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Nat Mater. 2014 Jun;13(6):645-52. doi: 10.1038/nmat3889. Epub 2014 Mar 16.

Mechanical memory and dosing influence stem cell fate.

Author information

1
1] Department of Chemistry and Biochemistry, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, USA [2].
2
1] Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, USA [2] [3].
3
Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, USA.
4
1] Department of Chemical and Biological Engineering, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, USA [2] Howard Hughes Medical Institute, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, USA [3] BioFrontiers Institute, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, USA.

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.

PMID:
24633344
PMCID:
PMC4031270
DOI:
10.1038/nmat3889
[Indexed for MEDLINE]
Free PMC Article

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