Nagle Irène, Richert Alain, Quinteros Michael, Janel Sébastien, Buysschaert Edgar, Luciani Nathalie, Debost Henry, Thevenet Véronique, Wilhelm Claire, Prunier Céline, Lafont Frank, Padilla-Benavides Teresita, Boissan Mathieu, Reffay Myriam
Laboratoire Matière et Systèmes Complexes, UMR 7057, Université Paris Cité and CNRS, Paris, France.
Molecular Biology and Biochemistry Department, Wesleyan University, Middletown, CT, United States.
Front Cell Dev Biol. 2022 Aug 30;10:926322. doi: 10.3389/fcell.2022.926322. eCollection 2022.
Epithelial-mesenchymal transition is associated with migration, invasion, and metastasis. The translation at the tissue scale of these changes has not yet been enlightened while being essential in the understanding of tumor progression. Thus, biophysical tools dedicated to measurements on model tumor systems are needed to reveal the impact of epithelial-mesenchymal transition at the collective cell scale. Herein, using an original biophysical approach based on magnetic nanoparticle insertion inside cells, we formed and flattened multicellular aggregates to explore the consequences of the loss of the metastasis suppressor NME1 on the mechanical properties at the tissue scale. Multicellular spheroids behave as viscoelastic fluids, and their equilibrium shape is driven by surface tension as measured by their deformation upon magnetic field application. In a model of breast tumor cells genetically modified for NME1, we correlated tumor invasion, migration, and adhesion modifications with shape maintenance properties by measuring surface tension and exploring both invasive and migratory potential as well as adhesion characteristics.
上皮-间质转化与迁移、侵袭和转移相关。这些变化在组织尺度上的转化尚未得到阐明,而这对于理解肿瘤进展至关重要。因此,需要专门用于模型肿瘤系统测量的生物物理工具来揭示上皮-间质转化在集体细胞尺度上的影响。在此,我们使用一种基于磁性纳米颗粒插入细胞内部的原始生物物理方法,形成并扁平化多细胞聚集体,以探索转移抑制因子NME1缺失对组织尺度力学性能的影响。多细胞球体表现为粘弹性流体,其平衡形状由表面张力驱动,这可通过施加磁场时的变形来测量。在针对NME1进行基因改造的乳腺肿瘤细胞模型中,我们通过测量表面张力并探究侵袭和迁移潜能以及粘附特性,将肿瘤侵袭、迁移和粘附修饰与形状维持特性相关联。
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