Chepizhko Oleksandr, Armengol-Collado Josep-Maria, Alexander Stephanie, Wagena Esther, Weigelin Bettina, Giomi Luca, Friedl Peter, Zapperi Stefano, La Porta Caterina A M
Lakeside Labs GmbH, 9020 Klagenfurt, Austria.
Instituut-Lorentz, Universiteit Leiden, 2300 RA Leiden, The Netherlands.
Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2414009121. doi: 10.1073/pnas.2414009121. Epub 2024 Dec 30.
Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order. We analyze the deformations induced by the cells in the extracellular matrix and find broadly distributed strain bands with a prevalence of compression. A model of active nematic hydrodynamics is able to describe several statistical features of the experimentally observed flow, suggesting that collective cancer cell invasion can be interpreted as a nematic active fluid in the turbulent regime. Our results help elucidate the migration patterns of cancer cells in vivo and provide quantitative guidance for the development of realistic in vitro and in silico models for collective cell migration.
癌细胞的集体迁移通常使用源于活性物质物理学的概念来解释,但实验证据大多局限于体外观察。在这里,我们使用活体多光子显微镜结合皮肤窗口技术和三维定量图像分析,研究注入小鼠深层真皮的转移性癌细胞的集体侵袭。我们观察到一种多细胞但低内聚性的迁移模式,其特征是旋转模式,这些模式自组织成具有向列取向顺序的反平行持久轨迹。我们分析了细胞在细胞外基质中引起的变形,发现应变带广泛分布且以压缩为主。活性向列流体动力学模型能够描述实验观察到的流动的几个统计特征,这表明集体癌细胞侵袭可以解释为湍流状态下的向列活性流体。我们的结果有助于阐明癌细胞在体内的迁移模式,并为开发用于集体细胞迁移的真实体外和计算机模型提供定量指导。