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Chromatin mechanics dictates subdiffusion and coarsening dynamics of embedded condensates
Nature Physics ( IF 17.6 ) Pub Date : 2021-01-11 , DOI: 10.1038/s41567-020-01125-8
Daniel S. W. Lee , Ned S. Wingreen , Clifford P. Brangwynne

DNA is organized into chromatin, a complex polymeric material that stores information and controls gene expression. An emerging mechanism for biological organization, particularly within the crowded nucleus, is biomolecular phase separation into condensed droplets of protein and nucleic acids. However, the way in which chromatin impacts the dynamics of phase separation and condensate formation is poorly understood. Here we utilize a powerful optogenetic strategy to examine the interplay of droplet coarsening with the surrounding viscoelastic chromatin network. We demonstrate that droplet growth dynamics are directly inhibited by the chromatin-dense environment, which gives rise to an anomalously slow coarsening exponent, β ≈ 0.12, contrasting with the classical prediction of β = 1/3. Using scaling arguments and simulations, we show how this arrested growth can arise due to subdiffusion of individual condensates, predicting β ≈ α/3, where α is the diffusive exponent. Tracking the fluctuating motion of condensates within chromatin reveals a subdiffusive exponent, α ≈ 0.5, which explains the anomalous coarsening behaviour and is also consistent with Rouse-like dynamics arising from the entangled chromatin. Our findings have implications for the biophysical regulation of the size and shape of biomolecular condensates and suggest that condensate emulsions can be used to probe the viscoelastic mechanical environment within living cells.



中文翻译:

染色质力学决定了嵌入凝聚物的细分和粗化动力学

DNA 被组织成染色质,这是一种复杂的聚合材料,可存储信息并控制基因表达。一种新兴的生物组织机制,特别是在拥挤的细胞核内,是将生物分子相分离成蛋白质和核酸的凝聚液滴。然而,染色质影响相分离和冷凝物形成动力学的方式知之甚少。在这里,我们利用强大的光遗传学策略来检查液滴粗化与周围粘弹性染色质网络的相互作用。我们证明了液滴生长动力学直接受到染色质密集环境的抑制,这会导致异常缓慢的粗化指数β  ≈ 0.12,与经典的β预测相反 = 1/3。使用比例参数和模拟,我们展示了这种停滞的增长是如何由于单个冷凝物的再扩散而产生的,预测β  ≈  α /3,其中α是扩散指数。跟踪染色质内冷凝物的波动运动揭示了一个次扩散指数,α≈0.5  这解释了异常的粗化行为,并且也与纠缠染色质引起的 Rouse 样动力学一致。我们的研究结果对生物分子缩合物的大小和形状的生物物理调节具有重要意义,并表明缩合物乳液可用于探测活细胞内的粘弹性机械环境。

更新日期:2021-01-11
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