Assays to measure nuclear mechanics in interphase cells

The nucleus is the characteristic hallmark of all eukaryotic cells. The physical properties of the nucleus reflect important biological characteristics, such as chromatin organization or nuclear envelope composition; they can also directly affect cellular function, e.g., when cells pass through narrow constrictions, where the stiff nucleus may present a limiting factor. We present two complementary techniques to probe the mechanical properties of the nucleus. In the first, nuclear stiffness relative to the surrounding cytoskeleton is inferred from induced nuclear deformations during strain application to cells on an elastic substrate. In the second approach, nuclear deformability is deduced from the transit time through a perfusion-based microfabricated device with constrictions smaller than the size of the nucleus. These complementary methods, which can be applied to measure nuclear stiffness in large numbers of living adherent or suspended cells, can help identify important changes in nuclear mechanics associated with disease or development.