(134g) Dynamic Deformation of the Cell Plastically Shapes the Nucleus and Amplifies Cancer Nuclear Irregularities

Tocco, V. J. Jr., University of Florida
Li, Y., University of Florida
Dickinson, R., University of Florida
Lele, T., University of Florida
Shapes of cell nuclei normally conform to the overall cell shape. This conformity is commonly interpreted as the stiff nucleus being elastically deformed in response to static cytoskeletal stresses whose distribution on the nuclear surface depends on cell shape. However, we found that deformed shapes of nuclei removed from cells by microdissection were preserved, both for smooth, elongated nuclei in fibroblasts and irregularly shaped nuclei of breast cancer cells. The lack of shape relaxation implies that nuclear deformations are plastic and the cellular stresses that deform the nucleus are dissipative, not static. Tracking changes of nuclear and cellular shape on micropatterned substrata revealed that fibroblast nuclei deform only during deformations in cell shape and only in the direction of nearby moving cell boundaries. Nuclear shape irregularities in MDA-MB-231 cancer cells increased during dynamic cell spreading, but decreased in MCF-10A cells. Furthermore, nuclear irregularities of cancer cells were reduced upon the disruption of the LINC complex. Elastic deformation of the cancer cell nucleus caused by a direct nuclear force probe did not correlate with its irregularity, nor with changes in irregularity upon perturbations to the nuclear envelope. We propose that the nucleus in a cell undergoing changes in shape is plastically deformed by dissipative stresses transmitted through the cytoplasm from the moving cell boundary to the nuclear surface.