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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.
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Extensile motor activity drives coherent motions in a model of interphase chromatin
The 3D spatiotemporal organization of the human genome inside the cell nucleus remains a major open question in cellular biology. In the time between two cell divisions, chromatin—the functional form of DNA in cells—fills the nucleus in its uncondensed polymeric form. Recent in vivo imaging experiments reveal that the chromatin moves coherently, having displacements with long-ranged correlations on the scale of micrometers and lasting for seconds. To elucidate the mechanism(s) behind these motions, we develop a coarse-grained active polymer model where chromatin is represented as a confined flexible chain acted upon by molecular motors that drive fluid flows by exerting dipolar forces on the system. Numerical simulations of this model account for steric and hydrodynamic interactions as well as internal chain mechanics. These demonstrate that coherent motions emerge in systems involving extensile dipoles and are accompanied by large-scale chain reconfigurations and nematic ordering. Comparisons with experiments show good qualitative agreement and support the hypothesis that self-organizing long-ranged hydrodynamic couplings between chromatin-associated active motor proteins are responsible for the observed coherent dynamics.
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- PAR ID:
- 10077674
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 115
- Issue:
- 45
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- p. 11442-11447
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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