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Mechanical memory and dosing influence stem cell fate

Nature Materials, ISSN: 1476-4660, Vol: 13, Issue: 6, Page: 645-652
2014
  • 868
    Citations
  • 0
    Usage
  • 1,229
    Captures
  • 0
    Mentions
  • 75
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    868
  • Captures
    1,229
  • Social Media
    75
    • Shares, Likes & Comments
      75
      • Facebook
        75

Article Description

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. © 2014 Macmillan Publishers Limited.

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