The effect of Young's modulus on the neuronal differentiation of mouse embryonic stem cells
The effect of Young's modulus on the neuronal differentiation of mouse embryonic stem cells
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DOI：
10.1016/j.actbio.2015.07.008
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发表时间：
2015-10-01
影响因子：
9.7
通讯作者：
Veraitch, Farlan S.
中科院分区：
文献类型：
--
作者：
Ali, Shahzad;Wall, Ivan B.;Veraitch, Farlan S.
有大量证据表明，细胞对ECM硬度的变化产生不同的反应，这取决于它们的身份。我们的目的是了解硬度如何影响胚胎干细胞（ESC）的神经元分化，以及这在分化过程的三个特定阶段是如何变化的。在本研究中，考虑了刚度对细胞的三种影响；分化过程中的附着、扩张和表型变化。刚度从2kpa到18kpa，最后达到35kpa。研究发现，ESC（与2 kPa相比，35 kPa时减少95%）和神经前体（35 kPa时减少83%）的附着都随着刚度的增加而减少。未成熟神经元的附着不受僵硬的影响。在所有细胞类型中，细胞的膨胀与细胞的刚度无关，这意味着细胞在分化过程中的增殖与杨氏模量无关。在mESC和神经前体分化过程中，硬度对表型变化没有影响。2 kPa增加了未成熟神经元向成熟神经元分化的细胞比例。综上所述，我们的研究结果表明，随着神经元细胞变得更加成熟，杨氏模量对附着的影响会减弱。相反，杨氏模量对表型变化的影响随着细胞变得更成熟而增加。(C) 2015材料学报Elsevier Ltd.出版。
There is substantial evidence that cells produce a diverse response to changes in ECM stiffness depending on their identity. Our aim was to understand how stiffness impacts neuronal differentiation of embryonic stem cells (ESC's), and how this varies at three specific stages of the differentiation process. In this investigation, three effects of stiffness on cells were considered; attachment, expansion and phenotypic changes during differentiation. Stiffness was varied from 2 kPa to 18 kPa to finally 35 kPa. Attachment was found to decrease with increasing stiffness for both ESC's (with a 95% decrease on 35 kPa compared to 2 kPa) and neural precursors (with a 83% decrease on 35 kPa). The attachment of immature neurons was unaffected by stiffness. Expansion was independent of stiffness for all cell types, implying that the proliferation of cells during this differentiation process was independent of Young's modulus. Stiffness had no effect upon phenotypic changes during differentiation for mESC's and neural precursors. 2 kPa increased the proportion of cells that differentiated from immature into mature neurons. Taken together our findings imply that the impact of Young's modulus on attachment diminishes as neuronal cells become more mature. Conversely, the impact of Young's modulus on changes in phenotype increased as cells became more mature. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd.