Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374, USA.
Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2452-9. doi: 10.1073/pnas.1219937110. Epub 2013 Jan 23.
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.
最近的实验表明，铺展的上皮片层表现出长程运动力的协调，这导致组织中的张力增加，这可能增强细胞分裂和伤口愈合的速度。此外，这些上皮片层的边缘通常显示出指状突起，而大部分通常显示出运动细胞的自发漩涡。为了解释这些实验观察结果，我们提出了一种简单的群体行为机制，其中细胞倾向于将其运动力与速度对齐。在机械组织模拟中实现这一想法，所提出的模型导致有效的铺展，并能够解释在高度无序模式下观察到的运动力的长程对齐，以及整个组织中拉伸应力的积累。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，并表现出在体内常见的铺展组织边缘的波动不稳定性。最后，我们研究了集落铺展速度对重要物理和生物参数的依赖性，并得出了简单的标度关系，表明运动力的协调导致在现实组织参数下伤口愈合过程的改善。
