Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells
Farhan Chowdhury,Sungsoo Na,Sungsoo Na,Dong Li,Yeh Chuin Poh,Tetsuya S. Tanaka,Fei Wang,Ning Wang +7 more
TLDR
It is shown that a local cyclic stress via focal adhesions induced spreading in mouse ES cells but not in mES cell-differentiated (ESD) cells that were 10-fold stiffer, demonstrating that cell softness dictates cellular sensitivity to force.Abstract:
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.read more
Citations
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Mechanical forces direct stem cell behaviour in development and regeneration
Kyle H. Vining,David J. Mooney +1 more
TL;DR: Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.
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Balancing forces: architectural control of mechanotransduction
TL;DR: Sustained disruptions in tensional homeostasis can be caused by alterations in the extracellular matrix, allowing it to serve as a mechanically based memory-storage device that can perpetuate a disease or restore normal tissue behaviour.
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Mechanical control of tissue and organ development
TL;DR: Work based on the convergence of physics, engineering and biology that suggests that mechanical forces generated by living cells are as crucial as genes and chemical signals for the control of embryological development, morphogenesis and tissue patterning is reviewed.
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The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β.
Jennifer Park,Julia S. Chu,Anchi D. Tsou,Anchi D. Tsou,Rokhaya Diop,Rokhaya Diop,Zhenyu Tang,Zhenyu Tang,Aijun Wang,Song Li,Song Li +10 more
TL;DR: Insight is provided of how substrate stiffness differentially regulates stem cell differentiation, and have significant implications for the design of biomaterials with appropriate mechanical property for tissue regeneration.
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Hydrodynamic stretching of single cells for large population mechanical phenotyping
Daniel R. Gossett,Henry T. K. Tse,Serena A. Lee,Yong Ying,Anne Lindgren,Otto O. Yang,Jianyu Rao,Amander T. Clark,Dino Di Carlo +8 more
TL;DR: An automated microfluidic technology capable of probing single-cell deformability at approximately 2,000 cells/s is demonstrated, bringing the statistical accuracy of traditional flow cytometric techniques to label-free biophysical biomarkers, enabling applications in clinical diagnostics, stem cell characterization, and single- cell biophysics.
References
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Matrix elasticity directs stem cell lineage specification.
TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
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Tissue Cells Feel and Respond to the Stiffness of Their Substrate
TL;DR: An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.
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Cell shape, cytoskeletal tension, and rhoa regulate stem cell lineage commitment
TL;DR: It is demonstrated that cell shape regulates commitment of human mesenchymal stem cells to adipocyte or osteoblast fate and mechanical cues experienced in developmental and adult contexts, embodied by cell shape, cytoskeletal tension, and RhoA signaling, are integral to the commitment of stem cell fate.
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In-Hyun Park,In-Hyun Park,Rui Zhao,Rui Zhao,Jason A. West,Jason A. West,Akiko Yabuuchi,Akiko Yabuuchi,Hongguang Huo,Hongguang Huo,Tan A. Ince,Paul H. Lerou,M. William Lensch,M. William Lensch,George Q. Daley,George Q. Daley +15 more
TL;DR: The data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.
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Mechanotransduction across the cell surface and through the cytoskeleton
TL;DR: The results suggest that integrins act as mechanoreceptors and transmit mechanical signals to the cytoskeleton, which may be mediated simultaneously at multiple locations inside the cell through force-induced rearrangements within a tensionally integrated cytos skeleton.