The actin protrusion deforms the nucleus during invasion through basement membrane

Cell invasion through basement membrane (BM) extracellular matrix barriers is important during organ development, immune cell trafficking, and cancer metastasis. Here we study an invasion event, anchor cell (AC) invasion, which occurs during Caenorhabditis elegans development. The actin protrusion of the invading AC mechanically displaces the BM, but it is not known how forces are balanced to prevent the growing actin protrusion from pushing itself backward when confronted with a load. Here we observe that the distal end of the actin protrusion in the invading AC abuts the nucleus and deforms it. Further we show that there is a correlation between invasion efficiency and nuclear deformation: under mutant conditions where invasion is reduced, nuclear deformation is diminished. However, nuclear deformation and invasion are unaffected by interfering with the molecular connections between the actin and microtubule cytoskeletons and the nuclear envelope. Together these data suggest that the AC actin protrusion braces against the nucleus to apply forces during invasion, but that nucleus-cytoskeleton molecular connections are not necessary for this to occur.

Actin-based membrane protrusions in invading cells apply force to basement membrane (BM) barriers to help break through them. In cell motility in 2D, the actin protrusion uses cell-substrate adhesions for leverage to push forward against obstacles in what is known as the molecular clutch. The situation is different in 3D invasion, where the adhesive substrate is being effaced by the invading cell. It is not clear, in this case, why the growing actin protrusion doesn't push itself backwards instead of extending forwards through the BM. The data presented here provide evidence that the distal end of the invasive actin protrusion is braced against the stiff, immobile nucleus, allowing growth of the proximal end to apply force on the BM.