Cellular nuclear dynamics in response to envelope rupture

The nuclear envelope is a composite elastic membrane that encloses the genome and regulates nucleo-cytoplasmic exchange in eukaryotic cells. Subject to intrinsic and extrinsic mechanical stresses, the nuclear envelope can undergo transient rupture, leading to the leakage of chromatin into the cytoplasm. Such rupture has been implicated in DNA damage, particularly in cancer cells. Recovery involves retrieving the leaked chromatin and resealing the nuclear envelope—a process primarily driven by DNA-binding proteins that cross-link chromatin and promote its compaction. Motivated by experiments in which rupture is induced through mechanical compression or laser ablation, we develop a continuum model to study the dynamics of chromatin and cross-linking proteins following nuclear envelope rupture. Chromatin is coarse-grained as a polymeric gel that contracts in response to cross-linking interactions. The nuclear envelope is modeled as a thin elastic shell dynamically coupled to the gel. Cross-linker proteins are transported via advection, diffusion, and reversible binding, allowing them to accumulate at rupture sites and locally compact the chromatin. Our model captures the nonlinear interplay between gel mechanics, protein transport, and membrane elasticity. Numerical simulations reproduce the key dynamical behaviors observed in vivo during chromatin leakage and retrieval. We further show that severe rupture events can trigger global nuclear contraction and wrinkling of the nuclear envelope, consistent with experimental observations. Our study identifies and characterizes the physical mechanisms that govern chromatin recovery and reorganization following nuclear envelope rupture, highlighting the central role of cross-linking proteins in this process.