Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA.
Biophys J. 2010 Jan 6;98(1):67-75. doi: 10.1016/j.bpj.2009.09.051.
It has long been appreciated that spatiotemporal dynamics of cell migration are under the control of intracellular signaling pathways, which are mediated by adhesion receptors and other transducers of extracellular cues. Further, there is ample evidence that aspects of cell migration are stochastic: how else could it exhibit directional persistence over timescales much longer than typical signal transduction processes, punctuated by abrupt changes in direction? Yet the mechanisms by which signaling processes affect those behaviors remain unclear. We have developed analytical methods for relating parallel live-cell microscopy measurements of cell migration dynamics to the intracellular signaling processes that govern them. In this analysis of phosphoinositide 3-kinase signaling in randomly migrating fibroblasts, we observe that hot spots of intense signaling coincide with localized cell protrusion and endure with characteristic lifetimes that correspond to those of cell migration persistence. We further show that distant hot spots are dynamically and stochastically coupled. These results are indicative of a mechanism by which changes in a cell's direction of migration are determined by a fragile balance of relatively rapid intracellular signaling processes.
长期以来，人们一直认为细胞迁移的时空动力学受细胞内信号通路的控制，这些信号通路由黏附受体和其他细胞外信号转导体介导。此外，有充分的证据表明细胞迁移的某些方面是随机的：否则，它如何在比典型信号转导过程长得多的时间尺度上表现出定向持续性，而这些过程又会突然改变方向？然而，信号转导过程影响这些行为的机制尚不清楚。我们已经开发了将细胞迁移动力学的平行活细胞显微镜测量与控制它们的细胞内信号转导过程相关联的分析方法。在对随机迁移成纤维细胞中的磷酸肌醇 3-激酶信号的分析中，我们观察到强烈信号的热点与局部细胞突出相一致，并具有与细胞迁移持续性相对应的特征寿命。我们进一步表明，遥远的热点是动态和随机耦合的。这些结果表明，细胞迁移方向的变化是由相对快速的细胞内信号转导过程的脆弱平衡决定的。
