Physical plasticity of the nucleus and its manipulation.

The genome is virtually identical in all cells within an organism, with epigenetic changes contributing largely to the plasticity in gene expression during both development and aging. These changes include covalent modifications of chromatin components and altered chromatin organization as well as changes in other nuclear components, such as nuclear envelope lamins. Given that DNA in each chromosome is centimeters long and dozens of chromosomes are compacted into a microns-diameter nucleus through non-trivial interactions with the bounding envelope, the polymer physics of such a structure under stress can be complex but perhaps systematic. We summarize micromanipulation methods for measuring the physical plasticity of the nucleus, with recent studies documenting the extreme flexibility of human embryonic stem cells and the rigidification in model aging of progerin-type nuclei. Lamin-A/C is a common molecular factor, and methods are presented for its knockdown and measurement.