Glass-like dynamics of collective cell migration
Glass-like dynamics of collective cell migration
复制标题
DOI：
10.1073/pnas.1010059108
复制
发表时间：
2011-03-22
影响因子：
11.1
通讯作者：
Weitz, David A.
中科院分区：
文献类型：
--
作者：
Angelini, Thomas E.;Hannezo, Edouard;Weitz, David A.
组织中的集体细胞迁移发生在整个胚胎发育、伤口愈合和癌性肿瘤侵袭过程中，但最详细的细胞迁移知识来自单细胞研究。当单细胞迁移时，细胞体的形状通过延伸、粘附和收缩的循环过程而剧烈波动，并伴随着迁移方向的不稳定变化。在汇合的细胞层内，这种亚细胞运动必须在相邻细胞之间耦合，但这些亚细胞运动对集体迁移的影响尚不清楚。在这里，我们研究汇合的上皮细胞片内的运动，同时测量集体迁移和亚细胞运动，涵盖广泛的长度尺度、时间尺度和细胞密度。在大长度尺度和时间尺度上，集体迁移随着细胞密度的增加而减慢，但最快的细胞在大型多细胞群体中移动，其规模随着细胞密度的增加而增长。这种行为与颗粒系统中发现的动态异质性有一个有趣的类比，因为颗粒系统变得更加拥挤并接近玻璃化转变。此外，我们发现细胞层内短波长运动的自扩散性逐渐减弱，并且与协作细胞形状波动相关的状态振动密度峰值不断增加。这两个观察结果也有趣地让人想起玻璃化转变。因此，这些结果在汇合层内的细胞运动与接近玻璃化转变的过冷胶体和分子流体的动力学之间提供了广泛且具有启发性的类比。
Collective cell migration in tissues occurs throughout embryonic development, during wound healing, and in cancerous tumor invasion, yet most detailed knowledge of cell migration comes from single-cell studies. As single cells migrate, the shape of the cell body fluctuates dramatically through cyclic processes of extension, adhesion, and retraction, accompanied by erratic changes in migration direction. Within confluent cell layers, such subcellular motions must be coupled between neighbors, yet the influence of these subcellular motions on collective migration is not known. Here we study motion within a confluent epithelial cell sheet, simultaneously measuring collective migration and subcellular motions, covering a broad range of length scales, time scales, and cell densities. At large length scales and time scales collective migration slows as cell density rises, yet the fastest cells move in large, multicell groups whose scale grows with increasing cell density. This behavior has an intriguing analogy to dynamic heterogeneities found in particulate systems as they become more crowded and approach a glass transition. In addition we find a diminishing self-diffusivity of short-wavelength motions within the cell layer, and growing peaks in the vibrational density of states associated with cooperative cell-shape fluctuations. Both of these observations are also intriguingly reminiscent of a glass transition. Thus, these results provide a broad and suggestive analogy between cell motion within a confluent layer and the dynamics of supercooled colloidal and molecular fluids approaching a glass transition.