Cells migrating through confined spaces, such as tumour cells during metastasis, experience mechanical stress that disproportionally deforms the nucleus, which is the largest and stiffest organelle. Whereas this deformation is known to impact chromatin and the nuclear lamina, its effects on nuclear structures such as biomolecular condensates remain unclear. Zhao et al. show that chromatin-embedded condensates in the advancing and the trailing halves of the nucleus respond differently to constricted migration.

Deformation also altered local chromatin organization. Analysis of the intensity of fluorescent protein-tagged histone H2B revealed that the trailing half of the nucleus displayed higher chromatin heterogeneity (that is, a mix of chromatin-poor and chromatin-dense regions) compared with the advancing half, suggesting that the two nuclear parts have distinct mechanical environments. Increased chromatin heterogeneity created open, that is, chromatin-depleted, regions that are more permissive to condensate formation, thus favouring phase separation in the trailing half of the migrating nucleus.