Mechanobiology of the Nucleolus

Ribosome biogenesis is an essential and energy-demanding process required to maintain cellular proteostasis. The nucleolus, which orchestrates this vital process, assembles as a nuclear condensate and exhibits remarkable plasticity in its structure, function, and protein composition. This dynamic membraneless organization of the nucleolus contributes to its involvement in diverse signaling pathways, influencing cell cycle regulation, proliferation, apoptosis, differentiation, and cellular stress response. Here, we focus on how mechanical cues influence nucleolar biology. Although classical mechanotransduction is mediated by membrane-anchored signaling proteins and the cytoskeleton that propagate forces within the cell, how mechanical cues influence the organization and function of dynamically assembled, membraneless condensates remains an open question. In this review, we explore how mechanical stimuli impact the nucleolus, the most prominent nuclear condensate. We examine how extrinsic forces alter nuclear structure, thereby affecting nucleolar organization, and function. Finally, we highlight emerging evidence that positions the nucleolus as a key mediator of nuclear mechano-adaptation, linking extracellular matrix (ECM) cues, migration, confinement, and external mechanical stress to nucleolar assembly and ribosome biogenesis.