Extensile motor activity drives coherent motions in a model of interphase chromatin

Extensile motor activity drives coherent motions in a model of interphase chromatin
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伸展运动活动驱动间期染色质模型中的连贯运动

DOI:
10.1073/pnas.1807073115
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发表时间:
2018
期刊:
Proceedings of the National Academy of Sciences
影响因子:
--
通讯作者:
Zidovska, Alexandra
Zidovska, Alexandra
中科院分区:
--
文献类型:
--
作者:
Saintillan, David;Shelley, Michael J.;Zidovska, Alexandra

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细胞核内人类基因组的 3D 时空组织仍然是细胞生物学中的一个主要悬而未决的问题。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)以其未缩合的聚合形式填充细胞核。最近的体内成像实验表明,染色质的移动是连贯的,其位移具有微米级的长程相关性,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活性聚合物模型,其中染色质被表示为受分子马达作用的有限柔性链,分子马达通过在系统上施加偶极力来驱动流体流动。该模型的数值模拟考虑了空间相互作用和流体动力学相互作用以及内链力学。这些表明相干运动出现在涉及可拉伸偶极子的系统中,并伴随着大规模的链重构和向列排序。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:染色质相关活性运动蛋白之间的自组织长程流体动力耦合是观察到的相干动力学的原因。
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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