Cell migration is highly sensitive to fluid shear stress (FSS) in blood flow or interstitial fluid flow. However, whether the FSS gradient can regulate the migration of cells remains unclear. In this work, we constructed a parallel-plate flow chamber with different FSS gradients and verified the gradient flow field by particle image velocimetry measurements and finite element analyses. We then investigated the effect of FSS magnitudes and gradients on the migration of osteoclast precursor RAW264.7 cells. Results showed that the cells sensed the FSS gradient and migrated toward the low-FSS region. This FSS gradient-induced migration tended to occur in low-FSS magnitudes and high gradients, e.g., the migration angle relative to flow direction was approximately 90° for 0.1 Pa FSS and 0.2 Pa mm-1 FSS gradient. When chemically inhibiting the calcium signaling pathways of the mechanosensitive cation channel, endoplasmic reticulum, phospholipase C, and extracellular calcium, the cell migration toward the low-FSS region was significantly reduced. This study may provide insights into the mechanism of the recruitment of osteoclast precursors at the site of bone resorption and of mechanical stimulation-induced bone remodeling.

中文翻译：

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梯度流体剪切应力调节破骨细胞前体的迁移。

细胞迁移对血流或间质液流中的流体切应力（FSS）高度敏感。但是，FSS梯度是否可以调节细胞迁移仍不清楚。在这项工作中，我们构造了具有不同FSS梯度的平行板流动室，并通过粒子图像测速测量和有限元分析验证了梯度流场。然后，我们研究了FSS幅度和梯度对破骨细胞前体RAW264.7细胞迁移的影响。结果表明细胞感知到FSS梯度并向低FSS区域迁移。由FSS梯度引起的迁移倾向于以低FSS幅度和高梯度发生，例如，对于0.1 Pa FSS和0.2 Pa mm-1 FSS梯度，相对于流向的迁移角约为90°。当化学抑制机械敏感阳离子通道，内质网，磷脂酶C和细胞外钙的钙信号传导途径时，细胞向低FSS区的迁移明显减少。这项研究可以提供破骨细胞前体在骨吸收部位募集的机制以及机械刺激引起的骨重塑的机制的见解。