Harada et al. describe how nuclear lamins affect the ability of migrating cells to squeeze through tissues and survive the resulting stress.
Migrating cells must maneuver their large and chromatin-packed nuclei through tiny gaps in the surrounding tissue. A- and B-type lamins assemble in the nuclear periphery and help determine the organelle’s mechanical properties, but whether these proteins affect cell migration is unclear. Harada et al. tested the role of lamin-A in several different cell types.
Partially reducing lamin-A levels enhanced the ability of cells to move through extracellular matrix containing small, 3-µm pores, whereas overexpressing the protein inhibited cell migration. Cells that expressed stoichiometrically high amounts of lamin-B were particularly sensitive to changes in lamin-A levels.
The researchers found that nuclei containing low amounts of lamin-A were softer, allowing them to squeeze through tiny pores and—due to the spring-like properties of lamin-B—return to their normal shape on the other side. In contrast, high lamin-A levels made nuclei stiff and harder to maneuver, a property that could help keep mesenchymal stem cells, which express large amounts of lamin-A, anchored in their niche.
Nuclei can be too soft for their own good, however. Cells experience stress as they migrate through tissues, occasionally resulting in apoptosis. Cells lacking lamin-A were less resistant to stress and more prone to death, possibly because they expressed lower amounts of the chaperone HSP90. Senior author Dennis Discher now wants to investigate whether the need for HSP90 is merely an indicator of DNA damage that might accumulate as nuclei squeeze through tiny pores in solid tissues.
Text by Ben Short