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- Title
Mechanical memory and dosing influence stem cell fate.
- Authors
Yang, Chun; Tibbitt, Mark W.; Basta, Lena; Anseth, Kristi S.
- Abstract
We investigated whether stem cells remember past physical signals and whether these can be exploited to dose cells mechanically. We found that the activation of the Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) as well as the pre-osteogenic transcription factor RUNX2 in human mesenchymal stem cells (hMSCs) cultured on soft poly(ethylene glycol) (PEG) hydrogels (Young's modulus E ~ 2 kPa) depended on previous culture time on stiff tissue culture polystyrene (TCPS; E ~ 3 GPa). In addition, mechanical dosing of hMSCs cultured on initially stiff (E ~ 10 kPa) and then soft (E ~ 2 kPa) phototunable PEG hydrogels resulted in either reversible or-above a threshold mechanical dose-irreversible activation of YAP/TAZ and RUNX2. We also found that increased mechanical dosing on supraphysiologically stiff TCPS biases hMSCs towards osteogenic differentiation. We conclude that stem cells possess mechanical memory-with YAP/TAZ acting as an intracellular mechanical rheostat-that stores information from past physical environments and influences the cells' fate.
- Subjects
STEM cell research; CELL determination; MESENCHYMAL stem cells; POLYETHYLENE glycol; COLLOIDS; TISSUE culture
- Publication
Nature Materials, 2014, Vol 13, Issue 6, p645
- ISSN
1476-1122
- Publication type
Article
- DOI
10.1038/nmat3889