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Nature Materials:小机械力或对胚胎干细胞产生大影响

来源:生命经纬 2009-10-21 10:58

伊利诺伊大学的研究人员发现,给胚胎干细胞(ESCs)施加一个微小的机械力,能引起胚胎干细胞强烈的生物学反应,并引导其向特殊的方向分化。该研究或许能应用到开发治疗性的克隆和再生的药物上。这篇研究报告发表在Nature Materials杂志上。

细胞柔软性(Cell softness)是胚胎干细胞的内在特性,控制着细胞生理环境中对各种力的反应。为了研究细胞对力的敏感性,课题组将直径4微米的磁珠置于活的胚胎干细胞表面,然后施加一个微小的震荡磁场,使磁珠在磁场中来回震荡。通过精确测量磁场以及磁珠震荡的距离,可以计算出对细胞施加的机械力以及细胞的柔软性。

据研究人员介绍,机械力的周期性非常重要,它能够刺激细胞内部的力的产生,如肌球蛋白周期性运动。研究人员发现老鼠的胚胎干细胞相比其分化为其他类型的细胞要更柔软,对局部周期性的力更敏感。

此外,研究人员利用这种周期性的力对人类的肌肉细胞进行研究,得到同样的试验结果。为了研究这种局部的机械力对老鼠胚胎干细胞分化的长期影响,研究人员将绿色荧光蛋白基因导入到胚胎干细胞进行表达,再将其置于机械力作用下,发现在磁珠作用下,细胞内的绿色荧光逐渐消退,这说明基因表达量降低。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature Materials 18 October 2009 | doi:10.1038/nmat2563

Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells

Farhan Chowdhury1, Sungsoo Na1,2,5, Dong Li3,5, Yeh-Chuin Poh1, Tetsuya S. Tanaka4, Fei Wang3 & Ning Wang1

Growing evidence suggests that physical microenvironments and mechanical stresses, in addition to soluble factors, help direct mesenchymal-stem-cell fate. However, biological responses to a local force in embryonic stem cells remain elusive. Here we show that a local cyclic stress through focal adhesions induced spreading in mouse embryonic stem cells but not in mouse embryonic stem-cell-differentiated cells, which were ten times stiffer. This response was dictated by the cell material property (cell softness), suggesting that a threshold cell deformation is the key setpoint for triggering spreading responses. Traction quantification and pharmacological or shRNA intervention revealed that myosin II contractility, F-actin, Src or cdc42 were essential in the spreading response. The applied stress led to oct3/4 gene downregulation in mES cells. Our findings demonstrate that cell softness dictates cellular sensitivity to force, suggesting that local small forces might have far more important roles in early development of soft embryos than previously appreciated.

1 Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Illinois 61801, USA
2 Indiana University-Purdue University Indianapolis, Department of Biomedical Engineering, 723 W. Michigan St. SL220, Indianapolis, Indiana 46202, USA
3 Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Illinois 61801, USA
4 Department of Animal Sciences, University of Illinois at Urbana-Champaign, Illinois 61801, USA
5 These authors contributed equally to this work

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