Mechanical stress affects dynamics and rheology of the human genome
Mechanical stress affects dynamics and rheology of the human genome
复制标题
机械应力影响人类基因组的动力学和流变学
DOI：
10.1039/d1sm00983d
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发表时间：
2021
期刊：
影响因子：
3.4
通讯作者：
Zidovska, Alexandra
中科院分区：
文献类型：
--
作者：
Caragine, Christina M.;Kanellakopoulos, Nikitas;Zidovska, Alexandra
基因组的物质特性对于正常的细胞功能至关重要-它们直接影响DNA事务的时间尺度和长度尺度，例如转录，复制和DNA修复，这反过来又通过中心法则影响所有细胞过程。因此，阐明基因组在体内的流变学可能有助于揭示基因组组织和功能的物理原理。在这里，我们提出了一种新的非侵入性的方法来研究基因组的流变学及其对核注射形式的机械应力的反应。具体来说，我们使用位移相关光谱（DCS）[1]来绘制注射前/后的全核基因组运动，在此期间我们将存款流变探针沉积在细胞核内。虽然前者告知基因组的核范围的整体流变学，后者告知探针周围环境的局部流变学。我们的基因组的动力学和流变学的空间分辨映射显示，注射的机械应力导致基因组的压实，动力学和流变学的局部以及核范围的变化。总之，我们的研究结果表明，机械应力可以影响基因组的动力学和材料特性。这项研究得到了美国国家科学基金会赠款CAREER PHY-1554880、CMMI-1762506和纽约大学MRSEC DMR-1420073的支持。
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. 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 the form of nuclear injection. Specifically, we use Displacement Correlation Spectroscopy (DCS)[1] to map nucleus-wide genomic motions pre/post injection, during which we deposit rheological probes inside the nucleus. While the former informs on the nucleus-wide bulk rheology of the genome, the latter informs on the local rheology of the probe's surroundings. Our spatially-resolved mapping of the genome’s dynamics and rheology reveals that mechanical stress of injection leads to local as well as nucleus-wide changes in the genome's compaction, dynamics and rheology. Taken together, our results show that mechanical stress can affect both dynamics and material properties of the genome. This research was supported by the National Science Foundation Grants CAREER PHY-1554880, CMMI-1762506 and NYU MRSEC DMR-1420073.