Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Adv Biol (Weinh). 2023 Oct;7(10):e2300026. doi: 10.1002/adbi.202300026. Epub 2023 Mar 18.
Cells detached and disseminated away from collectively migrating cells are frequently found during tumor invasion at the invasion front, where extracellular matrix (ECM) fibers are parallel to the cell migration direction. However, it remains unclear how anisotropic topography promotes the transition of collective to disseminated cell migration. This study applies a collective cell migration model with and without 800 nm wide aligned nanogrooves parallel, perpendicular, or diagonal to the cell migration direction. After 120 hour migration, MCF7-GFP-H2B-mCherry breast cancer cells display more disseminated cells at the migration front on parallel topography than on other topographies. Notably, a fluid-like collective motion with high vorticity is enhanced at the migration front on parallel topography. Furthermore, high vorticity but not velocity is correlated with disseminated cell numbers on parallel topography. Enhanced collective vortex motion colocalizes with cell monolayer defects where cells extend protrusions into the free space, suggesting that topography-driven cell crawling for defect closure promotes the collective vortex motion. In addition, elongated cell morphology and frequent protrusions induced by topography may further contribute to the collective vortex motion. Overall, a high-vorticity collective motion at the migration front promoted by parallel topography suggests a cause of the transition of collective to disseminated cell migration.
在肿瘤侵袭前沿，从集体迁移细胞中分离和扩散的细胞经常被发现，其中细胞外基质（ECM）纤维与细胞迁移方向平行。然而，目前尚不清楚各向异性地形如何促进集体到弥散细胞迁移的转变。本研究应用了一个具有和不具有 800nm 宽平行纳米槽的集体细胞迁移模型，纳米槽平行、垂直或对角于细胞迁移方向。在 120 小时的迁移后，MCF7-GFP-H2B-mCherry 乳腺癌细胞在平行地形上的迁移前沿显示出更多的弥散细胞。值得注意的是，在平行地形上的迁移前沿，具有高涡度的类液体集体运动得到增强。此外，高涡度而不是速度与平行地形上弥散细胞数量相关。增强的集体涡旋运动与细胞单层缺陷共定位，其中细胞将突起延伸到自由空间，表明地形驱动的细胞爬行以封闭缺陷促进了集体涡旋运动。此外，地形诱导的细长细胞形态和频繁的突起可能进一步促进集体涡旋运动。总的来说，平行地形上迁移前沿的高涡度集体运动表明了从集体到弥散细胞迁移转变的原因。
