Rupture Dynamics and Chromatin Herniation in Deformed Nuclei

During migration of cells in vivo, in both pathological processes such as cancer metastasis or physiological events such as immune cell migration through tissue, the cells must move through narrow interstitial spaces that can be smaller than the nucleus. This can induce deformation of the nucleus which, according to recent experiments, may result in rupture of the nuclear envelope that can lead to cell death, if not prevented or healed within an appropriate time. The nuclear envelope, which can be modeled as a double lipid bilayer attached to a viscoelastic gel (lamina) whose elasticity and viscosity primarily depend on the lamin composition, may utilize mechanically induced, self-healing mechanisms that allow the hole to be closed after the deformation-induced strains are reduced by leakage of the internal fluid. Here, we present a viscoelastic model of the evolution of a hole nucleated by deformations of the nuclear lamina and estimate the herniation of chromatin through the hole and its relation to the lamin expression levels in the nuclear envelope.