Mechanical Forces and the Nucleolus: A New Frontier in Cellular Mechanotransduction

The nucleolus, traditionally viewed as the site of ribosome biogenesis, is now recognized as a multifunctional organelle involved in stress sensing, genome regulation, and cellular homeostasis. In parallel, mechanical cues arising from neighboring cells, extracellular matrix, and fluid flow have emerged as key regulators of development, tissue remodeling, and disease initiation and progression.These biophysical cues are transmitted to the nucleus through integrin, LINC complex-dependent pathways that modulate nuclear architecture, lamin organization, and chromatin structure. Because the nucleolus is embedded in a mechanically responsive environment and interacts directly or indirectly with the surrounding components, it is increasingly considered a potential target for mechanical cues. However, direct experimental evidence linking defined mechanical cues to nucleolar structure, phase behavior, and function remains limited. This review summarizes current knowledge on the emerging interface between nucleolus and mechanobiology, highlighting potential molecular pathways that connect force transmission to the nuclear response, and outlines unanswered questions relevant to development and disease.