伊利諾伊大學(xué)的研究人員發(fā)現(xiàn),,給胚胎干細胞(ESCs)施加一個微小的機械力,能引起胚胎干細胞強烈的生物學(xué)反應(yīng),,并引導(dǎo)其向特殊的方向分化,。該研究或許能應(yīng)用到開發(fā)治療性的克隆和再生的藥物上。這篇研究報告發(fā)表在Nature Materials雜志上,。
細胞柔軟性(Cell softness)是胚胎干細胞的內(nèi)在特性,,控制著細胞生理環(huán)境中對各種力的反應(yīng)。為了研究細胞對力的敏感性,,課題組將直徑4微米的磁珠置于活的胚胎干細胞表面,,然后施加一個微小的震蕩磁場,使磁珠在磁場中來回震蕩,。通過精確測量磁場以及磁珠震蕩的距離,,可以計算出對細胞施加的機械力以及細胞的柔軟性。
據(jù)研究人員介紹,機械力的周期性非常重要,,它能夠刺激細胞內(nèi)部的力的產(chǎn)生,,如肌球蛋白周期性運動。研究人員發(fā)現(xiàn)老鼠的胚胎干細胞相比其分化為其他類型的細胞要更柔軟,,對局部周期性的力更敏感,。
此外,研究人員利用這種周期性的力對人類的肌肉細胞進行研究,,得到同樣的試驗結(jié)果,。為了研究這種局部的機械力對老鼠胚胎干細胞分化的長期影響,研究人員將綠色熒光蛋白基因?qū)氲脚咛ジ杉毎M行表達,,再將其置于機械力作用下,,發(fā)現(xiàn)在磁珠作用下,細胞內(nèi)的綠色熒光逐漸消退,,這說明基因表達量降低,。(生物谷Bioon.com)
生物谷推薦原始出處:
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