Nanomechanics controls neuronal precursors adhesion and differentiation
Nanomechanics controls neuronal precursors adhesion and differentiation
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DOI：
10.1002/bit.24880
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发表时间：
2013-08-01
影响因子：
3.8
通讯作者：
Lazzarino, Marco
中科院分区：
文献类型：
--
作者：
Migliorini, Elisa;Ban, Jelena;Lazzarino, Marco
控制干细胞分化为特定神经元类型的能力对于治疗神经退行性疾病具有巨大的潜力。体外神经元分化可以通过生物化学和生物物理学线索的相互作用来指导。已经提出了不同的策略，以提高分化产量，重点放在基板的地形，或者，可替代地对基板的刚度的一切。这两种策略都证明了细胞反应的改善。然而，往往是不可能分开的地形和机械的贡献。在这里，我们调查的纳米结构基板的机械性能的作用，旨在了解的最终参数，支配干细胞分化。为此目的，将一组具有受控刚度且具有或不具有纳米图案化的不同基底用于干细胞分化。我们的研究结果表明，神经元的分化产量主要取决于基板的机械性能，而几何形状起着次要的作用。特别是具有可比刚度的纳米结构和平坦的聚二甲基硅氧烷（PDMS）基底显示出相同的神经元产率。通过在亚微米尺度上的表面纳米图案化获得的分化产率的改善可以解释为基板软化效应的结果。最后，我们调查单细胞力谱的神经元前体粘附在基板上后立即播种，作为一个可能的关键步骤，管理神经元分化效率。我们观察到，神经元前体的粘附取决于基板的刚度，但不是表面结构，特别是它是更高的软基板。我们的研究结果表明，细胞-基质粘附力和机械响应是神经元再生医学中基质设计要考虑的关键参数。Biotechnol. Bioeng. 2013; 110：2301-2310. (c)2013 Wiley Periodicals，Inc.
The ability to control the differentiation of stem cells into specific neuronal types has a tremendous potential for the treatment of neurodegenerative diseases. In vitro neuronal differentiation can be guided by the interplay of biochemical and biophysical cues. Different strategies to increase the differentiation yield have been proposed, focusing everything on substrate topography, or, alternatively on substrate stiffness. Both strategies demonstrated an improvement of the cellular response. However it was often impossible to separate the topographical and the mechanical contributions. Here we investigate the role of the mechanical properties of nanostructured substrates, aiming at understanding the ultimate parameters which govern the stem cell differentiation. To this purpose a set of different substrates with controlled stiffness and with or without nanopatterning are used for stem cell differentiation. Our results show that the neuronal differentiation yield depends mainly on the substrate mechanical properties while the geometry plays a minor role. In particular nanostructured and flat polydimethylsiloxane (PDMS) substrates with comparable stiffness show the same neuronal yield. The improvement in the differentiation yield obtained through surface nanopatterning in the submicrometer scale could be explained as a consequence of a substrate softening effect. Finally we investigate by single cell force spectroscopy the neuronal precursor adhesion on the substrate immediately after seeding, as a possible critical step governing the neuronal differentiation efficiency. We observed that neuronal precursor adhesion depends on substrate stiffness but not on surface structure, and in particular it is higher on softer substrates. Our results suggest that cell-substrate adhesion forces and mechanical response are the key parameters to be considered for substrate design in neuronal regenerative medicine. Biotechnol. Bioeng. 2013; 110: 2301-2310. (c) 2013 Wiley Periodicals, Inc.