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首页> 外文期刊>Science Advances >Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation
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Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation

机译:NanoScale Integrin Cluster Dynamics通过FAKY397磷酸化控制蜂窝机械损伤

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摘要

Transduction of extracellular matrix mechanics affects cell migration, proliferation, and differentiation. While this mechanotransduction is known to depend on the regulation of focal adhesion kinase phosphorylation on Y397 (FAKpY397), the mechanism remains elusive. To address this, we developed a mathematical model to test the hypothesis that FAKpY397-based mechanosensing arises from the dynamics of nanoscale integrin clustering, stiffness-dependent disassembly of integrin clusters, and FAKY397 phosphorylation within integrin clusters. Modeling results predicted that integrin clustering dynamics governs how cells convert substrate stiffness to FAKpY397, and hence governs how different cell types transduce mechanical signals. Existing experiments on MDCK cells and HT1080 cells, as well as our new experiments on 3T3 fibroblasts, confirmed our predictions and supported our model. Our results suggest a new pathway by which integrin clusters enable cells to calibrate responses to their mechanical microenvironment.
机译:细胞外基质力学的转导影响细胞迁移,增殖和分化。虽然已知该机械手术取决于Y397(FAKPY397)对局灶性粘附激酶磷酸化的调节,但该机制仍然难以捉摸。为了解决这一点,我们开发了一种数学模型来测试Fakpy397的机械损伤,从纳米级整合蛋白聚类,整合簇的刚度依赖性拆卸的动态产生的假设,以及整合蛋白集群内的Faky397磷酸化。建模结果预测,整合素聚类动力学管理细胞如何将基板刚度转换为FAKPY397,因此控制不同的细胞类型如何转换机械信号。现有关于MDCK细胞和HT1080细胞的实验,以及我们对3T3成纤维细胞的新实验,证实了我们的预测并支持我们的模型。我们的结果表明,整合素集群使细胞能够校准对其机械微环境的响应的新途径。

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