Centripetal nuclear shape fluctuations associate with chromatin condensation towards mitosis

The cell nucleus plays a central role in several key cellular processes, including chromosome organisation, replication and transcription. Recent work intriguingly suggests an association between nuclear mechanics and cell-cycle progression, but many aspects of this connection remain unexplored. Here, by monitoring nuclear shape fluctuations at different cell cycle stages, we uncover increasing inward fluctuations in late G2 and early mitosis, which are initially transient, but develop into instabilities that culminate into nuclear-envelope breakdown in mitosis. Perturbation experiments and correlation analysis reveal an association of these processes with chromatin condensation. We propose that the contrasting forces between an extensile stress and centripetal pulling from chromatin condensation could link mechanically chromosome condensation and nuclear- envelope breakdown, the two main nuclear processes during mitosis. Significance StatementThe nucleus was recently shown to exhibit shape fluctuations that vary with cell-cycle stage, but we know very little about the possible links between nuclear mechanics and cell cycle- progression. Through flickering analysis, this study monitors radius and nuclear envelope fluctuations across the cell cycle. The authors discover that as the cell cycle progresses towards mitosis, localised inward invaginations of the nuclear shape form initially transiently and gradually increasing their amplitude, in association with chromatin condensation. This phenomenon develops into nuclear envelope breakdown, suggesting a novel link between cell cycle, chromatin mechanics and nuclear shape fluctuations.