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Dedenon, M.

Publications and source records attributed to Dedenon, M..

3 recordsLinked to original sources

Nematic order in cellular tissues: a standardized framework and anomalous defect dynamics

Cellular monolayers often exhibit orientational order, with nematic alignment of cell shape and cytoskeletal structures governing tissue-scale collective dynamics. Despite extensive studies, a unified analysis framework for characterizing active nematics in living systems remains partial, and key discrepancies with theory persist. Here, we present a systematic and comparative analysis of nematic order and tissue flow dynamics across twelve distinct cell types. We quantify the impact of analysis parameters and provide data-driven guidelines to improve reproducibility and cross-study comparability. Across all nematic systems, we uncover remarkably consistent static properties, supporting the universality of nematic behavior in living tissues. By combining orientation-field analysis with velocity-field measurements and numerical simulations, we show that all examined systems display contractile active nematic signatures, with characteristic flow structures around topological defects. However, direct tracking of individual defects reveals subdiffusive dynamics, in stark contrast with the superdiffusive, self-propelled motion predicted by the hydrodynamic theory of active nematics. Our results establish a standardized framework for nematic analysis in biological systems and highlight fundamental limitations of current active nematic models in describing defect dynamics in living tissues.

biophysics↗

Friction-induced budding of a cancer cell monolayer

The environment surrounding a tumor plays a crucial role in cancer cell dissemination. Within this microenvironment, cancer-associated fibroblasts (CAFs) generate compressive forces and actively remodel tumors. Using in vitro circular clusters of cancer cell monolayers surrounded by CAFs, we generate structures that are reminiscent of multicellular buds observed in vivo for colo-rectal cancer. A supracellular contractile ring spontaneously assembles at the inner edge of the CAF monolayer and drives its closure on top of the cancer cells through a purse-string mechanism. The frictional shear stress exerted by CAFs triggers multilayering of cancer cells, followed by the emergence of a multicellular bud constricted by the CAF ring. To explain this observation, we developed a theoretical model based on continuum mechanics. This model outlines the early transformations in the shape of cancer cell monolayer and links the layering of cells to a general criterion involving height deformation. It identifies the specific physical conditions that favors budding, and reproduces the observed dependence of the budding probability and bud sizes with the diameter of the cancer cell cluster. Our findings highlight the importance of active mechanical interactions between the tumor and its micro-environment on aggressive modes of cancer invasion.

biophysics↗

Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.

cell biology↗