Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA 92093;
Center for Computational Biology, Flatiron Institute, New York, NY 10010.
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11442-11447. doi: 10.1073/pnas.1807073115. Epub 2018 Oct 22.
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.
人类基因组在细胞内的三维时空组织仍然是细胞生物学中的一个主要开放性问题。在两次细胞分裂之间的时间里,染色质——细胞中 DNA 的功能形式——以未浓缩的聚合形式充满细胞核。最近的体内成像实验揭示了染色质的相干运动,其位移具有长达数微米的长程相关性,并持续数秒。为了阐明这些运动背后的机制,我们开发了一种粗粒化的活性聚合物模型,其中染色质被表示为受到分子马达作用的受限柔性链,这些分子马达通过对系统施加偶极力来驱动流体流动。该模型的数值模拟考虑了位阻和流体力学相互作用以及内部链力学。这些结果表明,在涉及伸展偶极子的系统中会出现相干运动,同时伴随着大规模的链重排和向列有序。与实验的比较显示出良好的定性一致性,并支持这样的假设,即染色质相关的活性马达蛋白之间自组织的长程流体力学耦合负责观察到的相干动力学。