Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.
Cytoskeleton (Hoboken). 2010 Apr;67(4):224-40. doi: 10.1002/cm.20438.
Cell motility contributes to the formation of organs and tissues, into which multiple cells self-organize. However such mammalian cellular motilities are not characterized in a quantitative manner and the systemic consequences are thus unknown. A mathematical tool to decipher cell motility, accounting for changes in cell shape, within a three-dimensional (3D) cell system was missing. We report here such a tool, usable on segmented images reporting the outline of clusters (cells) and allowing the time-resolved 3D analysis of circular motility of these as parts of a system (cell aggregate). Our method can analyze circular motility in sub-cellular, cellular, multi-cellular, and also non-cellular systems for which time-resolved segmented cluster outlines are available. To exemplify, we characterized the circular motility of lumen-initiating MDCK cell aggregates, embedded in extracellular matrix. We show that the organization of the major surrounding matrix fibers was not significantly affected during this cohort rotation. Using our developed tool, we discovered two classes of circular motion, rotation and random walk, organized in three behavior patterns during lumen initiation. As rotational movements were more rapid than random walk and as both could continue during lumen initiation, we conclude that neither the class nor the rate of motion regulates lumen initiation. We thus reveal a high degree of plasticity during a developmentally critical cell polarization step, indicating that lumen initiation is a robust process. However, motility rates decreased with increasing cell number, previously shown to correlate with epithelial polarization, suggesting that migratory polarization is converted into epithelial polarization during aggregate development.
细胞运动有助于器官和组织的形成，在这些器官和组织中，多个细胞会自我组织。然而，哺乳动物细胞的这种运动方式并没有以定量的方式来描述，因此其系统后果尚不清楚。缺乏一种能够解释细胞运动的数学工具，这种工具需要考虑细胞形状的变化，并且适用于三维（3D）细胞系统。我们在这里报告了这样一种工具，它可以用于报告细胞簇（细胞）轮廓的分割图像，并允许对这些作为系统一部分（细胞聚集体）的圆形运动进行时间分辨的 3D 分析。我们的方法可以分析亚细胞、细胞、多细胞以及具有可用时间分辨分割簇轮廓的非细胞系统中的圆形运动。例如，我们描述了在细胞外基质中嵌入的腔起始 MDCK 细胞聚集体的圆形运动。我们发现，在这个细胞群体旋转过程中，主要的周围基质纤维的组织并没有受到显著影响。使用我们开发的工具，我们发现了两种圆形运动，旋转和随机漫步，并在腔起始过程中组织成三种行为模式。由于旋转运动比随机漫步更快，并且两者都可以在腔起始过程中继续，因此我们得出结论，无论是运动的类型还是速度都不会调节腔的起始。因此，我们揭示了在一个发育关键的细胞极化步骤中具有高度的可塑性，表明腔的起始是一个稳健的过程。然而，随着细胞数量的增加，运动速度会降低，这与上皮极化有关，这表明迁移极化在聚集体发育过程中转化为上皮极化。
