4DCELL DEVICE

Microchannels

READ-OUTS

Nuclear membrane rupture, nuclear membrane re-sealing, nuclear deformation, gene expression, etc.

STANDARD CULTURE LIMITATION

In standard cultures, cell migration plays a key role both in physiological and pathological conditions. In these types of processes, both the cell body and nucleus experience severe confinement conditions, since they need to adapt to the external geometrical constraints imposed by their environment.  However, there is an enormous difficulty to reproduce and accurately control such complex conditions in 3D matrices, while keeping the ability to image and track the cells.

CELL NUCLEUS SQUEEZING ASSAY

When cells are cultured in microchannels, the cells behavior can be tracked, and it enables the acquisition of high-resolution images.

EXAMPLES

Nuclear deformation during cell migration leads to transient opening of the nuclear envelope [1]

• The ESCRT III complex, (similarly to what happens at mitotic exit) is required for fast resealing of the nucleocytoplasmic barrier.
• The transient opening leads to nucleo-cytoplasmic mixing (potentially causing DNA damage).

These events foster genetic disorders (as laminopathy) and also help explaining the migration ability of immune and cancerous cells.

Opening of the nucleo-cytoplasmic barrier during HeLa cell migration through a constriction

REFERENCE

[1] Raab, M., et al. (2016). Science, 352(6283), 359-362.