Multiscale Architecture and Mechanics of the Cell Nucleus: Implications for Disease, Bioengineering and Nanomedicine

ABSTRACT The cell nucleus serves as the central hub of genetic information and a dynamic, multiscale mechanosensor that regulates critical cellular behaviors, such as gene expression and cell migration. Functioning as a complex soft matter system, the nucleus comprises a hierarchical architecture spanning from nanoscale DNA and nucleosomes to microscale chromosome territories and the nuclear envelope. This multiscale structural organization endows the nucleus with scale‐dependent mechanical properties—such as stiffness and viscoelasticity—that are fundamental to cellular mechanotransduction and the strict regulation of nuclear entry for therapeutic nanoparticles. This review emphasizes the recent advances in understanding the multiscale architecture and mechanics of the cell nucleus. We compare experimental technologies for probing nuclear mechanics, alongside emerging multiscale theoretical models that transform these qualitative observations into quantitative, predictive frameworks for mechanobiology and nanomedicine. Finally, we highlight the translational implications of nuclear mechanics on nuclear‐targeted nanomedicine, mechanodiagnosis, and mechanotherapy.