Structural reorganization and relaxation dynamics of axially stressed chromosomes
Structural reorganization and relaxation dynamics of axially stressed chromosomes
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轴向应力染色体的结构重组和松弛动力学
DOI：
10.1016/j.bpj.2023.03.029
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发表时间：
2023
影响因子：
3.4
通讯作者：
Onuchic, José N.
中科院分区：
文献类型：
--
作者：
Ruben, Benjamin S.;Brahmachari, Sumitabha;Contessoto, Vinícius G.;Cheng, Ryan R.;Oliveira Junior, Antonio B.;Di Pierro, Michele;Onuchic, José N.
染色体在整个细胞周期中承受机械应力;例如，由有丝分裂期间纺锤体纤维拉动染色体或细胞迁移期间细胞核变形引起。生理应激反应与染色体结构和功能密切相关。有丝分裂染色体的微观力学研究揭示了它们是非常可扩展的对象，并为有丝分裂染色体组织的早期模型提供了信息。我们使用数据驱动的粗粒度聚合物建模方法来探索单个染色体的空间组织与其新兴的机械性能之间的关系。特别是，我们调查我们的模型染色体的机械性能轴向拉伸。模拟拉伸导致小应变的线性力-延伸曲线，有丝分裂染色体的行为比间期染色体硬约10倍。研究它们的弛豫动力学，我们发现染色体是粘弹性固体，在有丝分裂中变成固体状的相间具有高度液体状的粘性行为。这种新兴的机械刚度源于纵向压缩，一个有效的潜在捕获环挤压SMC复合物的活性。染色体在大应变下通过解开而变性，其特征在于大规模折叠模式的打开。通过量化机械扰动对染色体结构特征的影响，我们的模型提供了对染色体体内力学的细致入微的理解。
Chromosomes endure mechanical stresses throughout the cell cycle; for example, resulting from the pulling of chromosomes by spindle fibers during mitosis or deformation of the nucleus during cell migration. The response to physical stress is closely related to chromosome structure and function. Micromechanical studies of mitotic chromosomes have revealed them to be remarkably extensible objects and informed early models of mitotic chromosome organization. We use a data-driven, coarse-grained polymer modeling approach to explore the relationship between the spatial organization of individual chromosomes and their emergent mechanical properties. In particular, we investigate the mechanical properties of our model chromosomes by axially stretching them. Simulated stretching led to a linear force-extension curve for small strain, with mitotic chromosomes behaving about 10-fold stiffer than interphase chromosomes. Studying their relaxation dynamics, we found that chromosomes are viscoelastic solids with a highly liquid-like, viscous behavior in interphase that becomes solid-like in mitosis. This emergent mechanical stiffness originates from lengthwise compaction, an effective potential capturing the activity of loop-extruding SMC complexes. Chromosomes denature under large strains via unraveling, which is characterized by opening of large-scale folding patterns. By quantifying the effect of mechanical perturbations on the chromosome's structural features, our model provides a nuanced understanding of in vivo mechanics of chromosomes.