Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells.
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.
Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Illinois 61801, USA.
Farhan
F
Chowdhury
Sungsoo
S
Na
Dong
D
Li
Yeh-Chuin
YC
Poh
Tetsuya S
TS
Tanaka
Fei
F
Wang
Ning
N
Wang
D000199:Actins / Q000378:metabolism; D000818:Animals; D001703:Biophysics / Q000379:methods; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004548:Elasticity; D053595:Embryonic Stem Cells / Q000166:cytology*; D022001:Focal Adhesions; D051379:Mice; D024462:Myosin Type II / Q000737:chemistry; D010766:Phosphorylation; D013314:Stress, Mechanical; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D019061:src-Family Kinases; D024462:Myosin Type II; D020764:cdc42 GTP-Binding Protein