Year: 2018
Type: article
Abstract: 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.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: National Science Foundation, York University, National Institutes of Health, Directorate for Biological Sciences, Materials Research Science and Engineering Center, Harvard University, National Institute of General Medical Sciences, Division of Materials Research, Division of Civil, Mechanical and Manufacturing Innovation
Awards: Collaborative Research: FRG: Understanding and Controlling Active Fluids through Modeling, Simulation, and Experiment, G1297368160, G1410324694, G1472743852, G154586550, G2199371856, Collaborative Research: Interphase Chromatin as a Complex Active Fluid: Experiments and Microscopic to Mesoscopic Modeling, G3387330441, Collaborative Research: Multiscale Study of Active Cellular Matter: Simulation, Modeling, and Analysis, Collaborative Research: FRG: Understanding and Controlling Active Fluids through Modeling, Simulation, and Experiment, G455972330, G6434721332, NYU Materials Research Science and Engineering Center, G6671297155, CAREER: Physics of Chromatin: Micromechanics of Active Chromatin Dynamics in Interphase, Mechanism and Function of Chromatin Positional Dynamics in Interphase, G7805964360, G821361635, Collaborative Research: Interphase Chromatin as a Complex Active Fluid: Experiments and Microscopic to Mesoscopic Modeling
OpenAlex ID: W2951131740