Nanostructured substrates have been recognized to initiate transcriptional programs promoting cell proliferation. Specifically β-catenin has been identified as transcriptional regulator, activated by adhesion to nanostructures. We set out to identify processes responsible for nanostructure-induced endothelial β-catenin signaling. Transmission electron microscopy (TEM) of cell contacts to differently sized polyethylene terephthalate (PET) surface structures (ripples with 250 to 300 nm and walls with 1.5 µm periodicity) revealed different patterns of cell-substrate interactions. Cell adhesion to ripples occurred exclusively on ripple peaks, while cells were attached to walls continuously. The Src kinase inhibitor PP2 was active only in cells grown on ripples, while the Abl inhibitors dasatinib and imatinib suppressed β-catenin translocation on both structures. Moreover, Gd³⁺ sensitive Ca²⁺ entry was observed in response to mechanical stimulation or Ca²⁺ store depletion exclusively in cells grown on ripples. Both PP2 and Gd³⁺ suppressed β-catenin nuclear translocation along with proliferation in cells grown on ripples but not on walls. Our results suggest that adhesion of endothelial cells to ripple structured PET induces highly specific, interface topology-dependent changes in cellular signalling, characterized by promotion of Gd³⁺-sensitive Ca²⁺ entry and Src/Abl activation. We propose that these signaling events are crucially involved in nanostructure-induced promotion of cell proliferation.

中文翻译：

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增强的 Ca2+ 进入和酪氨酸磷酸化介导纳米结构诱导的内皮增殖。

纳米结构底物已被认为可以启动促进细胞增殖的转录程序。具体而言， β-连环蛋白已被鉴定为转录调节剂，通过粘附到纳米结构上而被激活。我们着手确定负责纳​​米结构诱导的内皮β-连环蛋白信号传导的过程。细胞与不同尺寸的聚对苯二甲酸乙二醇酯 (PET) 表面结构（250 至 300 nm 的波纹和 1.5  µ的壁）接触的透射电子显微镜 (TEM)m 周期性）揭示了细胞 - 底物相互作用的不同模式。细胞对波纹的粘附仅发生在波纹峰上，而细胞则连续附着在墙上。Src 激酶抑制剂 PP2 仅在波纹上生长的细胞中具有活性，而 Abl 抑制剂达沙替尼和伊马替尼抑制两种结构上的β-连环蛋白易位。此外，观察到 Gd ³⁺敏感 Ca ²⁺进入响应于机械刺激或仅在波纹上生长的细胞中的Ca ^{2+储存耗尽。}PP2 和 Gd ³⁺均抑制β-连环蛋白核易位以及在波纹上而不是在墙上生长的细胞中的增殖。我们的结果表明，内皮细胞与波纹结构 PET 的粘附诱导细胞信号传导的高度特异性、界面拓扑依赖性变化，其特征在于促进 Gd ³⁺敏感的Ca ²⁺进入和 Src/Abl 激活。我们提出这些信号事件与纳米结构诱导的细胞增殖促进密切相关。