Summary
The study investigates the relationship between matrix stiffness, nuclear deformation, and lamin A/C tension-dependent YAP nuclear localization. It finds that matrix stiffness drives drop-like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization.
Highlights
- Matrix stiffness influences cancer cell fate by altering gene expression.
- Nuclear lamin A/C exhibits mechanical threshold behavior and is inextensible once unwrinkled.
- A computational model predicts that the unwrinkled lamina is under tension.
- Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM.
- Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization.
- YAP nuclear localization is correlated with the unfolding of wrinkles in the nucleus.
- Lamin A/C is required for laminar surface tension and the sensitivity of YAP to laminar unfolding and cell spreading.
Key Insights
- The study reveals that the nuclear lamina assembles in a wrinkled state after mitosis, which is aligned with the drop model where the area of the lamina intrinsically exceeds the area of a sphere of the same volume.
- The unfolding of laminar wrinkles on stiff gels may be due to an increase in nuclear volume during culture after seeding on stiff gels or the unfolding of wrinkles as a rounded nucleus deviates from its shape.
- The study suggests that the lamina provides surface tension to the nuclear drop in cancer cell lines, which balances intranuclear pressure.
- The correlation between YAP localization to the nucleus and unwrinkling of the nucleus suggests a potential role for laminar tension in regulating YAP transport.
- The study finds that lamin A/C knockdown reduces the sensitivity of YAP N/C ratios to both cell spreading and EFC ratio in HN cells.
- The results are consistent with a model in which surface tension in the lamina, supported by lamin A/C networks, regulates YAP translocation to the nucleus.
- The study's findings connect cell shape-driven control of nuclear wrinkling to signaling and regulation of cell function, suggesting that the tension in the lamina has a role in regulating YAP transport.
Mindmap
Citation
Wang, T.-C., Abolghasemzade, S., McKee, B. P., Singh, I., Pendyala, K., Mohajeri, M., Patel, H., Shaji, A., Kersey, A. L., Harsh, K., Kaur, S., Dollahon, C. R., Chukkapalli, S., Lele, P. P., Conway, D. E., Gaharwar, A. K., Dickinson, R. B., & Lele, T. P. (2024). Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization. In Nature Communications (Vol. 15, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41467-024-54577-4