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首页> 美国卫生研究院文献>ACS AuthorChoice >Nanomechanical Property Maps of Breast Cancer CellsAs Determined by Multiharmonic Atomic Force Microscopy Reveal Syk-DependentChanges in MicrotubuleStability Mediated by MAP1B
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Nanomechanical Property Maps of Breast Cancer CellsAs Determined by Multiharmonic Atomic Force Microscopy Reveal Syk-DependentChanges in MicrotubuleStability Mediated by MAP1B

机译：乳腺癌细胞的纳米力学特性图由多谐波原子力显微镜确定揭示Syk依赖微管的变化MAP1B介导的稳定性

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摘要

The Syk protein-tyrosine kinase, a well-characterized modulator of immune recognition receptor signaling, also plays important, but poorly characterized, roles in tumor progression, acting as an inhibitor of cellular motility and metastasis in highly invasive cancer cells. Multiharmonic atomic force microscopy (AFM) was used to map nanomechanical properties of live MDA-MB-231 breast cancer cells either lacking or expressing Syk. The expression of Syk dramatically altered the cellular topography, reduced cell height, increased elasticity, increased viscosity, and allowed visualization of a more substantial microtubule network. The microtubules of Syk-expressing cells were more stable to nocodazole-induced depolymerization and were more highly acetylated than those of Syk-deficient cells. Silencing of MAP1B, a major substrate for Syk in MDA-MB-231 cells, attenuated Syk-dependent microtubule stability and reversed much of the effect of Syk on cellular topography, stiffness, and viscosity. This study illustrates the use of multiharmonic AFM both to quantitativelymap the local nanomechanical propertiesof living cells and to identify the underlying mechanisms by whichthese properties are modulated by signal transduction machinery.
机译：Syk蛋白-酪氨酸激酶是免疫识别受体信号转导的良好表征调节剂，在肿瘤进展中也起着重要但尚未充分表征的作用，在高侵袭性癌细胞中起着细胞运动和转移的抑制剂的作用。多谐波原子力显微镜（AFM）用于绘制缺少或表达Syk的活MDA-MB-231乳腺癌细胞的纳米力学性能。 Syk的表达极大地改变了细胞的形貌，降低了细胞的高度，增加了弹性，增加了粘度，并使更显着的微管网络可视化。 Syk表达细胞的微管对Nocodazole诱导的解聚反应更稳定，并且乙酰化程度比Syk缺陷细胞更高。 MAP1B（MDA-MB-231细胞中Syk的主要底物）的沉默减弱了Syk依赖性微管的稳定性，并逆转了Syk对细胞形貌，硬度和粘度的许多影响。这项研究说明了使用多谐波AFM进行定量绘制局部纳米力学特性活细胞并确定其潜在机制这些特性通过信号转导机制进行调节。

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