Analytical Sciences

Designing Elastic Modulus of Cell Culture Substrate to Regulate YAP and RUNX2 Localization for Controlling Differentiation of Human Mesenchymal Stem Cells

Masashi YAMAZAKI,* Satoru KIDOAKI,** Hiromichi FUJIE,* and Hiromi MIYOSHI*

*Mechanical Systems and Engineering, Graduate School Systems Design, Tokyo Metropolitan University, 1-1 Minamiosawa, Hachioji, Tokyo 192-0397, Japan
**Laboratory of Biomedical and Biophysical Chemistry, Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi, Fukuoka 819-0395, Japan

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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