Filamin A (FLNa) belongs to an actin-binding protein family in binding and cross-linking actin filaments into a three-dimensional structure. However, little attention has been given to its mechanobiological role in cancer cells. Here, we quantitatively investigated the role of FLNa by analyzing the following parameters in negative control (NC) and FLNa-knockdown (KD) U87 glioma cells using submicron pillars (900 nm diameter and 2 μm height): traction force (TF), rigidity sensing ability, cell aspect ratio, migration speed, and invasiveness. During the initial phase of cell adhesion (< 1 h), FLNa-KD cells polarized more slowly than did NC cells, which can be explained by the loss of rigidity sensing in FLNa-KD cells. The higher motility of FLNa-KD cells relative to NC cells can be explained by the high TF exerted by FLNa-KD cells when compared to NC cells, while the higher invasiveness of FLNa-KD cells relative to NC cells can be explained by a greater number of filopodia in FLNa-KD cells than in NC cells. Our results suggest that FLNa plays important roles in suppressing motility and invasiveness of U87 cells.

中文翻译：

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使用亚微米软柱探索细丝蛋白 A 在人 U87 胶质母细胞瘤细胞迁移和侵袭中的机械生物学作用

细丝蛋白 A (FLNa) 属于肌动蛋白结合蛋白家族，可将肌动蛋白丝结合并交联成三维结构。然而，很少有人注意到它在癌细胞中的机械生物学作用。在这里，我们通过使用亚微米柱（900 nm 直径和 2 μm 高度）分析阴性对照 (NC) 和 FLNa 击倒 (KD) U87 神经胶质瘤细胞中的以下参数来定量研究 FLNa 的作用：牵引力 (TF)、刚度感知能力、细胞纵横比、迁移速度和侵袭性。在细胞粘附的初始阶段（< 1 h），FLNa-KD 细胞极化比 NC 细胞更慢，这可以通过 FLNa-KD 细胞中刚性感应的丧失来解释。FLNa-KD 细胞相对于 NC 细胞具有更高的运动性可以通过与 NC 细胞相比 FLNa-KD 细胞产生的高 TF 来解释，而 FLNa-KD 细胞相对于 NC 细胞的更高侵袭性可以解释为更大的FLNa-KD 细胞中丝状伪足的数量多于 NC 细胞。我们的结果表明 FLNa 在抑制 U87 细胞的运动性和侵袭性方面起着重要作用。