Abstract
As cells move from two-dimensional surfaces into complex 3D environments, the nucleus becomes a barrier to movement due to its size and rigidity. Therefore, moving the nucleus is a key step in 3D cell migration. In this review, we discuss how coordination between cytoskeletal and nucleoskeletal networks is required to pull the nucleus forward through complex 3D spaces. We summarize recent migration models which utilize unique molecular crosstalk to drive nuclear migration through different 3D environments. In addition, we speculate about the role of proteins that indirectly crosslink cytoskeletal networks and the role of 3D focal adhesions and how these protein complexes may drive 3D nuclear migration.