Biology subjects

Duclut, C.

Publications and source records attributed to Duclut, C..

6 recordsLinked to original sources

bioRxiv2026

Fluid transport properties dominate blastocyst expansion over mechanics

Lumens populate most of our organs and their size, which dynamically changes throughout the day and lifetime, can influence their function. During mammalian development, the first lumen appears in the blastocyst. Surface epithelial cells pump ions to build an osmotic gradient that draws water, which inflates the embryo and stretches the epithelium as well as the zona pellucida, an elastic shell protecting the embryo. Blastocyst expansion is not steady and instead undergoes cycles of expansion interrupted by collapses during which the lumen leaks out. Early studies identified the critical role of osmotic pressure difference in regulating the expansion of the blastocyst whereas recent studies proposed that mechanical stresses would set the size of the embryo. However, the relative contributions of osmotic and mechanical stresses to lumen expansion dynamics remain unclear. Here, we investigate this using microfluidics, biophysics, machine learning and modelling on mouse embryos. Breaking down the expansion dynamics of mouse embryos, we discovered that fluid pumping rate accelerates, compensating for the increased frequency of collapses interrupting episodes of expansion. We reasoned that fluid transport could be rate limited by osmotic pumping, water permeability and/or mechanical constraints. Removing the mechanical constraint from the zona pellucida only marginally affected these expansion dynamics. Forcing fluid exchange with osmotic shocks we measured that water permeability is large enough not to restrict fluid accumulation rates. Finally, we estimate ion pumping for mouse blastocysts and interfere with it using inhibitors to measure how it quantitatively sets blastocyst expansion rates. Together, we propose that osmotic pressure differences, regulated by fluid transport properties, dominate over mechanical stresses in controlling blastocyst expansion dynamics.

developmental biology↗

bioRxiv2026

Self-centering steady-state flows emerge in confined actomyosin networks

The actin cytoskeleton drives shape changes and transport in cells and supports mechanical signal transmission. However, how cells control and use active cytoskeletal flows at the mesoscale is not well understood. We reconstituted an active cytoskeleton in water-in-oil emulsion droplets of Xenopus laevis egg extract and observed, above a critical droplet size, the emergence of a 3D radially convergent steady-state flow of polymeric actin, maintained by continuous actin turnover. The flow condensed lipid-rich cellular debris into a centered inclusion. Steady-state F-actin density and flow velocity profiles roughly collapse onto scale-invariant master curves. This behavior can be explained by a physical model representing the network as an isotropic active viscous fluid with a percolation threshold. The contracting network behaves as an active swimmer with complex internal dynamics that centers itself and the central inclusion inside the droplets without physical boundary attachment. Active contraction, crosslinking and polymerization dynamics in an actin network can thus generate cell-scale flow patterns that sense the confining geometry and external signals and exert forces that are likely sufficient to move and localize organelles in cells.

biophysics↗

bioRxiv2025

Regulation of epithelial tissue homeostasis by active trans-epithelial transport

Epithelia are intricate tissues whose function is intimately linked to mechanics. While mechanobiology has primarily focused on factors such as cell-generated contractility and mechanical properties of extracellular matrix (ECM), a novel mechanobiological paradigm highlights the role of osmotic and mechanical pressures in shaping epithelial tissues. In our study, we developed an in vitro model of cell coated micro-sized hydrogel spheres (MHSs) which allows to decipher the interplay between cellular activities and tissue mechanics. Drastic, isotropic MHS compressions were observed once the epithelia reached confluence. Further studies revealed that the compression was a process independent of cell contractility but rather regulated by active transepithelial fluid flow. Compressive stresses of about 7 kPa are generated by such an active hydraulic mechanism. Tissue homeostasis is then maintained by a fine balance between cell proliferation and extrusion. Our findings demonstrate the critical role of fluid transport in generating mechanical forces within epithelial tissues. Supported by a theoretical mechano-hydraulic model, a mechanistic framework for understanding the intricate interplay between cellular processes and tissue mechanics was established. These results challenge traditional views of epithelial tissue mechanics, emphasizing the pivotal influence of osmotic and mechanical pressures in shaping tissues. We anticipate that this study will advance the understanding of epithelial tissue development, the maintenance of homeostasis, and the mechanisms underlying pathological conditions. Significance StatementEpithelial tissues are vital for many bodily functions, but their mechanics remain poorly understood. Our study uncovers a novel mechanism by which epithelial cells generate mechanical stress, not through traditional cell contractility, but by actively pumping ions and water across their membranes. Using a model of micro-sized hydrogel spheres (MHSs) coated with epithelial cells, we demonstrate that epithelial cells actively transport fluid across the tissue to compress the MHSs. This facilitates the establishment of tissue homeostasis, which is further maintained by a balanced cell proliferation and extrusion rate. Supported by a theoretical model, our findings highlight the overlooked role of fluid transport in tissue mechanics, offering new insights into how epithelial tissues develop, maintain stability, and respond to disease.

cell biology↗

bioRxiv2025

Injury-induced electrochemical coupling triggers regenerative cell proliferation

Organ injury triggers non-neuronal electric currents essential for regeneration. Yet, the mechanisms by which electrical signals are generated, sensed and transmitted upon damage to promote organ growth remain unclear. Here, we uncover that organ regeneration relies on dynamic electrochemical coupling between tissue-wide depolarization and intracellular proliferative signalling. By sub-second live imaging of injured zebrafish larval fins, we identify events across timescales: a millisecond tissue depolarization gradient, followed by seconds-persistent intracellular Calcium responses. Subsequently within one hour, Voltage Sensing Phosphatase activity translates depolarisation into proliferation. Connecting these timescales with an electro-diffusive model showed that ionic fluxes and electric potential become coupled in the fins interstitial space, enabling organ-wide signal spreading. Our work reveals the coupling between fast electrical signals and slower intracellular signalling, ensuring organ regeneration.

biophysics↗

bioRxiv2022

Core PCP mutations affect short time mechanical properties but not tissue morphogenesis in the Drosophila pupal wing

How morphogenetic movements are robustly coordinated in space and time is a fundamental open question in biology. We study this question using the wing of Drosophila melanogaster, an epithelial tissue that undergoes large-scale tissue flows during pupal stages. We showed previously (Etournay et al., 2015) that pupal wing morphogenesis involves both cellular behaviors that allow relaxation of mechanical tissue stress, as well as cellular behaviors that appear to be actively patterned. The core planar cell polarity (PCP) pathway influences morphogenetic cell movements in many other contexts, which suggests that it could globally pattern active cellular behaviors during pupal wing morphogenesis. We show here, however, that this is not the case: there is no significant phenotype on the cellular dynamics underlying pupal morphogenesis in mutants of core PCP. Furthermore, using laser ablation experiments, coupled with a rheological model to describe the dynamics of the response to laser ablation, we conclude that while core PCP mutations affect the fast timescale response to laser ablation, they do not affect overall tissue mechanics. In conclusion, our work shows that cellular dynamics and tissue shape changes during Drosophila pupal wing morphogenesis are independent of one potential chemical guiding cue, core PCP.

developmental biology↗

bioRxiv2022

Emergent chirality in active solid rotation of pancreas spheres

Collective cell dynamics play a crucial role in many developmental and physiological contexts. While two-dimensional (2D) cell migration has been widely studied, how three-dimensional (3D) geometry and topology interplay with collective cell behavior to determine dynamics and functions remains an open question. In this work, we elucidate the biophysical mechanism underlying rotation in spherical tissues, a phenomenon widely reported both in vivo and in vitro. Using murine pancreas-derived organoids as a model system, we find that epithelial spheres exhibit persistent rotation, rotational axis drift and rotation arrest. Using a 3D vertex model, we demonstrate how the interplay between traction force and polarity alignment can account for these distinct rotational dynamics. Furthermore, our analysis shows that the spherical tissue rotates as an active solid and exhibits spontaneous chiral symmetry breaking. Using a continuum model, we demonstrate how the types and location of topological defects in the polarity field underlie this symmetry breaking process. Altogether, our work shows that tissue chirality can arise via topological defects in the pattern of cell traction forces, with potential implications for left-right symmetry breaking processes in morphogenetic events.

biophysics↗