Mechanical memory and dosing influence stem cell fate

By Chun Yang, M. Tibbitt, L. Basta, K. Anseth. Nature Materials, 2014

1,040 citations recorded by the source corpus.

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 prior culture time on stiff tissue culture polystyrene (TCPS; E ~ 3 GPa). Additionally, 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 toward 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.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9d564af44f638f0fec699a2ba5a918855d9af895

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In Cell Biology

1. Jason A. Burdick
2. S. Caliari
3. A. Caplan
4. Dennis E. Discher
5. R. Fässler
6. Sigrid A. Langhans
7. A. Engler

In Molecular Biology

1. A. Caplan
2. Jason A. Burdick
3. J. Hare
4. Dennis E. Discher
5. R. Fässler

Citations in the corpus

• Mesenchymal stem cell perspective: cell biology to clinical progress (2019, background): “Growing MSCs for a longer time on either a soft or a stiff substrate progressively commits the cells to the corresponding lineages, making them refractory to rapid lineage switching by both soluble factors and substrate changes.(96,99) The molecular basis for this commitment— be it DNA methylation, ”
• A practical guide to hydrogels for cell culture (2016, background): “…influence on cell behavior, lung fibroblasts grown on stiff substrates undergo myofibroblast differentiation and retain a contractile phenotype even when later moved to soft substrates 9 , implying that cells retain memory of past mechanical environments 10 , which may bias subsequent experiments.”
• Integrin-mediated mechanotransduction (2016, background): “Forces in the piconewton range lead to the stretching of the talin rod and the exposure (and activation) of the cryptic VBS in the R2R3 domain (del Rio et al., 2009; Yao et al., 2014).”