协调的牵引力增加了细胞单层中集体移动包的大小
Coordinated tractions increase the size of a collectively moving pack in a cell monolayer
摘要:
上皮单层中的细胞与它们的邻居协调运动,从而产生跨越多个细胞直径的大小的集体移动包。然而,控制包装尺寸的物理机制仍不清楚。一个潜在的机制来自于假设细胞基质牵引力持续一定的时间尺度:随着足够长的持续时间,集体细胞包出现。为了验证这一假设,我们测量了每个细胞的速度和净牵引力。数据显示,除了具有一定的时间持久性之外,牵引力在空间上是相关的,这表明细胞与它们的邻居协调,以在同一方向上施加牵引力。肌动球蛋白收缩的化学抑制剂和激活剂被用来确定改变牵引持续性和对齐的影响。数值模拟的基础上的自推进Voronoi模型,增强,包括牵引持久性和对齐和校准对实验数据,匹配的实验测量包的大小。该模型确定,如果相邻单元之间没有牵引力对齐,则集体包的大小将大大小于实验中观察到的大小。因此,结合实验和一个简单的力学模型,这项研究证实了长期以来的假设,牵引持久性,并增加了邻居之间的牵引对齐的概念。持久性和排列是控制集体移动的细胞群大小的两个因素。
英文摘要:
Cells in an epithelial monolayer coordinate motion with their neighbors giving rise to collectively moving packs of sizes spanning multiple cell diameters. The physical mechanism controlling the pack size, however, remains unclear. A potential mechanism comes from assuming that cell-substrate traction forces persist over some time scale: with large enough persistence time, collective cell packs emerge. To test this hypothesis, we measured the velocity and net traction of each cell. The data showed that in addition to having some temporal persistence, tractions were spatially correlated, suggesting that cells coordinate with their neighbors to apply tractions in the same direction. Chemical inhibitors and activators of actomyosin contraction were used to determine effects of altering the traction persistence and alignment. Numerical simulations based on the self-propelled Voronoi model, augmented to include both traction persistence and alignment and calibrated against the experimental data, matched the experimentally measured pack size. The model identified that if there were no alignment of traction between neighboring cells, the size of the collective pack would be substantially smaller than observed in the experiments. Hence, combining experiments and a simple mechanical model, this study confirms the long-standing assumption of traction persistence and adds the notion of traction alignment between neighbors. Together, persistence and alignment are two factors controlling the size of a collectively moving cell pack.
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