A mechanochemical model for dynamic deformation and adaptive stiffening of cell nuclei

Cell nuclei constantly experience intracellular and extracellular forces, which can significantly influence nuclear morphologies, structures, and functions. Lamin proteins, as a structural component of the nuclear envelope, are mechanosensitive and can remodel to change the rigidity of the nuclear envelope through reaction–diffusion dynamics, displaying intricate mechanochemical interplay. Here, we propose a mechanochemical model to investigate the adaptive dynamics of cell nuclei under mechanical forces. We show that localized pushing forces may cause nuclear invagination while trigger lamin assembly or disassembly, depending on the mechanosensitivity of cells. This mechanochemical remodeling enables nuclei to stiffen adaptively, preventing large deformation and rupture. The loading timescale is found to influence nuclear dynamics, where active nuclear stiffening takes place when the external loading rate is comparable to or slower than the mechanosensitive response rate of lamins. Moreover, the mechanical properties of chromatin significantly contribute to nuclear responses. Our results explain morphological evolution and lamin dynamics observed in nuclear experiments and could provide a framework for decoding the mechanochemical mechanisms in nuclear responses and other physiological processes.