Figure 5. Nucleus-cytoskeleton connections are essential to 3D migration.

(A) and (B). Cartoons of 3D embedded cells (A) with and (B) without Lamin A/C. Cells expressing lamin A/C are able to able to support actin-based protrusions and pulling because of intact nucleo-cytoskeletal connections. In cells devoid of lamin A/C, actin filaments are no longer held in place at the nuclear envelope by LINC complexes, removing nuclear support of actin-based movement. (C). Modeling the actin fibers in a cell on a 2D substrate. Lamellipodial protrusions are supported by connections to the stiff collagen-coated glass substrate. (D). Modeling the actin fibers in a cell embedded in a soft 3D matrix. Protrusions are supported by nucleo-cytoskeletal (N–S) connections in cells with intact LINC complexes. (E). For cells embedded in a 3D matrix without intact LINC complexes, the cell is unable to sustain protrusions as actin fibers are pushing through a soft matrix.