Mechanical interactions among cytoskeletal filaments

Mechanical interactions among cytoskeletal filaments
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DOI:
10.1161/01.hyp.32.1.162
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发表时间:
1998-07-01
期刊:
影响因子:
8.3
通讯作者:
Wang, N
Wang, N
中科院分区:
医学1区
文献类型:
--
作者:
Wang, N

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细胞的机械性能在控制细胞形状、细胞迁移和其他功能方面很重要。为了了解细胞骨架(CSK)细丝之间的机械相互作用,分析了细胞骨架(CSK)干扰药物处理后贴壁内皮细胞的力学特性。用磁扭转细胞仪测量CSK硬度(应力应变之比,衡量细胞对形状变形的抵抗力)、粘滞指数(细胞内结构阻尼指数)和永久变形(衡量“可塑性”的指标),通过旋转应力直接将旋转应力施加到包覆含RGD多肽的铁磁珠上。细胞松弛素D可以破坏肌动蛋白微丝,使肌动蛋白微丝的硬度降低50%,永久变形量从70%减少到50%,但对粘度几乎没有影响。相比之下,微管阻断剂诺康唑对CSK僵硬的抑制作用很小,粘度降低了25%,对永久变形没有影响。中间纤维阻断剂丙烯酰胺对CSK硬度的抑制作用不大,对粘度影响不大,对永久变形影响不大。紫杉醇,一种促进微管聚合的药物,增加了10%的硬度,增加了10%的粘度,并将永久变形从70%减少到50%。细胞松弛素D和诺可达唑、细胞松弛素D和丙烯酰胺或三种药物联合使用对抑制CSK僵硬和黏度有协同作用,但对永久性变形无明显影响。氰化钾抑制氧化代谢对应激诱导的僵直反应没有影响。用氧化苯砷抑制酪氨酸磷酸酶对应激诱导的僵直反应没有影响。我们得出结论,CSK细丝的高阶机械相互作用在决定细胞的力学性质方面是重要的。
Mechanical properties of the cells are important in controlling cell shape, cell migration, and other functions. To understand how cytoskeletal (CSK) filaments interact with one another mechanically, mechanical properties of adherent endothelial cells were analyzed after treatment with CSK-disrupting drugs. CSK stiffness (the ratio of applied stress to strain, a measure of cell resistance to shape deformation), viscosity tan index of intracellular structural damping), and permanent deformation (a measure of "plasticity") were measured with magnetic twisting cytometry, by which rotational stress was applied directly to integrin receptors with ferromagnetic beads coated with RGD-containing peptide. Treatment with cytochalasin D, which disrupts actin microfilaments inhibited stiffness by 50% and decreased permanent deformation from 70% to 50% but had almost no effect on viscosity. In contrast, nocodazole, a microtubule disrupter, had very little effect on inhibition of CSK stiffness, decreased viscosity by 25%, and had no effects on permanent deformation. Acrylamide, an intermediate filament disrupter, had little effect on inhibition of CSK stiffness, little effect on viscosity, and no effect on permanent deformation. Taxol, a drug that facilitates microtubule polymerization, increased stiffness by 10%, increased viscosity by 10%, and decreased permanent deformation from 70% to 50%. Combinations of cytochalasin D and nocodazole, cytochalasin D and acrylamide, or all three drugs resulted in a synergistic effect on inhibition of CSK stiffness and viscosity but not in permanent deformation. Inhibition of oxidative metabolism with potassium cyanide had no effects on stress-induced stiffening response. Inhibition of tyrosine phosphatase with phenylarsine oxide had no effect on stress-induced stiffening response. We conclude that higher order mechanical interactions of CSK filaments are important in determining the mechanical properties of the cell.