NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Piazza San Silvestro 12, Pisa 56127, Italy.
Biomaterials. 2013 Aug;34(25):6027-36. doi: 10.1016/j.biomaterials.2013.04.039. Epub 2013 May 18.
Cells are exposed to specific directional physical signals determined by the micro/nano-environment that in vivo coexist with some degree of topographical noise. Particularly in the nervous system, cell contact sensing of the extracellular environment plays a primary role in defining neurite initiation and final brain wiring. Here we study neuronal cell response to directional stimuli by exploiting nanogratings with controlled amount of random nanotopographical noise. The impact of noise on neurite guidance and focal adhesions (FAs) development is investigated in NGF-differentiating PC12 cells by confocal and TIRF microscopy. We show that the loss of neurite guidance is not linear with noise, but is a threshold effect, correlating with changes in FA maturation and spatial organization. Finally nocodazole, a drug that increases cell contractility, can improve neurite alignment by promoting aligned FA maturation. We argue that these results show new possibilities for successful implant strategies particularly in the context of nerve-regeneration devices.
细胞暴露于特定的定向物理信号，这些信号由微/纳环境决定，而微/纳环境在体内与一定程度的地形噪声共存。特别是在神经系统中，细胞对外界环境的接触感应在确定神经突的起始和最终大脑布线方面起着主要作用。在这里，我们通过利用具有受控量随机纳米地形噪声的纳米光栅来研究神经元细胞对定向刺激的反应。通过共聚焦和 TIRF 显微镜研究了噪声对 NGF 分化的 PC12 细胞中神经突引导和焦点粘连（FA）发育的影响。我们表明，神经突引导的丧失与噪声不成线性关系，而是一种阈值效应，与 FA 成熟和空间组织的变化相关。最后，细胞松弛素，一种增加细胞收缩性的药物，可以通过促进对齐的 FA 成熟来改善神经突对齐。我们认为，这些结果为成功的植入策略，特别是在神经再生装置的背景下，展示了新的可能性。
