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Cells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term “curvotaxis” that enables the cells to respond to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton—the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue. The effect that microscale surface curvature has on cell migration has not been evaluated. Here the authors fabricate sinusoidal 3D surfaces and show that the cell nucleus and cytoskeleton cooperate to guide cells to concave valleys in a process they coin curvotaxis.

Background Endometriosis is a chronic disease characterized by growth of endometrial tissue outside the uterine cavity which could affect 200 million women (The term “woman” is used for convenience. Individuals gendered as man or as nonbinary can also suffer from this disease) worldwide. One of the most common symptoms of endometriosis is pelvic chronic pain associated with fatigue. This pain can cause psychological distress and interpersonal difficulties. As for several chronic diseases, adapted physical activity could help to manage the physical and psychological symptoms. The present study will investigate the effects of a videoconference-based adapted physical activity combined with endometriosis-based education program on quality of life, pain, fatigue, and other psychological symptoms and on physical activity. Methods This multicentric randomized-controlled trial will propose to 200 patients with endometriosis to be part of a trial which includes a 6-month program with 45 min to more than 120 min a week of adapted physical activity and/or 12 sessions of endometriosis-based education program. Effects of the program will be compared to a control group in which patients will be placed on a waiting list. All participants will be followed up 3 and 6 months after the intervention. None of the participants will be blind to the allocated trial arm. The primary outcome measure will be quality of life. Secondary outcomes will include endometriosis-related perceived pain, fatigue, physical activity, and also self-image, stereotypes, motivational variables, perceived support, kinesiophobia, basic psychological need related to physical activity, and physical activity barriers. General linear models and multilevel models will be performed. Predictor, moderator, and mediator variables will be investigated. Discussion This study is one of the first trials to test the effects of a combined adapted physical activity and education program for improving endometriosis symptoms and physical activity. The results will help to improve care for patients with endometriosis. Trial registration ClinicalTrials.gov, NCT05831735 . Date of registration: April 25, 2023

In insects, biogenic amines have been shown to play an important role in olfactory plasticity. In a first attempt to decipher the underlying molecular mechanisms, we report the molecular cloning and precise expression pattern of a newly identified octopamine/tyramine-receptor-encoding gene in the antennae of the noctuid moth Mamestra brassicae (MbraOAR/TAR). A full-length cDNA has been obtained through homology cloning in combination with rapid amplification of cDNA ends/polymerase chain reaction; the deduced protein exhibits high identities with previously identified octopamine/tyramine receptors in other moths. In situ hybridization within the antennae has revealed that MbraOAR/TAR is expressed at the bases of both pheromone-sensitive and non-sensitive olfactory sensilla and in cells with a neurone-like shape. In accordance with previous physiological studies that have revealed a role of biogenic amines in the electrical activity of the receptor neurones, our results suggest that biogenic amines (either octopamine or tyramine) target olfactory receptor neurones to modulate olfactory coding as early as the antennal level.

Although the regulation of epithelial morphogenesis is essential for the formation of tissues and organs in multicellular organisms, little is known about how signalling pathways control cell shape changes in space and time. In the Drosophila ovarian epithelium, the transition from a cuboidal to a squamous shape is accompanied by a wave of cell flattening and by the ordered remodelling of E-cadherin-based adherens junctions. We show that activation of the TGFβ pathway is crucial to determine the timing, the degree and the dynamic of cell flattening. Within these cells, TGFβ signalling controls cell-autonomously the formation of Actin filament and the localisation of activated Myosin II, indicating that internal forces are generated and used to remodel AJ and to promote cytoskeleton rearrangement. Our results also reveal that TGFβ signalling controls Notch activity and that its functions are partly executed through Notch. Thus, we demonstrate that the cells that undergo the cuboidal-to-squamous transition produce active cell-shaping mechanisms, rather than passively flattening in response to a global force generated by the growth of the underlying cells. Thus, our work on TGFβ signalling provides new insights into the mechanisms through which signal transduction cascades orchestrate cell shape changes to generate proper organ structure.

Virus-like particles (VLPs) serve as modular scaffolds for biomaterial surface biofunctionalization, enabling high-density, spatially confined display of ECM-derived peptides.Two strategies were employed: genetic fusion (AP205) and modular SpyTag/SpyCatcher ligation (Mi3).AP205 VLPs displaying RGD supported stable cell adhesion and promoted migration, proliferation, and differentiation of C2C12 cells.SpyTag/SpyCatcher-functionalized Mi3 VLPs with elastin-like polypeptide–the arginine-glycine-aspartic acid (RGD) outperformed fibronectin, enhancing adhesion via flexible, hydrophilic spacers that improve ligand accessibility and signaling.Modular VLP design allows co-display of multiple bioactive cues, enabling complex tissue engineering strategies that closely mimic the native extracellular matrix (ECM).VLPs adsorbed stably on polydimethylsiloxane (PDMS) and titanium without chemical modification and can be produced cost-effectively in Escherichia coli, offering a scalable alternative to native ECM proteins for biomedical applications. Biomaterial surface biofunctionalization refers to the process of modifying a biomaterial’s surface to improve its interaction with biological systems. Controlling cell-material interactions is crucial, but current methods using native extracellular matrix (ECM) proteins, typically derived from human or animal tissue, or synthetic peptides are hampered by limitations such as batch variability, high cost, poor surface adsorption, and limited control over peptide presentation. This study introduces a technology that uses virus-like particles (VLPs) displaying biomimetic ECM-derived peptides. We engineered VLPs to present the RGD motif (arginine-glycine-aspartic acid), a well-established sequence that promotes cell adhesion, using either direct genetic fusion or SpyTag/SpyCatcher ligation, with the latter providing a more versatile conjugation strategy. These VLPs effectively functionalized cell-repellent silicone surfaces, significantly enhancing cell adhesion, migration, proliferation, and differentiation, achieving performance comparable with or exceeding that of native ECM proteins or synthetic RGD peptides. Additionally, the VLP/SpyCatcher particle enabled the co-presentation of multiple bioactive peptides, opening avenues for complex tissue engineering strategies. This tunable system represents a powerful tool for directing cell behavior, with significant potential for advancing nanomedicine and biomaterials development. [Display omitted] The virus-like particle (VLP)-based surface biofunctionalization strategy presented in this study currently reaches a Technology Readiness Level (TRL) of 3–4. This assessment reflects the successful demonstration of the core concept in controlled laboratory conditions, including recombinant production of functionalized VLPs in Escherichia coli, their adsorption onto biomaterial surfaces [polydimethylsiloxane (PDMS) and titanium], and their bioactivity in guiding cell adhesion, proliferation, and differentiation in vitro. The system combines both genetic fusion (AP205) and modular conjugation (SpyTag/SpyCatcher with Mi3) to achieve spatially defined, high-density presentation of bioactive peptides. To progress toward higher TRLs, key challenges include validating long-term stability and bioactivity in more physiologically relevant or mechanically dynamic environments, scaling conjugation workflows, and improving immobilization robustness for real-world use cases. Applications involving full-length proteins or clinical translation may require enhanced purification strategies and regulatory compliance. Importantly, this platform avoids animal-derived components and aligns with standard biosafety frameworks, which simplifies future adoption in biomedical contexts. With further optimization and testing in complex biological models, this technology could move toward TRL 5–6, unlocking applications in regenerative medicine, implant coatings, and high-throughput screening. This study showcases virus-like particles (VLPs) as customizable nanoscale scaffolds for biomaterial surface functionalization. Using modified VLPs, we achieve high density display and confinement of bioactive peptides, offering a modular, animal-free, and cost-effective alternative to native extracellular matrix (ECM) proteins in tissue engineering and regenerative medicine.

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. biorxiv;2024.09.14.612851v1/UFIG1F1ufig1Graphical abstract

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.