Biology subjects

Pieuchot, L.

Publications and source records attributed to Pieuchot, L..

5 recordsLinked to original sources

bioRxiv2026

Nucleus confinement within concave microcavities modulates nuclear morphology, subnuclear dynamics and mechanotransduction in human osteosarcoma cells

Cells dynamically integrate biochemical and mechanical signals arising from their surrounding microenvironment to regulate morphology and behavior. Mechanical cues like matrix stiffness, surface topography, and other physical perturbations modify biophysical signals. Surface topography, particularly curvature regime acts as any important mediator of mechanotransduction by coordinating cytoskeletal organization, focal adhesion dynamics, and nuclear architecture. Curvature response has been demonstrated at broader length scales and influences nucleus shape change, chromatin organization, and gene regulation, positioning the nucleus as an active mechanosensitive hub. Bone tissue consists of a curvature-rich microenvironment defined by a trabecular architecture at tissue scale and by resorption cavities such as Howships lacunae at cellular scale. While these geometries are essential for homeostasis, their role in pathological context remains poorly understood. Osteosarcoma develops within this mechanically complex multiscale architecture, but how bone-inspired curvature regulates nuclear behavior and signaling in osteosarcoma cells remains unclear. Here, we engineered three-dimensional (3D) concave hemispherical substrates that recapitulate nucleus-scale bone micro-curvature and assessed their effects on human SaOS-2 osteosarcoma cells. In comparison with flat surfaces, concave confinement resulted in pronounced nuclear rounding and softening, accompanied by Lamin A/C reorganization and increased heterochromatin compaction marked by H3K9me3. Curvature-driven nuclear remodeling selectively modulated Hippo pathway main effectors YAP/TAZ without activating NF-{kappa}B mediated canonical inflammatory responses. Furthermore, cells maintained overall viability without elevated pathological DNA damage or apoptotic signaling, suggesting an adaptive, damage-tolerant nuclear response. Overall, these findings indicate nucleus-scale curvature as a critical regulator within the bone microenvironment that governs nuclear modelling and mechanosensitive signaling in osteosarcoma cells. Incorporating physiologically relevant geometry into in vitro models establishes new insight into cancer microenvironment crosstalk and highlights nuclear interior and outer architecture as a key regulator of tumor cell behavior.

cell biology↗

bioRxiv2024

Rapid Prototyping of 3D Microstructures: A Simplified Grayscale Lithography Encoding Method Using Blender

The democratization of fabrication equipment has spurred recent interest in maskless grayscale lithography for both 2D and 3D microfabrication. However, the design of suitable template images remains a challenge. This work presents a simplified method for encoding 3D objects into grayscale image files optimized for grayscale lithography. Leveraging the widely used, open-source 3D modeling software Blender, we developed a robust approach to convert geometric heights into grayscale levels and generate image files through top-view rendering. Our method accurately reproduced the overall shape of simple structures like stairs and ramps compared to the original designs. We extended this approach to complex 3D sinusoidal surfaces, achieving similar results. Given the increasing accessibility and user-friendliness of digital rendering tools, this study offers a promising strategy for rapid prototyping of initial designs with minimal effort.

bioengineering↗

bioRxiv2024

Biomimetic Virus-Like Particles to control cell functions

Biomimetic cues from the extracellular matrix (ECM) are essential for optimizing cell microenvironments and biomaterials. While native ECM proteins or synthetic peptides offer potential solutions, challenges such as production cost, solubility, and conformational stability limit their use. Here, we present the development of virus-like particles (VLPs) derived from the AP205 RNA phage displaying peptides from key ECM proteins and evaluate their biological activity in a variety of assays. We show that our engineered VLPs can effectively stimulate cell adhesion, migration, proliferation and differentiation. By comparing focal adhesions formed by RGD VLPs with their parent protein, fibronectin, we elucidate both similarities and differences in cell interactions. In addition, we construct heterodimeric particles co-expressing RGD with differentiation peptides and demonstrate retention of bioactivity in a multi-peptide context. This study establishes AP205 VLPs as versatile nanoscale platforms capable of tuning cell functions, with promising applications in nanomedicine and biomaterials. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/612851v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@191b2c2org.highwire.dtl.DTLVardef@6edf5corg.highwire.dtl.DTLVardef@10a134aorg.highwire.dtl.DTLVardef@7864ef_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

bioengineering↗

bioRxiv2024

Mechano-metabolism of adherent cells in 2D and 3D microenvironments

Cells dynamically regulate their morphology, contractility, and metabolism in response to the mechano-chemical properties of their microenvironment. Here, we show matrix stiffness and ligand density jointly govern the bioenergetics of contractile cells through a nonequilibrium active chemo-mechanical model built around a newly introduced cellular metabolic potential. This concept links ATP hydrolysis to mechanosensitive signaling, quantifies the energetic cost of stress fiber assembly, and determines mechanically stable states. The metabolic potential enables quantitative prediction of cell contractility, morphology, and ATP consumption in different stiffness 2D and 3D environments, and we find quantitative agreement with experimental measurements in MDA-MB-231 breast cancer cells. The model further predicts activation of AMPK accompanies increased energetic demands in stiffer microenvironments which we experimentally validate and correlate with increased mitochondrial membrane potential, glucose uptake, and intracellular ATP levels. Together, these findings establish a predictive quantitative framework unifying mechanosensitive control of cell shape and contractility with the metabolic pathways sustaining cellular function across diverse mechanical environments. TeaserMatrix stiffness reshapes the cellular energy budget, driving metabolic adaptation to mechanical demand.

biophysics↗

bioRxiv2019

Actomyosin, vimentin and LINC complex pull on osteosarcoma nuclei to deform on micropillar topography

Cell deformation occurs in many critical biological processes, including cell extravasation during immune response and cancer metastasis. These cells deform the nucleus, its largest and stiffest organelle, while passing through narrow constrictions in vivo and the underlying mechanisms still remain elusive. It is unclear which biochemical actors are responsible and whether the nucleus is pushed or pulled (or both) during deformation. Herein we use an easily-tunable poly-L-lactic acid micropillar topography, mimicking in vivo constrictions to determine the mechanisms responsible for nucleus deformation. Using biochemical tools, we determine that actomyosin contractility, vimentin and nucleo-cytoskeletal connections play essential roles in nuclear deformation, but not A-type lamins. We chemically tune the adhesiveness of the micropillars to show that pulling forces are predominantly responsible for the deformation of the nucleus. We confirm these results using an in silico cell model and propose a comprehensive mechanism for cellular and nuclear deformation during confinement. These results indicate that microstructured biomaterials are extremely versatile tools to understand how forces are exerted in biological systems and can be useful to dissect and mimic complex in vivo behaviour.

cell biology↗