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由蛋白质链动力学产生的生物分子凝聚物的中尺度特性。

Mesoscale properties of biomolecular condensates emerging from protein chain dynamics.

作者信息

Galvanetto Nicola, Ivanović Miloš T, Del Grosso Simone A, Chowdhury Aritra, Sottini Andrea, Nettels Daniel, Best Robert B, Schuler Benjamin

机构信息

Department of Biochemistry, University of Zurich, Zurich, Switzerland.

Department of Physics, University of Zurich, Zurich, Switzerland.

出版信息

ArXiv. 2025 Jan 8:arXiv:2407.19202v2.

Abstract

Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell - functions that are inherently connected to their physical properties. A remarkable aspect of such condensates is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here we investigate a series of condensates formed by complex coacervation that span about two orders of magnitude in molecular dynamics, diffusivity, and viscosity. We find that the nanoscale chain dynamics on the nano- to microsecond timescale can be accurately related to both translational diffusion and mesoscale condensate viscosity by analytical relations from polymer physics. Atomistic simulations reveal that the observed differences in friction - a key quantity underlying these relations - are caused by differences in inter-residue contact lifetimes, leading to the vastly different dynamics among the condensates. The rapid exchange of inter-residue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.

摘要

生物分子凝聚物通过生物聚合物的相分离形成,在细胞中具有重要功能,这些功能与它们的物理性质有着内在联系。此类凝聚物的一个显著特点是其粘弹性性质可在几个数量级范围内变化,但这些显著差异如何源于分子水平的纳米尺度动力学仍不清楚。在这里,我们研究了一系列通过复凝聚形成的凝聚物,它们在分子动力学、扩散率和粘度方面跨越了大约两个数量级。我们发现,通过聚合物物理学的解析关系,纳秒到微秒时间尺度上的纳米尺度链动力学可以与平动扩散和中尺度凝聚物粘度精确相关。原子模拟表明,观察到的摩擦力差异(这些关系的一个关键量)是由残基间接触寿命的差异引起的,导致了凝聚物之间截然不同的动力学。我们观察到的残基间接触的快速交换可能是防止在诸如细胞核等充满聚电解质的隔室中发生动态停滞的一种普遍机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d748/12281914/8d0dde4680de/nihpp-2407.19202v4-f0001.jpg

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