The nucleus is irreversibly shaped by motion of cell boundaries in cancer and non‐cancer cells

• Published in: Journal of cellular physiology 2018-02, Vol.233 (2), p.1446-1454
• Main Authors: Tocco, Vincent J., Li, Yuan, Christopher, Keith G., Matthews, James H., Aggarwal, Varun, Paschall, Lauren, Luesch, Hendrik, Licht, Jonathan D., Dickinson, Richard B., Lele, Tanmay P.
• Format: Article
• Language: English
• Subjects: Actomyosin; Animals; Boundaries; Breast cancer; Breast Neoplasms - pathology; Cancer; cell forces; Cell Line, Tumor; Cell Movement; Cell Nucleus - pathology; Cell Nucleus Shape; Cell Shape; Cell size; Cell spreading; Dissection; Elastic deformation; Elongation; Energy Transfer; Female; Fibers; Fibroblasts; Fibroblasts - cytology; Humans; Mechanotransduction, Cellular; Mice; NIH 3T3 Cells; nuclear mechanics; nuclear shape; Nuclei; Nuclei (cytology); Stress Fibers - pathology; Stress, Mechanical; Time Factors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26031

Actomyosin stress fibers impinge on the nucleus and can exert compressive forces on it. These compressive forces have been proposed to elongate nuclei in fibroblasts, and lead to abnormally shaped nuclei in cancer cells. In these models, the elongated or flattened nuclear shape is proposed to store elastic energy. However, we found that deformed shapes of nuclei are unchanged even after removal of the cell with micro‐dissection, both for smooth, elongated nuclei in fibroblasts and abnormally shaped nuclei in breast cancer cells. The lack of shape relaxation implies that the nuclear shape in spread cells does not store any elastic energy, and the cellular stresses that deform the nucleus are dissipative, not static. During cell spreading, the deviation of the nucleus from a convex shape increased in MDA‐MB‐231 cancer cells, but decreased in MCF‐10A cells. 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. We propose that motion of cell boundaries exert a stress on the nucleus, which allows the nucleus to mimic cell shape. The lack of elastic energy in the nuclear shape suggests that nuclear shape changes in cells occur at constant surface area and volume. In many models of nuclear shaping in adherent cells, nuclear deformations (flattened or elongated shapes) are proposed to store elastic energy. However, in this work, we found that there was no elastic relaxation after removing deformed nuclear shapes out of cells, implying no storage of elastic energy. We propose that motion of nearby cell boundaries exert irreversible stresses on the nucleus to change its shape.