Stress transmission towards the nucleus of the cell

Cells constantly experience mechanical forces from their microenvironment, positioning the nucleus as a central integrator of physical cues and gene regulatory programs. This review examines current evidence on how mechanical signals are transmitted from the extracellular matrix to the nucleus and how key nuclear structures respond in a context-dependent manner. The perinuclear cytoskeletal components-such as the actin cap, microtubules, and the Ca²⁺-INF2 signaling axis-are discussed as key transducers that regulate nuclear morphology and facilitate mechanosensitive nucleocytoplasmic transport. The linker of nucleoskeleton and cytoskeleton (LINC) complex is highlighted as a major conduit for conveying cytoskeletal forces across the nuclear envelope. Within the nucleus, the nuclear pore complex exhibits mechanoresponsive behavior that may modulate molecular flux and contribute to structural resilience. The nuclear lamina acts as a load-bearing scaffold associated with nuclear stiffness regulation and chromatin organization. Chromatin itself undergoes force-associated structural and epigenetic remodeling, and mechanosensitive transcription factors-including, but not limited to, Yes-associated protein and transcriptional co-activator with PDZ-binding motif (YAP/TAZ)-have been implicated in linking mechanically altered nuclear states to gene expression responses. Advances in high-resolution imaging and novel force-probing technologies are further illuminating the dynamics of nuclear mechanics. Together, current findings outline an evolving framework for understanding how extracellular mechanics interface with nuclear structure and gene regulation in health and disease.