Actin filaments play a primary role for structural integrity and viscoelastic response in cells
Actin filaments play a primary role for structural integrity and viscoelastic response in cells
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DOI：
10.1039/c2ib00168c
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发表时间：
2012-01-01
影响因子：
2.5
通讯作者：
Agah, Masoud
中科院分区：
文献类型：
--
作者：
Ketene, Alperen N.;Roberts, Paul C.;Agah, Masoud
这项原子力显微镜 (AFM) 研究致力于分析小鼠卵巢癌细胞的细胞骨架成分以及肌动蛋白和微管蛋白丝对细胞变形行为的影响。早期的非致瘤性癌细胞表现出丰富的、组织良好的细胞骨架结构，由肌动蛋白和微管丝组成。与此形成鲜明对比的是，代表癌症晚期和更具侵袭性阶段的细胞表现出高度混乱的肌动蛋白和微管结构。通过使用肌动蛋白微丝靶向药物，以及辛二酰苯胺异羟肟酸 (SAHA) 和图巴他汀 A 抗癌药物，我们修改了细胞结构框架并进行了纳米压痕测试，以评估细胞弹性和粘度作为每种生物聚合物加权存在的函数。结果表明，这两种机械性能都受到肌动蛋白微丝水平和组织状态的严重影响；减少细胞的肌动蛋白组织会导致细胞弹性和粘度分别降低 85% 和 79%。相比之下，微管组织仅对任一特性产生边际效应。此外，抗癌药物 SAHA 对癌细胞的粘弹性反应几乎没有影响。最后，我们首次报告，AFM 测试显示，一种特定的 HDAC6 抑制剂 Tustatatin A 可以增加细胞弹性，而不会对肌动蛋白微丝或微管网络产生剧烈变化。我们的研究结果引起了人们对潜在 HDAC6 靶点的兴趣，该靶点与传统已知的细胞骨架成分一样有效地影响细胞力学。
This atomic force microscopy (AFM) study is devoted to the analysis of the mouse ovarian cancer cell's cytoskeleton components and the impact of both actin and microtubulin filaments on a cell's deformation behavior. Early stage, non-tumorigenic cancer cells show abundant well-organized cytoskeletal structures consisting of both actin and microtubule filaments. In sharp contrast, cells representing late and more aggressive stages of cancer display highly disorganized actin and microtubule structures. With the use of actin microfilament targeting drugs, together with the suberoylanilide hydroxamic acid (SAHA) and tubastatin A anti-cancer drugs, we modified the cell architectural framework and performed nano-indentation tests to evaluate cell elasticity and viscosity as a function of each biopolymer's weighted presence. Results demonstrate that both mechanical properties are heavily influenced by the levels and organization state of actin microfilaments; decreasing the actin organization of cells results in 85% and 79% decrease in cell elasticity and viscosity, respectively. In contrast, microtubule organization was shown to exert only marginal effects on either property. Furthermore, the anti-cancer drug, SAHA, was shown to exert little impact on the viscoelastic response of cancer cells. Finally, we report for the first time that tubastatin A, a specific HDAC6 inhibitor, increased cell elasticity as revealed by AFM tests without exerting drastic changes to the actin microfilament or microtubule networks. Our findings raise interest in a potential HDAC6 target that affects cellular mechanics just as effectively as the conventionally known cytoskeleton components.