CHE SEMINAR: Morphodynamics of the cell nucleus

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Title: Morphodynamics of the cell nucleus

Abstract: The shape of the cell nucleus is closely related to cell function. Nuclear shape reflects its state of mechanical stress, which can affect cell signaling and gene expression or cause nuclear rupture and DNA damage. Extreme nuclear deformation is required for normal or cancer cells to migrate through tight constrictions in tissues. Moreover, pathologists use irregular nuclear shapes as a marker to grade cancer malignancy. A deformed nuclear shape is widely assumed to arise from a balance between cytoskeletal stresses and the elastic deformation of the nucleus from a spherical resting state, but our experimental and theoretical studies challenge this assumption and point to a much different model for how nuclear shapes are established. Nuclei are not normally spherical; even in rounded cells, the nuclear lamina typically has surface folds and undulations that indicate a significantly larger surface area than needed for a sphere of the same volume. Geometrically, excess surface area permits a wide range of shape changes with for the same surface area and volume, and only when the nucleus becomes so deformed that the lamina becomes smoothed and tensed does it take on a limiting shape where further deformation requires areal expansion of the lamina or compression of the nuclear volume. The nucleus in rounded cells is therefore highly compliant to stress transmitted through the cytoskeleton, allowing nuclear shape changes mirrors the cell shape changes. However, in highly deformed nuclei where the lamina becomes smooth and tensed, the nuclear shape can be entirely predicted from the cell boundaries and the geometric constraints of constant lamina area, cell volume, and nuclear volume. Importantly, observed nuclear shapes can be predicted independent of the elastic or viscoelastic properties of the cell and nucleus. This principle has been demonstrated in various contexts, including in cells spread on a surface, in monolayers, on rectangles with various aspect ratios, confined to a well, or with nuclei indented by obstacles. Our results show that nuclear shapes in spread cells are primarily determined by geometry, not mechanics, and that lamina excess area is an essential parameter to consider when modeling nuclear deformation or inferring nuclear stress (and affected mechanosensitive cell signaling pathways) from the extent of nuclear deformation.

Bio: Dr. Dickinson joined the UF Chemical Engineering Department in 1994. He is a Fellow of AICHE and of AIMBE. Dr. Dickinson served as Department Chair from 2009-2017 before serving a four-year rotation as Director of the Chemical, Bioengeering, Environmental and Transport Systems (CBET) Division at the National Science Foundation. His research interests are primarily in the areas of cellular engineering and cell mechanics, with current focus on computational cell and tissue morphodynamics.