The rich inner life of the cell nucleus: dynamic organization, active flows, and emergent rheology.

The cell nucleus stores the genetic material essential for life, and provides the environment for transcription, maintenance, and replication of the genome. Moreover, the nucleoplasm is filled with subnuclear bodies such as nucleoli that are responsible for other vital functions. Overall, the nucleus presents a highly heterogeneous and dynamic environment with diverse functionality. Here, we propose that its biophysical complexity can be organized around three inter-related and interactive facets: heterogeneity, activity, and rheology. Most nuclear constituents are sites of active, ATP-dependent processes and are thus inherently dynamic: The genome undergoes constant rearrangement, the nuclear envelope flickers and fluctuates, nucleoli migrate and coalesce, and many of these events are mediated by nucleoplasmic flows and interactions. And yet there is spatiotemporal organization in terms of hierarchical structure of the genome, its coherently moving regions and membrane-less compartmentalization via phase-separated nucleoplasmic constituents. Moreover, the non-equilibrium or activity-driven nature of the nucleus gives rise to emergent rheology and material properties that impact all cellular processes via the central dogma of molecular biology. New biophysical insights into the cell nucleus can come from appreciating this rich inner life.