Journal
ANALYTICAL SCIENCES
Volume 37, Issue 3, Pages 447-453Publisher
JAPAN SOC ANALYTICAL CHEMISTRY
DOI: 10.2116/analsci.20SCP02
Keywords
Mesenchymal stem cell; styrenated gelatin gel; elastic modulus; mechanotransduction; heterogeneity
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Funding
- JSPS KAKENHI [JP19J13048]
- AMED [18gm5810012h9904]
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The study quantitatively characterized the responsiveness of MSCs to the elastic modulus of culture substrates through analyzing the dynamics of YAP and RUNX2. It was found that the percentage of MSCs with YAP and RUNX2 nuclear localization linearly increased with the increase in substrate elastic modulus, reaching a plateau at certain values. The similarities and differences in YAP and RUNX2 dynamics among MSC populations provide a basis for designing culture substrates to manipulate their localizations.
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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