Califano Joseph P, Reinhart-King Cynthia A
Cornell University, Ithaca, NY 14853, USA.
Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:3343-5. doi: 10.1109/IEMBS.2009.5333194.
While the growth factors and cytokines known to influence angiogenesis and vasculogenesis have garnered widespread attention, less is known about how the mechanical environment affects blood vessel formation and cell assembly. In this study, we investigate the relationship between substrate elasticity, endothelial cell-cell connectivity and traction force generation. We find that on more compliant substrates, endothelial cells self-assemble into network-like structures independently of additional exogenous growth factors or cytokines. These networks form from the assembly of sub-confluent endothelial cells on compliant (E = 200-1000Pa) substrates, and results from both the proliferation and migration of endothelial cells. Interestingly, stabilization of these cell-cell connections and networks requires fibronectin polymerization. Traction Force Microscopy measurements indicate that individual endothelial cells on compliant substrates exert forces which create substrate stains that propagate from the cell edge. We speculate that these strains draw the cells together and initiate self-assembly. Notably, endothelial cell network formation on compliant substrates is dynamic and transient; as cell number and substrate strains increase, the networks fill in through collective cell movements from the network edges. Our results indicate that network formation is mediated in part by substrate mechanics and that cellular traction force may promote cell-cell assembly by directing cell migration.
虽然已知影响血管生成和血管发生的生长因子和细胞因子已受到广泛关注，但关于机械环境如何影响血管形成和细胞组装的了解却较少。在本研究中，我们调查了底物弹性、内皮细胞-细胞连接性和牵引力产生之间的关系。我们发现，在更具顺应性的底物上，内皮细胞可独立于额外的外源性生长因子或细胞因子自组装成网络状结构。这些网络由亚汇合的内皮细胞在顺应性（E = 200 - 1000Pa）底物上组装而成，是内皮细胞增殖和迁移的结果。有趣的是，这些细胞-细胞连接和网络的稳定需要纤连蛋白聚合。牵引力显微镜测量表明，顺应性底物上的单个内皮细胞施加力，产生从细胞边缘传播的底物应变。我们推测这些应变将细胞拉到一起并启动自组装。值得注意的是，顺应性底物上的内皮细胞网络形成是动态和短暂的；随着细胞数量和底物应变增加，网络通过来自网络边缘的集体细胞运动而填充。我们的结果表明，网络形成部分由底物力学介导，并且细胞牵引力可能通过引导细胞迁移促进细胞-细胞组装。
