TY - JOUR
T1 - Designing Elastic Modulus of Cell Culture Substrate to Regulate YAP and RUNX2 Localization for Controlling Differentiation of Human Mesenchymal Stem Cells
AU - YAMAZAKI, Masashi
AU - KIDOAKI, Satoru
AU - FUJIE, Hiromichi
AU - MIYOSHI, Hiromi
N1 - Funding Information:
This work was supported by JSPS KAKENHI (grant number JP19J13048) and AMED (grant number 18gm5810012h9904).
Publisher Copyright:
© 2021. All rights reserved.
PY - 2021
Y1 - 2021
N2 - To establish a guideline for the design of cell culture substrates to control human mesenchymal stem cell (MSC) differentiation, we quantitatively characterized the heterogeneity in the responsiveness of MSCs to the elastic modulus of culture substrates. We analyzed the elastic modulus-dependent dynamics of a mechanotransducer, YAP, and an osteogenic differentiation factor, RUNX2, in three different MSC lots using a styrenated gelatin gel with controllable elastic modulus. The percentage of cells with YAP in the nucleus increased linearly with increases in the elastic modulus, reaching a plateau at 10 kPa for all the lots analyzed. The increase in the percentage with the substrate elastic modulus was described by the same linear function. The percentage of cells with RUNX2 nuclear localization also increased linearly with increases in the substrate elastic modulus, plateauing at 5 kPa, although the regression lines to the linearly increasing regions varied between lots. These similarities and differences in YAP and RUNX2 dynamics among cell populations are basis to design the substrate elastic modulus to manipulate YAP and RUNX2 localizations.
AB - To establish a guideline for the design of cell culture substrates to control human mesenchymal stem cell (MSC) differentiation, we quantitatively characterized the heterogeneity in the responsiveness of MSCs to the elastic modulus of culture substrates. We analyzed the elastic modulus-dependent dynamics of a mechanotransducer, YAP, and an osteogenic differentiation factor, RUNX2, in three different MSC lots using a styrenated gelatin gel with controllable elastic modulus. The percentage of cells with YAP in the nucleus increased linearly with increases in the elastic modulus, reaching a plateau at 10 kPa for all the lots analyzed. The increase in the percentage with the substrate elastic modulus was described by the same linear function. The percentage of cells with RUNX2 nuclear localization also increased linearly with increases in the substrate elastic modulus, plateauing at 5 kPa, although the regression lines to the linearly increasing regions varied between lots. These similarities and differences in YAP and RUNX2 dynamics among cell populations are basis to design the substrate elastic modulus to manipulate YAP and RUNX2 localizations.
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U2 - 10.2116/analsci.20SCP02
DO - 10.2116/analsci.20SCP02
M3 - Article
C2 - 33692265
AN - SCOPUS:85102826199
VL - 37
SP - 447
EP - 453
JO - Analytical Sciences
JF - Analytical Sciences
SN - 0910-6340
IS - 3
ER -