Institute of Biomechanics and Medical Engineering, Applied Mechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, People's Republic of China.
Department of Physics, Northeastern University, Boston, MA 02115, USA.
J R Soc Interface. 2019 Jul 26;16(156):20190258. doi: 10.1098/rsif.2019.0258. Epub 2019 Jul 31.
Migrating cells constantly experience geometrical confinements in vivo, as exemplified by cancer invasion and embryo development. In this paper, we investigate how intrinsic cellular properties and extrinsic channel confinements jointly regulate the two-dimensional migratory dynamics of collective cells. We find that besides external confinement, active cell motility and cell crowdedness also shape the migration modes of collective cells. Furthermore, the effects of active cell motility, cell crowdedness and confinement size on collective cell migration can be integrated into a unified dimensionless parameter, defined as the cellular motility number (CMN), which mirrors the competition between active motile force and passive elastic restoring force of cells. A low CMN favours laminar-like cell flows, while a high CMN destabilizes cell motions, resulting in a series of mode transitions from a laminar phase to an ordered vortex chain, and further to a mesoscale turbulent phase. These findings not only explain recent experiments but also predict dynamic behaviours of cell collectives, such as the existence of an ordered vortex chain mode and the mode selection under non-straight confinements, which are experimentally testable across different epithelial cell lines.
细胞在体内不断经历几何约束,例如癌症侵袭和胚胎发育。本文研究了内在细胞特性和外在通道约束如何共同调节群体细胞的二维迁移动力学。我们发现,除了外部约束外,细胞的主动迁移和细胞拥挤程度也会影响群体细胞的迁移模式。此外,细胞的主动迁移能力、细胞拥挤程度和约束大小对群体细胞迁移的影响可以整合到一个统一的无量纲参数中,即细胞迁移数(CMN),它反映了细胞主动迁移力和被动弹性回复力之间的竞争。低 CMN 有利于类层流细胞流动,而高 CMN 会破坏细胞运动,导致从层流相到有序涡链相,再到介观湍流相的一系列模式转变。这些发现不仅解释了最近的实验结果,还预测了细胞群体的动态行为,例如有序涡链模式的存在和非直线约束下的模式选择,这些可以通过不同的上皮细胞系进行实验验证。