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首页> 美国卫生研究院文献>Scientific Reports >Ring-Shaped Microlanes and Chemical Barriers as a Platform for Probing Single-Cell Migration
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Ring-Shaped Microlanes and Chemical Barriers as a Platform for Probing Single-Cell Migration

机译：环形微通道和化学屏障作为探测单细胞迁移的平台

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摘要

Quantification and discrimination of pharmaceutical and disease-related effects on cell migration requires detailed characterization of single-cell motility. In this context, micropatterned substrates that constrain cells within defined geometries facilitate quantitative readout of locomotion. Here, we study quasi-one-dimensional cell migration in ring-shaped microlanes. We observe bimodal behavior in form of alternating states of directional migration (run state) and reorientation (rest state). Both states show exponential lifetime distributions with characteristic persistence times, which, together with the cell velocity in the run state, provide a set of parameters that succinctly describe cell motion. By introducing PEGylated barriers of different widths into the lane, we extend this description by quantifying the effects of abrupt changes in substrate chemistry on migrating cells. The transit probability decreases exponentially as a function of barrier width, thus specifying a characteristic penetration depth of the leading lamellipodia. Applying this fingerprint-like characterization of cell motion, we compare different cell lines, and demonstrate that the cancer drug candidate salinomycin affects transit probability and resting time, but not run time or run velocity. Hence, the presented assay allows to assess multiple migration-related parameters, permits detailed characterization of cell motility, and has potential applications in cell biology and advanced drug screening.
机译：药物和疾病相关影响对细胞迁移的量化和区分需要对单细胞运动性进行详细表征。在这种情况下，将图案限制在定义的几何形状内的单元的微图案化底物有助于定量读取运动。在这里，我们研究环形微通道中的准一维细胞迁移。我们观察到双峰行为以方向迁移（运行状态）和重新定向（静止状态）的交替状态的形式出现。两种状态均显示具有特征性持久时间的指数寿命分布，其与运行状态下的细胞速度一起提供了一组简洁地描述细胞运动的参数。通过将不同宽度的聚乙二醇化屏障引入泳道，我们通过量化底物化学突变对迁移细胞的影响来扩展此描述。传递概率根据势垒宽度呈指数下降，从而确定了前板状脂溢性菌的特征性穿透深度。应用细胞运动的这种类似指纹的特征，我们比较了不同的细胞系，并证明了癌症候选药物沙利霉素会影响转运概率和静止时间，但不会影响运行时间或运行速度。因此，提出的测定法允许评估多个与迁移相关的参数，允许对细胞运动性进行详细表征，并且在细胞生物学和高级药物筛选中具有潜在的应用。

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