Font Size: 

The mechanical response of the cell nucleus is thought to depend on chromatin within the nucleoplasm, the nuclear envelope, and the nuclear lamina underlying the envelope. In this study, we performed Brownian dynamics simulations of nuclear tensile deformation to investigate how these intranuclear structures collectively determine the overall mechanical properties of the nucleus. We represented 46 chromatin fibers, classified into condensed and decondensed states, using a bead-spring model. This chromatin model was then integrated with a nuclear envelope model representing the mesh structure of the nuclear lamina to construct a whole nucleus model. The simulation results demonstrated that both the interactions between the nuclear envelope and condensed chromatin and the interactions arising from the crosslinking between condensed chromatin regions contribute to the tensile resistance of the nucleus, in addition to the intrinsic contributions of chromatin and the nuclear envelope themselves. Notably, these condensed chromatin-related interactions enhanced nuclear deformation resistance only when both types of interactions were simultaneously present. Furthermore, the TSA-treated nucleus model, consisting solely of decondensed chromatin fibers, exhibited mechanical softening compared with the untreated nucleus, which contained both condensed and decondensed chromatin fibers. This softening arose from the loss of the two condensed chromatin-related interactions. The simulated tensile mechanical properties and TSA-induced nuclear softening were consistent with previously reported experimental observations.