Actin and microtubule networks contribute differently to cell response for small and large strains
Actin and microtubule networks contribute differently to cell response for small and large strains
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DOI：
10.1088/1367-2630/aa7658
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发表时间：
2017-09-08
影响因子：
3.3
通讯作者：
Kaes, J.
中科院分区：
文献类型：
--
作者：
Kubitschke, H.;Schnauss, J.;Kaes, J.
细胞骨架丝为细胞提供机械稳定性和组织性。主要的关键参与者是肌动蛋白丝和微管，它们控制着细胞对机械刺激的反应。我们通过使MCF-7上皮细胞在小变形（5%变形）下变形来研究这些关键组分的具体影响。为了了解肌动蛋白丝和微管的具体贡献，我们系统地研究了细胞骨架影响药物治疗后的细胞反应。利用微流体光学拉伸器进行定量，可以捕获不同条件下细胞的相对变形和松弛。我们分离出两个数量级的药物剂量的肌动蛋白和微管网络的细胞力学独特的变形和松弛的贡献。例如，通过latrunculin A破坏肌动蛋白丝，揭示了一种不依赖于应变的软化。稳定这些细丝的处理jasplakinoline产生细胞软化的小菌株，但在大菌株没有显着变化。相反，用诺考达唑处理以破坏微管的细胞在大应变下显示软化，但在小应变下保持不变。通过紫杉醇稳定细胞内的微管显示在小应变下变形没有显著变化，但在大应变下具有浓度依赖性影响。这表明，对于悬浮细胞，肌动蛋白皮质是探测在小菌株，而在较大的菌株，整个细胞是探测与微管的显着贡献。
Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell's response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.