Much of the structural stability of the nucleus comes from meshworks of
intermediate filament proteins known as
lamins forming the inner layer of the nuclear envelope called the nuclear lamina. These
lamin meshworks additionally play a role in gene expression. Abnormalities in nuclear shape are associated with a variety of pathologies, including some forms of
cancer and
Hutchinson-Gilford Progeria Syndrome, and often include protruding structures termed nuclear
blebs. These nuclear
blebs are thought to be related to pathological gene expression; however, little is known about how and why
blebs form. We have developed a minimal continuum elastic model of a
lamin meshwork that we use to investigate which aspects of the meshwork could be responsible for
bleb formation. Mammalian
lamin meshworks consist of two types of
lamin proteins, A type and B type, and it has been reported that nuclear
blebs are enriched in A-type
lamins. Our model treats each
lamin type separately and thus, can assign them different properties. Nuclear
blebs have been reported to be located in regions where the fibers in the
lamin meshwork have a greater separation, and we find that this greater separation of fibers is an essential characteristic for generating nuclear
blebs. The model produces structures with comparable morphologies and distributions of
lamin types as real pathological nuclei. Thus, preventing this opening of the meshwork could be a route to prevent
bleb formation, which could be used as a potential
therapy for the pathologies associated with nuclear
blebs.