Biology subjects

Deygas, M.

Publications and source records attributed to Deygas, M..

5 recordsLinked to original sources

bioRxiv2026

Spatiotemporal dynamics of hydrogen peroxide during neutrophil swarming in 3D

Neutrophil swarming enables the coordinated recruitment of large numbers of cells to sites of infection. Although reactive oxygen species (ROS) are key mediators of neutrophil function, their dynamics during collective behavior remain poorly defined. Here, we developed a 3D ex vivo swarming system combined with HyPer7-expressing dHL-60 cells to visualize intracellular hydrogen peroxide (H2O2) dynamics in real time at single-cell resolution. This approach enabled us to reliably measure NADPH oxidase 2 (NOX2) activity during neutrophil swarming, revealing dynamic H2O2 production. We show that H2O2 production is spatially confined to cells at the stimulation site and temporally coupled to swarming initiation and distal cell recruitment. ROS production depends on NOX2 activity and calcium signaling but is not required for swarm formation or amplification. Notably, H2O2 accumulation was detected throughout activated cells rather than being restricted to phagosomes, suggesting a broader intracellular oxidative response. Together, these findings reveal a coordinated oxidative program associated with neutrophil swarm initiation and raise the possibility that ROS contribute to signaling functions beyond their established role in phagocytosis.

Cell Biology↗

bioRxiv2025

Torque-based immune cell chemotaxis in complex environments

Directed migration in chemical gradients is crucial to the immune response, yet how immune cells navigate complex tissues remains incompletely understood. Using in vitro migration assays and theoretical modeling, we uncover distinct chemotactic strategies in two key immune cell types: neutrophils and dendritic cells (DCs). DCs actively steer toward chemokine gradients via a deterministic torque-like reorientation, while neutrophils bias movement by modulating angular noise and speed. A quantitative Fokker-Planck framework decomposes these behaviors into deterministic and stochastic components. Cytoskeletal perturbations show that microtubules enable torque-based navigation in DCs in collagen gels, whereas actomyosin contractility is required for noise modulation employed by neutrophils and DCs in 2D confined migration assays. Despite both achieving directed migration, the two strategies result in opposing macroscopic outcomes: torque-driven cells minimize dispersion, while noise-biased migration enhances population spread. These results reveal distinct navigation aligned with immune function and demonstrate that immune cell chemotaxis is tuned by cytoskeletal architecture and environmental context.

biophysics↗

bioRxiv2025

Fast adaptation of Myosin II activity to confinement sustains neutrophil migration in capillaries

As the first responders of the immune system, neutrophils rapidly and abundantly reach inflamed tissues through blood capillaries. The diameter of capillaries can be as narrow as two microns, imposing considerable deformations on neutrophils. Notably, capillary obstruction due to neutrophil retention causes vascular dysfunction and contributes to the pathogenesis of several diseases. However, the cellular mechanisms that allow neutrophils to migrate into small capillaries and to avoid retention remain unknown. In this study, we demonstrate, both in vivo and in vitro, that capillary size does not influence neutrophil migration velocity. During migration into capillaries of different sizes, neutrophils maintain high speed, a phenomenon associated with a global actomyosin cytoskeleton rearrangement in response to confinement strength. In irregular capillaries, neutrophils rapidly adapt their cell contractility via the ROCK-MyoII pathway, which allows them to sustain their migration speed along the vessels despite changes in confinement. At the single cell level, inhibition of ROCK impairs actomyosin cytoskeleton rearrangement and reduces neutrophil migration speed within confined capillaries. At the collective level, ROCK inhibition hampers efficient neutrophil trafficking in a network of small capillaries, resulting in vessel obstruction. These findings reveal a unique capacity of neutrophils to rapidly and dynamically adapt their migration to the confinement strength of capillaries, an ability that might limit vascular dysfunction during inflammation.

cell biology↗

bioRxiv2022

Compressive forces stabilise microtubules in living cells

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 microtubules in vitro have 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.

cell biology↗

bioRxiv2020

HIF2α is a Direct Regulator of Neutrophil Motility

Orchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.

immunology↗