Dimensionality affects nucleolar structure and cellular responses

Dimensionality profoundly influences how cells sense and respond to their physical environment. Even when exposed to the same physical factor—such as substrate stiffness—cells cultured in two-dimensional (2D) and three-dimensional (3D) environments often exhibit distinct behaviors. This discrepancy highlights a key knowledge gap in our current understanding of mechanobiology. To address this, my lab developed spherical microwells as a controllable 3D cell culture platform. Using this system, we observed dimensionality-dependent differences in cellular behaviors, including cell cycle progression and lineage commitment. Extending our analysis to the nuclear level, we found that cells in 2D typically contain multiple nucleoli, whereas cells in 3D tend to exhibit a single, larger nucleolus. These findings suggest that nuclear and nucleolar organization may underlie the distinct cellular behaviors observed between 2D and 3D environments.