Elucidating the short and long-term mechanical response of the cell nucleus with a hybrid viscoelastic model

The mechanical properties of the nucleus play an important role in all the processes of a cell and impact greatly its decisions, functions and phenotype. It is then important to understand how internal and external stresses can modify them. To study the mechanical response of the nucleus at different timescales, a hybrid viscoelastic model integrating both continuum mechanics and soft glass matter theory is developed. It indeed accounts for the instantaneous viscoelastic response of the structural components of the nucleus as well as the active response of the nuclear envelope and the dynamic reorganization of the cytoskeleton at different timescales. This model can describe adequately the nuclear deformation caused by substrate stiffness in primary hepatocytes and HepG2 cells in culture up to 5 days. It also reveals that the increase of nuclear strain in the long term implies nuclear softening (a phenomenon intensified on stiffer substrates), simultaneously with an increase of the dissipative properties of the nucleus, offering stability. Finally, in the context of soft glassy theory, the model suggests that processes of aging and mechanical memory of the cell may be originated by the dissipative capacity of the nuclei.