Active Chromatin Dynamics Drives Nuclear Bulge Formation

The cell nucleus is an active complex environment containing long chains of DNA polymers transcribed by molecular motors. Intriguingly, we have observed that the genomic process of transcription can generate irregular nuclear protrusions called blebs, but how this morphological change occurs is not understood. We have developed a three-dimensional Brownian-dynamics-based model of a nucleus consisting of a polymeric protein shell (the lamina), a crosslinked polymer chain (chromatin), and extensive and contractile motors representing transcription and other nonequilibrium genomic processes. In simulations, we observe localized bulges on the nuclear surface, indicating the possible formation of blebs or their precursors. The number and size of these bulges grow as the number of motors and their strength increase. The model also captures mechanical properties, such as the compression-stiffening behavior of the nucleus. Nuclei respond to applied compression in a rate-dependent manner. With slow deformations, the nucleus maintains an ellipsoidal shape, whereas we observe large wrinkles, folds, and bulges with faster compression. Therefore, our model captures the cell nucleus's mechanical, morphological, and dynamical properties and demonstrates how both passive and active mechanisms can shape cellular structures.