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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
