shell, we infer a spatiotemporal map of absolute tensions, revealing that ABa, ABp, and EMS compaction is driven by increased tension at free surfaces, while P2s initial exclusion is due to high tension at intercellular contacts. We uncover a direct and non-affine contribution of cadherins to cell-cell contact tension, comparable to cadherins indirect contribution via actomyosin regulation. HighlightsO_LIP lineage cells have lower cortical tensions than AB lineage cells C_LIO_LIEnrichment of Myosin-II at the cell cortex is a good predictor of cell-medium tension but is not sufficient to determine tension at cell-cell contacts. C_LIO_LIMyosin-informed tension inference allows determination of the spatiotemporal evolution of all surface tensions within the embryo. C_LIO_LIABa, ABp, and EMS compact due to high tensions at their cell-medium interfaces compared to their cell-cell interfaces, while P2 is initially excluded due to high cell-cell contact tensions. C_LIO_LICadherins contribute directly in a non-linear way by reducing cell-cell contact tension by nearly 50%. C_LI Open AccessFor the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

biophysics↗

bioRxiv2022

Actin-driven protrusions generate rapid long-range membrane tension propagation in cells

Membrane tension is thought to be a long-range integrator of cell physiology. This role necessitates effective tension transmission across the cell. However, the field remains strongly divided as to whether cell membranes support or resist tension propagation, in part due to a lack of adequate tools for locally manipulating membrane tension. We overcome these limitations by leveraging optogenetics to generate localized actinbased protrusions while concurrently monitoring the propagation of membrane tension using dual-trap optical tweezers. Surprisingly, actin-driven protrusions elicit rapid global membrane tension propagation with little to no attenuation, while forces applied to the cell membrane only do not. We present a simple unifying mechanical model in which mechanical forces that act on both the membrane and actin cortex drive rapid, robust membrane tension propagation. SummaryMechanical perturbations acting on both actin cortex and plasma membrane drive global membrane tension increase within seconds

cell biology↗

bioRxiv2022

Mechanics of human embryo compaction

The shaping of the human embryo begins with compaction, during which cells come into close contact and form a tighter structure1,2. Assisted reproductive technology (ART) studies suggest that human embryos fail compaction primarily because of defective adhesion3,4. Based on our current understanding of animal morphogenesis5,6, other morphogenetic engines, such as cell contractility, could be involved in shaping the human embryo. However, the molecular, cellular and physical mechanisms driving human embryo morphogenesis remain uncharacterized. Using micropipette aspiration on human embryos donated to research, we have mapped cell surface tensions during compaction. This reveals a 4-fold increase of tension at the cellmedium interface while cell-cell contacts keep a steady tension. Comparison between human and mouse reveals qualitatively similar but quantitively different mechanical strategies, with human embryos being mechanically least efficient. Inhibition of cell contractility and cell-cell adhesion in human embryos reveal that only contractility controls the surface tension responsible for compaction. Interestingly, if both cellular processes are required for compaction, they exhibit distinct mechanical signatures when faulty. Analyzing the mechanical signature of naturally failing embryos, we find evidence that non-compacting embryos or partially compacting embryos with excluded cells have defective contractility. Together, our study reveals that an evolutionarily conserved increase in cell contractility is required to generate the forces driving the first morphogenetic movement shaping the human body.

developmental biology↗

bioRxiv2020

Physics of blastocoel formation by hydro-osmotic lumen coarsening

Fluid-filled biological cavities are ubiquitous, but their collective dynamics has remained largely unexplored from a physical perspective. Based on experimental observations in early embryos, we propose a model where a cavity forms through the coarsening of myriad of pressurized micrometric lumens, that interact by ion and fluid exchanges through the intercellular space. Performing extensive numerical simulations, we find that hydraulic fluxes lead to a self-similar coarsening of lumens in time, characterized by a robust dynamic scaling exponent. The collective dynamics is primarily controlled by hydraulic fluxes, which stem from lumen pressures differences and are dampened by water permeation through the membrane. Passive osmotic heterogeneities play, on the contrary, a minor role on cavity formation but active ion pumping can largely modify the coarsening dynamics: it prevents the lumen network from a collective collapse and gives rise to a novel coalescence-dominated regime exhibiting a distinct scaling law. Interestingly, we prove numerically that spatially biasing ion pumping may be sufficient to position the cavity, suggesting a novel mode of symmetry breaking to control tissue patterning. Providing generic testable predictions, our model forms a comprehensive theoretical basis for hydro-osmotic interaction between biological cavities, that shall find wide applications in embryo and tissue morphogenesis. Author summaryThe formation of a single biological cavity, or lumen, in tissues and embryos has been widely studied experimentally but the collective dynamics of multiple lumens has received much less attention. Here, we focus on a particular type of lumens, which are located at the adhesive side of cells and can therefore interact directly through the intercellular space, as recently observed in the very first stages of embryogenesis. We propose a generic model to describe the hydraulic and osmotic exchanges between lumens themselves, and with the surrounding cellular medium. Lumens are pressurized by a surface tension, which leads naturally to their coarsening into a single final cavity through hydraulic exchanges. With extensive numerical simulations and mean-field theory we predict that such coarsening dynamics follows a robust scaling law, that barely depends on concentration heterogeneities between lumens. On the contrary, active osmotic pumping largely influences the collective dynamics by favoring lumen coalescence and by biasing the position of the final cavity. Our theoretical work highlights the essential role of hydraulic and osmotic flows in morphogenesis.

biophysics↗

bioRxiv2019

Fracking and Ostwald ripening position the lumen of the mouse blastocyst

During mouse preimplantation development, the formation of the blastocoel, a fluid-filled lumen, breaks the radial symmetry of the blastocyst. What controls the formation and positioning of this basolateral lumen remains obscure. We find that accumulation of pressurized fluid fractures cell-cell contacts into hundreds of micron-size lumens. Microlumens eventually discharge their volumes into a single dominant lumen, which we model as a process akin to Ostwald ripening, underlying the coarsening of foams. Using chimeric mutant embryos, we tune the tracking of cell-cell contacts and steer the coarsening of microlumens, allowing us to successfully manipulate the final position of the lumen. We conclude that hydraulic fracture of cell-cell contacts followed by directed coarsening of microlumens sets the first axis of symmetry of the mouse embryo.

developmental biology↗