Biological tissues contain micrometer-scale gaps and pores, including those found within extracellular matrix fiber networks, between tightly packed cells, and between blood vessels or nerve bundles and their associated basement membranes. These spaces restrict cell motion to a single-spatial dimension (1D), a feature that is not captured in traditional in vitro cell migration assays performed on flat, unconfined two-dimensional (2D) substrates. Mechanical confinement can variably influence cell migration behaviors, and it is presently unclear whether the mechanisms used for migration in 2D unconfined environments are relevant in 1D confined environments. Here, we assessed whether a cell migration simulator and associated parameters previously measured for cells on 2D unconfined compliant hydrogels could predict 1D confined cell migration in microfluidic channels. We manufactured microfluidic devices with narrow channels (60-μm2 rectangular cross-sectional area) and tracked human glioma cells that spontaneously migrated within channels. Cell velocities (vexp = 0.51 ± 0.02 μm min−1) were comparable to brain tumor expansion rates measured in the clinic. Using motor-clutch model parameters estimated from cells on unconfined 2D planar hydrogel substrates, simulations predicted similar migration velocities (vsim = 0.37 ± 0.04 μm min−1) and also predicted the effects of drugs targeting the motor-clutch system or cytoskeletal assembly. These results are consistent with glioma cells utilizing a motor-clutch system to migrate in confined environments.

中文翻译：

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根据校准到 2D 电机离合器模型的参数预测受限 1D 细胞迁移


生物组织含有微米级的间隙和孔，包括细胞外基质纤维网络内、紧密堆积的细胞之间以及血管或神经束及其相关基底膜之间的间隙和孔。这些空间将细胞运动限制在单一空间维度 (1D)，这是在平坦、无限制的二维 (2D) 基质上进行的传统体外细胞迁移测定中无法捕获的特征。机械限制可以不同程度地影响细胞迁移行为，目前尚不清楚二维无限制环境中用于迁移的机制是否与一维限制环境相关。在这里，我们评估了细胞迁移模拟器和先前在 2D 无约束顺应性水凝胶上测量的细胞的相关参数是否可以预测微流体通道中的 1D 约束细胞迁移。我们制造了具有狭窄通道（60μm2矩形横截面积）的微流体装置，并跟踪在通道内自发迁移的人类神经胶质瘤细胞。细胞速度（vexp = 0.51 ± 0.02 μm min−1）与临床测量的脑肿瘤扩张率相当。使用从无侧限 2D 平面水凝胶基底上的细胞估计的电机离合器模型参数，模拟预测了类似的迁移速度 (vsim = 0.37 ± 0.04 μm min−1)，并预测了针对电机离合器系统或细胞骨架组件的药物的效果。这些结果与神经胶质瘤细胞利用电机离合器系统在受限环境中迁移一致。