The responsive nucleus: morphological signatures of cellular state

Nuclear morphology is increasingly recognized as an integrative indicator of cellular state across diverse physiological and pathological conditions. Beyond storing genetic material, the nucleus also acts as a dynamic sensor responding to mechanical, biochemical, and epigenetic cues. These stimuli reshape nuclear size, architecture, chromatin organization, and envelope integrity providing valuable information about cell cycle progression, differentiation, senescence, and stress responses. Such features offer a scalable and non-invasive approach to assess cell fate. In this review, we position the nuclear envelope as a key sensor of nuclear morphology, outline major triggers of nuclear deformation, discuss the molecular and biophysical processes preserving nuclear integrity and highlight the diversity of nuclear phenotypes with diagnostic and prognostic value. This review provides a comprehensive and critical synthesis of the current knowledge on the regulation and functional relevance of nuclear morphology to serve as a resource and reference point for future interdisciplinary studies.