TY - JOUR
T1 - Substrate Stiffness Controls the Cell Cycle of Human Mesenchymal Stem Cells Via Cellular Traction
AU - Kureel, Sanjay Kumar
AU - Sinha, Shatarupa
AU - Purkayastha, Purboja
AU - Barretto, Sarah
AU - Majumder, Abhijit
N1 - Funding Information:
AM acknowledges the Wadhwani Research Centre for Bioengineering, IIT Bombay, India and Wellcome Trust-DBT India Alliance (Project #IA/E/11/1/500419) for research support. SS thanks IIT Bombay for her Post-Doctoral Fellowship. We thank Dr. James P Butler (Harvard Medical School, Department of Medicine, Boston) for his TFM codes, and Dr. Jyotsna Dhawan, InStem, for generously donating the C2C12 and 3T3 Cells. The authors aclnowledge the central microscopy facility of IIT Bombay.
Publisher Copyright:
© 2022, The Minerals, Metals & Materials Society.
PY - 2022/9
Y1 - 2022/9
N2 - The microenvironment of human mesenchymal stem cells (hMSCs) regulates their self-renewal and differentiation properties. Previously, it was shown that hMSCs remain quiescent on soft (0.25 kPa) polyacrylamide (PA) gels, but re-enter the cell cycle on a stiff (7.5 kPa) gel. However, how cells behave on intermediate stiffness and what intracellular factors transmit mechanical changes to cell interior, thereby regulating cell cycle, remained unknown. In this work, we have demonstrated that PA gels of stiffness between 1 kPa and 5 kPa act as a mechanical switch from quiescence to proliferation in the cell cycle of hMSCs. Further studies with ROCK inhibitor Y-27632 have revealed that contractile proteins, but not cell spread area, account for the sensitivity of hMSCs towards substrate stiffness, and hence correlates with their changes in cell cycle. These observations therefore suggest that substrate stiffness regulates hMSC proliferation through contractile forces, as generated by cellular contractile proteins in a unique pattern that is distinct from the two other cell types studied here, C2C12 and 3T3.
AB - The microenvironment of human mesenchymal stem cells (hMSCs) regulates their self-renewal and differentiation properties. Previously, it was shown that hMSCs remain quiescent on soft (0.25 kPa) polyacrylamide (PA) gels, but re-enter the cell cycle on a stiff (7.5 kPa) gel. However, how cells behave on intermediate stiffness and what intracellular factors transmit mechanical changes to cell interior, thereby regulating cell cycle, remained unknown. In this work, we have demonstrated that PA gels of stiffness between 1 kPa and 5 kPa act as a mechanical switch from quiescence to proliferation in the cell cycle of hMSCs. Further studies with ROCK inhibitor Y-27632 have revealed that contractile proteins, but not cell spread area, account for the sensitivity of hMSCs towards substrate stiffness, and hence correlates with their changes in cell cycle. These observations therefore suggest that substrate stiffness regulates hMSC proliferation through contractile forces, as generated by cellular contractile proteins in a unique pattern that is distinct from the two other cell types studied here, C2C12 and 3T3.
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U2 - 10.1007/s11837-022-05392-z
DO - 10.1007/s11837-022-05392-z
M3 - Article
AN - SCOPUS:85134054064
SN - 1047-4838
VL - 74
SP - 3419
EP - 3427
JO - Journal of Metals
JF - Journal of Metals
IS - 9
ER -