Biology subjects

Terriac, E.

Publications and source records attributed to Terriac, E..

10 recordsLinked to original sources

bioRxiv2025

Intratumoral Heterogeneity of Vimentin Modulates Nuclear Mechanotransduction, DNA Damage Response and Cancer Cell Survival

Vimentin, a major intermediate filament protein, is essential for maintaining cellular integrity and regulating cytoskeletal dynamics. Its upregulation is a hallmark of epithelial-to-mesenchymal transition (EMT), a process that enhances cancer cell migration, invasion, and metastatic potential. However, single-cell transcriptomic analyses of glioblastoma, the most common and aggressive primary brain tumor, reveal that vimentin expression exhibits significant intratumoral heterogeneity, reflecting diverse cellular subpopulations that may contribute to tumor plasticity, therapy resistance, and disease progression. Here, we show that the absence of vimentin alters nuclear mechanotransduction in response to compression, leading to chromatin remodelling and profound changes in gene expression in cancer cells. Remarkably, we demonstrate that external compressive forces, akin to vimentin deficiency, disrupt DNA damage response pathways. This impairment compromises DNA damage sensing and repair, bypassing DNA damage checkpoints and apoptosis. Consequently, vimentin-negative tumor cells exhibit increased survival in response to physical stress and DNA damage, potentially driving radioresistance and further amplifying intratumoral heterogeneity.

cancer biology↗

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

Amoeboid Cell Migration through Regular Arrays of Micropillars under Confinement

Migrating cells often encounter a wide variety of topographic features--including the presence of obstacles--when navigating through crowded biological environments. Unravelling the impact of topography and crowding on the dynamics of cells is key to better understand many essential physiological processes such as the immune response. We study how migration and search efficiency of HL-60 cells differentiated into neutrophils in quasi two-dimensional environments are influenced by the lateral and vertical confinement and spatial arrangement of obstacles. A microfluidic device is designed to track the cells in confining geometries between two parallel plates with distance h, in which identical micropillars are arranged in regular pillar forests. We find that at each cell-pillar contact event, the cell spends a finite time near the pillar surface, which is independent of the height h and the interpillar spacing e. At low pillar density regime, the directional persistence of cells reduces with decreasing h or e, influencing their diffusivity and first-passage properties. The dynamics is strikingly different at high pillar density regime, where the cells are in simultaneous contact with more than one pillar; the cell velocity and persistence are distinctly higher compared to dilute pillar configurations with the same h. Our simulations reveal that the interplay between cell persistence and cell-pillar interactions can dramatically affect cell diffusivity and, thus, its first-passage properties.

biophysics↗

bioRxiv2021

The role of actin and myosin II in the cell cortex of adhered and suspended cells

Adhesion induces dramatic morphological and mechanical changes to cells, which are reflected by changes to the actin cortex. Among the many different proteins involved in this sub-membranous layer, motor proteins (e.g., nonmuscle myosin II [NMII]) and actin nucleators (e.g., Arp2/3, formins) are known to have significant influences on its dynamics and structure. The different roles of NMII, Arp2/3, and formins in the dynamics, structure, and mechanics of the actin cortex depend on the adhesion state of the cell. In this study, we unravel the interplay between the dynamics, structure, and mechanics of the actin cortex in adhered cells and in cells in suspension. We show that treatments with extrinsic cellular perturbants lead to alterations of all three properties that are correlated. However, intrinsic actin cortex variations between different cell adhesion states lead to unexpected correlations. Surprisingly, we find that NMII minifilaments have a minor influence on the actin cortex. Using new microscopy techniques, we show that NMII minifilaments are not localized within the actin cortex, as previously thought, but concentrated in a layer beneath it. Our treatments affecting Arp2/3 and formin reveal correlations between the actin cortex characteristics. Our data build towards a comprehensive understanding of the actin cortex. This understanding allows the prediction and control of cortical changes, which is essential for the study of general cellular processes, such as cell migration, metastasis, and differentiation.

biophysics↗

bioRxiv2021

A novel universal algorithm for filament network tracing and cytoskeleton analysis

The rapid development of advanced microscopy techniques over recent decades has significantly increased the quality of imaging and our understanding of subcellular structures, such as the organization of the filaments of the cytoskeleton using fluorescence and electron microscopy. However, these recent improvements in imaging techniques have not been matched by similar development of techniques for computational analysis of the images of filament networks that can now be obtained. Hence, for a wide range of applications, reliable computational analysis of such two-dimensional (2D) methods remains challenging. Here, we present a new algorithm for tracing of filament networks. This software can extract many important parameters from grayscale images of filament networks, including the Mesh Hole Size, and Filament Length and Connectivity (also known as Coordination Number. In addition, the method allows sub-networks to be distinguished in 2D images using intensity thresholding. We show that the algorithm can be used to analyze images of cytoskeleton networks obtained using different advanced microscopy methods. We have thus developed a new improved method for computational analysis of 2D images of filamentous networks that has wide applications for existing imaging techniques. The algorithm is available as open-source software.

biophysics↗

bioRxiv2020

Vimentin provides target search efficiency and mechanical resilience for dendritic cell migration

Dendritic cells use amoeboid migration to pass through confined tissues to reach the lymph nodes, and this homing function is crucial for immune responses. The underlying mechanisms for this type of migration remain unknown. As vimentin intermediate filaments regulate adhesion-dependent migration, we analyzed whether they have a similar effect on amoeboid migration. We show that lack of vimentin impairs amoeboid migration in vitro in confined environments, and blocks lymph-node homing in mice in vivo. Importantly, we show that vimentin-deficient dendritic cells have a lower coupling factor between cell speed and persistence and reduced target search efficiency (e.g., finding a pathogen, or another cell). These data show that the characteristics of vimentin in its dynamic regulation of cell stiffness and load-bearing, and also elastic capacity, appear to explain the coupling between their migratory ability and search efficiency. Taken together, these data show that vimentin provides the specific mechano-dynamics required for dendritic cell migration and for efficient target searching. Summary statementVimentin contributes to the mechanical stiffness of cells required for amoeboid cell migration through confined spaces, and improves cell-search efficiency. Vimentin-deficient cells migrate more slowly and their migration speed is less coupled to persistence compared to control cells.

biophysics↗

bioRxiv2020

Highly coordinated mechanical motion mediated by the microtubule cytoskeletonis a pivotal element of de-novo symmetry breaking in hydraspheroids

The establishment of polarity in cells and tissues is one of the first steps in multicellular development. The eternal embryo hydra can completely regenerate from a disorganized cell cluster or a small fragment of tissue of about 10, 000 cells. During regeneration, the cells first form a hollow cell spheroid, which then undergoes de-novo symmetry breaking to irreversibly polarize. Here, we address the symmetry-related shape changes. Prior to axis establishment, the spheroid of regenerating cells presents inflation oscillations on several timescales that are isotropic in space. There are transient periods of fluctuations in defined arbitrary directions, until these undergo a clearly identified, irreversible transition to directed fluctuations along the future main axis of the regenerating hydra. Stabilized cytosolic actin structures disappear during the de-novo polarization, while polymerized microtubules remain. In our observations applied drugs that depolymerize actin filaments accelerate the symmetry breaking process, while drug-stabilized actin filaments prevent it. Nocodazole-depolymerized microtubules prevent symmetry breaking, but regeneration can be rescued by the microtubule-stabilizing drug paclitaxel at concentrations where microtubular structures start to reappear. We discuss the possibility that mechanical fluctuations induce the orientation and position of microtubules, which contribute to {beta}-catenin nuclear translocation, to increase the organizer-forming-potential of the cells. Our data suggest that in regenerating hydra spheroids, microtubules play a pivotal role in the cooperative polarization process of the self-organizing hydra spheroid.

biophysics↗

bioRxiv2020

Scanning electron microscopy preparation and analysis of the cell cortex ultrastructure

The cellular cortex is an approximately 200-nm-thick actin network that lies just beneath the cell membrane. It is responsible for the mechanical properties of cells, and as such, it is involved in many cellular processes, including cell migration and cellular interactions with the environment. To develop a clear view of this dense structure, high-resolution imaging is essential. As one such technique, electron microscopy, involves complex sample preparation procedures. The final drying of these samples has significant influence on potential artifacts, like cell shrinkage and the formation of artifactual holes in the actin cortex. In this study, we compared the three most used final sample drying procedures: critical-point drying (CPD), CPD with lens tissue (CPD-LT), and hexamethyldisilazane drying. We show that both hexamethyldisilazane and CPD-LT lead to fewer artifactual mesh holes within the actin cortex than CPD. Moreover, CPD-LT leads to significant reduction in cell height compared to hexamethyldisilazane and CPD. We conclude that the final drying procedure should be chosen according to the reduction in cell height, and so CPD-LT, or according to the spatial separation of the single layers of the actin cortex, and so hexamethyldisilazane.

biophysics↗

bioRxiv2019

Vimentin provides the mechanical resilience required for amoeboid migration and protection of the nucleus.

Dendritic cells use amoeboid migration through constricted passages to reach the lymph nodes, and this homing function is crucial for immune responses. Amoeboid migration requires mechanical resilience, however, the underlying molecular mechanisms for this type of migration remain unknown. Because vimentin intermediate filaments (IFs) and microfilaments regulate adhesion-dependent migration in a bidirectional manner, we analyzed if they exert a similar control on amoeboid migration. Vimentin was required for cellular resilience, via a joint interaction between vimentin IFs and F-actin. Reduced actin mobility in the cell cortex of vimentin-reduced cells indicated that vimentin promotes Factin subunit exchange and dynamics. These mechano-dynamic alterations in vimentin-deficient dendritic cells impaired amoeboid migration in confined environments in vitro and blocked lymph node homing in mouse experiments in vivo. Correct nuclear positioning is important in confined amoeboid migration both to minimize resistance and to avoid DNA damage. Vimentin-deficiency also led to DNA double strand breaks in the compressed dendritic cells, pointing to a role of vimentin in nuclear positioning. Together, these observations show that vimentin IF-microfilament interactions provide both the specific mechano-dynamics required for dendritic cell migration and the protection the genome needs in compressed spaces.\n\nSummary statementVimentin -- in joint action with actin -- mediates the mechanical stiffness of cells required for amoeboid cell migration through confined spaces and protects the nucleus from DNA damage.

biophysics↗

bioRxiv2017

An adder behavior in mammalian cells achieves size control by modulation of growth rate and cell cycle duration

Despite decades of research, it remains unclear how mammalian cell growth varies with cell size and across the cell division cycle to maintain size control. Answers have been limited by the difficulty of directly measuring growth at the single cell level. Here we report direct measurement of single cell volumes over complete cell division cycles. The volume added across the cell cycle was independent of cell birth size, a size homeostasis behavior called \"adder\". Single-cell growth curves revealed that the homeostatic behavior relied on adaptation of G1 duration as well as growth rate modulations. We developed a general mathematical framework that characterizes size homeostasis behaviors. Applying it on datasets ranging from bacteria to mammalian cells revealed that a near-adder is the most common type of size control, but only mammalian cells achieve it using modulation of both cell growth rate and cell-cycle progression.

cell biology↗