Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing
Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing
复制标题
DOI：
10.1073/pnas.1219937110
复制
发表时间：
2013-02-12
影响因子：
11.1
通讯作者：
Levine, Herbert
中科院分区：
文献类型：
--
作者：
Basan, Markus;Elgeti, Jens;Levine, Herbert
最近的实验表明，铺展的上皮片表现出运动力的长程协调，导致组织中张力的积累，这可能会增强细胞分裂和伤口愈合的速度。此外，这些上皮片的边缘通常显示出手指状突起，而大部分通常显示出活动细胞的自发漩涡。为了解释这些实验观察结果，我们提出了一种简单的聚集型机制，其中细胞倾向于将其运动力与其速度保持一致。在机械组织模拟中实现这一想法，所提出的模型产生了有效的扩散，并且可以解释实验观察到的高度无序模式中运动力的长程排列，以及整个组织中拉应力的积累。我们的模型还定性地再现了实验中报告的漩涡大小和漩涡速度对细胞密度的依赖性，并在体内常见的扩散组织边缘表现出波动不稳定性。最后，我们研究了菌落扩散速度对重要物理和生物参数的依赖性，并推导出简单的标度关系，表明运动力的协调可以改善实际组织参数的伤口愈合过程。
Recent experiments have shown that spreading epithelial sheets exhibit a long-range coordination of motility forces that leads to a buildup of tension in the tissue, which may enhance cell division and the speed of wound healing. Furthermore, the edges of these epithelial sheets commonly show finger-like protrusions whereas the bulk often displays spontaneous swirls of motile cells. To explain these experimental observations, we propose a simple flocking-type mechanism, in which cells tend to align their motility forces with their velocity. Implementing this idea in a mechanical tissue simulation, the proposed model gives rise to efficient spreading and can explain the experimentally observed long-range alignment of motility forces in highly disordered patterns, as well as the buildup of tensile stress throughout the tissue. Our model also qualitatively reproduces the dependence of swirl size and swirl velocity on cell density reported in experiments and exhibits an undulation instability at the edge of the spreading tissue commonly observed in vivo. Finally, we study the dependence of colony spreading speed on important physical and biological parameters and derive simple scaling relations that show that coordination of motility forces leads to an improvement of the wound healing process for realistic tissue parameters.