(596v) Nuclear Mechanics in Crawling Cells

On cellular length scales, the nucleus is massive (~10-15 microns in diameter) and stiff relative to the cytoplasm. Motion of such a large object in the crowded intracellular space requires a significant expenditure of energy and hence represents a significant task for the motile cell. Currently, one of the basic questions is whether the nucleus is primarily “pushed” into position by compressive cytoskeletal forces, or “pulled” by tensile cytoskeletal forces. In this study, we show that the nucleus in a single, polarized crawling fibroblast is pulled forward toward the leading edge. The pulling forces originate from actomyosin contraction between the leading edge and the nuclear surface; these forces are opposed by actomyosin pulling in the trailing edge. Microtubules serve to damp fluctuations in nuclear position, but are not required for directional nuclear motion. Our results indicate that the nucleus is under net tension in a crawling cell due to a competition between actomyosin pulling from the front and back of the crawling cell. This work offers new insight into force generation on the nucleus in migrating cells.