Subcellular control Rac-GTPase signalling by magnetogenetic manipulation inside living cells
Subcellular control Rac-GTPase signalling by magnetogenetic manipulation inside living cells
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DOI：
10.1038/nnano.2013.23
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发表时间：
2013-03-01
影响因子：
38.3
通讯作者：
Dahan, M.
中科院分区：
文献类型：
--
作者：
Etoc, F.;Lisse, D.;Dahan, M.
许多细胞功能依赖于亚细胞尺度上信号传导途径的协调活动（1，2）。然而，很少有工具能够探测和干扰信号网络的空间分辨率匹配其活动模式的细胞内尺寸。在这里，我们提出了一个通用的磁遗传方法的基础上的自组装的信号复合物的表面上的功能化的磁性纳米粒子活细胞内。纳米颗粒作为纳米级热点，可以通过磁力移动并触发信号转导途径，从而引起细胞反应。我们将这种策略应用于Rho-GTP酶，Rho-GTP酶是一组已知通过复杂的时空活性模式调节细胞形态的分子开关（3，4）。我们证明，纳米粒子介导的信号通路的激活导致局部的肌动蛋白细胞骨架的重塑和形态学的变化。
Many cell functions rely on the coordinated activity of signalling pathways at a subcellular scale(1,2). However, there are few tools capable of probing and perturbing signalling networks with a spatial resolution matching the intracellular dimensions of their activity patterns. Here we present a generic magnetogenetic approach based on the self-assembly of signalling complexes on the surface of functionalized magnetic nanoparticles inside living cells. The nanoparticles act as nanoscopic hot spots that can be displaced by magnetic forces and trigger signal transduction pathways that bring about a cell response. We applied this strategy to Rho-GTPases, a set of molecular switches known to regulate cell morphology via complex spatiotemporal patterns of activity(3,4). We demonstrate that the nanoparticle-mediated activation of signalling pathways leads to local remodelling of the actin cytoskeleton and to morphological changes.