Search for: All records

Nucleocytoplasmic transport is essential for cellular function, presenting a canonical example of rapid molecular sorting inside cells. It consists of a coordinated interplay between import/export of molecules in/out the cell nucleus. Here, we investigate the role of spatiotemporal dynamics of the nucleocytoplasmic transport and its regulation. We develop a biophysical model that captures the main features of the nucleocytoplasmic transport, in particular, its regulation through the Ran cycle. Our model yields steady-state profiles for the molecular components of the Ran cycle, their relaxation times, as well as the nuclear-to-cytoplasmic molecule ratio. We show that these quantities are affected by their spatial dynamics and heterogeneity within the nucleus. Specifically, we find that the spatial nonuniformity of Ran guanine exchange factor (RanGEF)—particularly its proximity to the nuclear envelope—increases the Ran content in the nucleus. We further show that RanGEF's accumulation near the nuclear envelope results from its intrinsic dynamics as a nuclear cargo, transported by the Ran cycle itself. Overall, our work highlights the critical role of molecular spatial dynamics in cellular processes and proposes new avenues for theoretical and experimental inquiries into the nucleocytoplasmic transport. Published by the American Physical Society2024 

Chromatin – the functional form of DNA in the cell – exists in the form of a polymer immersed in a nucleoplasmic fluid inside the cell nucleus. Both chromatin and nucleoplasm are subject to active forces resulting from local biological processes. This activity leads to non-equilibrium phenomena, affecting chromatin organization and dynamics, yet the underlying physics is far from understood. Here, we expand upon a previously developed two-fluid model of chromatin and nucleoplasm by considering three types of activity in the form of force dipoles – two with both forces of the dipole acting on the same fluid (either polymer or nucleoplasm) and a third, with two forces pushing chromatin and solvent in opposite directions. We find that this latter type results in the most significant flows, dominating over most length scales of interest. Due to the friction between the fluids and their viscosity, we observe emergent screening length scales in the active flows of this system. We predict that the presence of different activity types and their relative strengths can be inferred from observing the power spectra of hydrodynamic fluctuations in the chromatin and the nucleoplasm. 

Material properties of the genome are critical for proper cellular function – they directly affect timescales and length scales of DNA transactions such as transcription, replication and DNA repair, which in turn impact all cellular processes via the central dogma of molecular biology. Hence, elucidating the genome's rheology in vivo may help reveal physical principles underlying the genome's organization and function. Here, we present a novel noninvasive approach to study the genome's rheology and its response to mechanical stress in form of nuclear injection in live human cells. Specifically, we use Displacement Correlation Spectroscopy to map nucleus-wide genomic motions pre/post injection, during which we deposit rheological probes inside the cell nucleus. While the genomic motions inform on the bulk rheology of the genome pre/post injection, the probe's motion informs on the local rheology of its surroundings. Our results reveal that mechanical stress of injection leads to local as well as nucleus-wide changes in the genome's compaction, dynamics and rheology. We find that the genome pre-injection exhibits subdiffusive motions, which are coherent over several micrometers. In contrast, genomic motions post-injection become faster and uncorrelated, moreover, the genome becomes less compact and more viscous across the entire nucleus. In addition, we use the injected particles as rheological probes and find the genome to condense locally around them, mounting a local elastic response. Taken together, our results show that mechanical stress alters both dynamics and material properties of the genome. These changes are consistent with those observed upon DNA damage, suggesting that the genome experiences similar effects during the injection process.