FIGURE 5:

Alterations of chromatin-based nuclear rigidity affect nuclear blebbing and morphology, independent of lamin perturbation. (A) Side view depiction of force balance between actin confinement and chromatin-based nuclear rigidity. (B) Top view, weakening of the nuclear spring constant through chromatin decompaction via increased euchromatin or decreased heterochromatin causes the nucleus to herniate at the major axis pole. (C) Strengthening of the nuclear spring constant through chromatin compaction via increased heterochromatin partially rescues nuclear morphology observed in nuclei depleted of lamin B1. Similarly, chromatin compaction rescues nuclear morphology in nuclei overexpressing the mutant version of lamin A termed progerin that is associated with the accelerated aging disease HGPS. Chromatin compaction through increased heterochromatin also rescues nuclear morphology by both decreasing nuclear blebs and abnormally shaped nuclei in HGPS patient cells.