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Mechanical memory and dosing influence stem cell fate.

Chun Yang1, Mark W Tibbitt2, Lena Basta3

  • 11] Department of Chemistry and Biochemistry, University of Colorado Boulder, 3415 Colorado Avenue, Boulder, Colorado 80303, USA [2].

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Summary
This summary is machine-generated.

Stem cells exhibit mechanical memory, retaining information about past physical environments. This memory, mediated by YAP/TAZ proteins, influences cell fate and can be manipulated for mechanical dosing.

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Stem Cell Biology

Background:

  • Stem cell differentiation is influenced by the physical properties of their microenvironment.
  • The role of mechanical memory in stem cell fate decisions remains incompletely understood.

Purpose of the Study:

  • To investigate if stem cells possess a memory of past physical signals.
  • To explore the potential for mechanical dosing to influence stem cell fate through this memory.

Main Methods:

  • Human mesenchymal stem cells (hMSCs) were cultured on soft poly(ethylene glycol) (PEG) hydrogels and stiff tissue culture polystyrene (TCPS).
  • Activation of Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding domain (TAZ) and RUNX2 was monitored.
  • Phototunable PEG hydrogels were used for mechanical dosing experiments.

Main Results:

  • hMSC activation of YAP/TAZ and RUNX2 depended on prior culture on stiff TCPS before soft PEG hydrogels.
  • Mechanical dosing on phototunable hydrogels led to reversible or irreversible YAP/TAZ and RUNX2 activation.
  • Increased mechanical dosing on stiff TCPS promoted osteogenic differentiation in hMSCs.

Conclusions:

  • Stem cells possess a mechanical memory, storing information from past physical environments.
  • YAP/TAZ proteins act as an intracellular mechanical rheostat, mediating this memory.
  • Mechanical memory in stem cells influences their differentiation fate and can be exploited for mechanical dosing.