Plasticity in cell migration is crucial for tissue homeostasis but can also drive metastasis, and the ‘decision making’ mechanisms involved in different migration modes remain incompletely understood. The large, stiff nucleus becomes an obstacle during migration through narrow constrictions, and a cell must either apply forces to the nucleus to enable its transit or find an alternative route. Here (Keys et al., 2024), Jan Lammerding and colleagues test whether actomyosin contractility and cytoplasmic pressure in the rear cortex contribute to these forces. They find that whereas cancer cell lines with high migratory plasticity and mouse embryonic fibroblasts (MEFs), which have less plasticity, can both form a region of enrichment and local activation of actin and myosin II in the rear cortex while transiting narrow channels, this only results in faster nuclear transit in the cancer cell lines. Laser ablation of the rear cortex of transiting cancer cells causes the nucleus to move backwards, suggesting that actomyosin generates a local increase in pressure that pushes the nucleus forwards. Ablation of the cytoskeleton directly in front of the nucleus likewise causes the nucleus to move backwards, although to a lesser degree, implying that mechanical links between the nucleus and the cytoskeleton also pull the nucleus forward, as has previously been observed in MEFs. Cells capable of migratory plasticity might therefore be able to switch between cortex-driven ‘pushing’ and non-cortex-driven ‘pulling’ mechanisms to efficiently navigate different levels of confinement in complex environments.
