Maeda Yusuke T, Inose Junya, Matsuo Miki Y, Iwaya Suguru, Sano Masaki
Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
PLoS One. 2008;3(11):e3734. doi: 10.1371/journal.pone.0003734. Epub 2008 Nov 17.
In the absence of stimuli, most motile eukaryotic cells move by spontaneously coordinating cell deformation with cell movement in the absence of stimuli. Yet little is known about how cells change their own shape and how cells coordinate the deformation and movement. Here, we investigated the mechanism of spontaneous cell migration by using computational analyses.
We observed spontaneously migrating Dictyostelium cells in both a vegetative state (round cell shape and slow motion) and starved one (elongated cell shape and fast motion). We then extracted regular patterns of morphological dynamics and the pattern-dependent systematic coordination with filamentous actin (F-actin) and cell movement by statistical dynamic analyses.
CONCLUSIONS/SIGNIFICANCE: We found that Dictyostelium cells in both vegetative and starved states commonly organize their own shape into three ordered patterns, elongation, rotation, and oscillation, in the absence of external stimuli. Further, cells inactivated for PI3-kinase (PI3K) and/or PTEN did not show ordered patterns due to the lack of spatial control in pseudopodial formation in both the vegetative and starved states. We also found that spontaneous polarization was achieved in starved cells by asymmetric localization of PTEN and F-actin. This breaking of the symmetry of protein localization maintained the leading edge and considerably enhanced the persistence of directed migration, and overall random exploration was ensured by switching among the different ordered patterns. Our findings suggest that Dictyostelium cells spontaneously create the ordered patterns of cell shape mediated by PI3K/PTEN/F-actin and control the direction of cell movement by coordination with these patterns even in the absence of external stimuli.
在没有刺激的情况下,大多数能动的真核细胞通过在无刺激时自发地协调细胞变形与细胞运动来移动。然而,关于细胞如何改变自身形状以及如何协调变形和运动,我们所知甚少。在此,我们通过计算分析研究了自发细胞迁移的机制。
我们观察了处于营养状态(圆形细胞形状且运动缓慢)和饥饿状态(细长细胞形状且运动快速)下自发迁移的盘基网柄菌细胞。然后,我们通过统计动力学分析提取了形态动力学的规则模式以及与丝状肌动蛋白(F-肌动蛋白)和细胞运动相关的模式依赖性系统协调。
结论/意义:我们发现,处于营养和饥饿状态的盘基网柄菌细胞在没有外部刺激的情况下通常将自身形状组织成三种有序模式,即伸长、旋转和振荡。此外,由于在营养和饥饿状态下伪足形成缺乏空间控制,PI3激酶(PI3K)和/或PTEN失活的细胞未显示出有序模式。我们还发现,饥饿细胞通过PTEN和F-肌动蛋白的不对称定位实现了自发极化。这种蛋白质定位对称性的打破维持了前沿并显著增强了定向迁移的持续性,并且通过在不同有序模式之间切换确保了整体随机探索。我们的研究结果表明,即使在没有外部刺激的情况下,盘基网柄菌细胞也能自发地创建由PI3K/PTEN/F-肌动蛋白介导的细胞形状有序模式,并通过与这些模式的协调来控制细胞运动方向。