小柯机器人

研究绘制生物分子凝聚物的成核图谱
2021-09-24 14:27

美国普林斯顿大学Clifford P. Brangwynne研究团队绘制出生物分子凝聚物的成核图谱。这一研究成果于2021年9月22日在线发表在国际学术期刊《自然》上。

研究人员表示,活细胞内的所有结构必须在正确的时间和地点形成。这包括凝聚物,如核仁、卡哈尔体和应激颗粒,它们通过生物大分子的液-液相分离形成,特别是富含内在无序区(IDRs)的蛋白质。在非生物系统中,当热波动克服了表面张力造成的能量障碍时,就会出现有核相分离的初始阶段。这种现象可以用经典成核理论(CNT)来模拟,它描述了液滴成核的速度如何取决于过饱和度,而液滴出现的位置则由界面异质性控制。然而,由于细胞内环境的多成分和高度复杂的性质,包括不同的IDR的存在,其生物分子相互作用的特异性尚不清楚,这一框架是否适用于活细胞仍然是未知的。

研究人员表明,尽管有这种复杂性,活细胞中的成核过程与无生命物质中的成核过程相似,但成核点的功效可以通过其生物分子特征进行调整。通过定量描述活细胞中内源性和仿生物凝聚物的成核动力学,研究人员发现凝聚物成核的关键特征可以通过一个类似CNT的理论框架来定量理解。成核率可以通过兼容的生物分子(IDR)种子得到大幅提高,而细胞过程的动力学可以影响凝聚物成核率和位置的特异性。这个定量框架揭示了细胞内成核的情况,并为工程合成凝聚物在空间和时间上的精确定位铺平了道路。

附:英文原文

Title: Nucleation landscape of biomolecular condensates

Author: Shimobayashi, Shunsuke F., Ronceray, Pierre, Sanders, David W., Haataja, Mikko P., Brangwynne, Clifford P.

Issue&Volume: 2021-09-22

Abstract: All structures within living cells must form at the right time and place. This includes condensates such as the nucleolus, Cajal bodies and stress granules, which form via liquid–liquid phase separation of biomolecules, particularly proteins enriched in intrinsically disordered regions (IDRs)1,2. In non-living systems, the initial stages of nucleated phase separation arise when thermal fluctuations overcome an energy barrier due to surface tension. This phenomenon can be modelled by classical nucleation theory (CNT), which describes how the rate of droplet nucleation depends on the degree of supersaturation, whereas the location at which droplets appear is controlled by interfacial heterogeneities3,4. However, it remains unknown whether this framework applies in living cells, owing to the multicomponent and highly complex nature of the intracellular environment, including the presence of diverse IDRs, whose specificity of biomolecular interactions is unclear5,6,7,8. Here we show that despite this complexity, nucleation in living cells occurs through a physical process similar to that in inanimate materials, but the efficacy of nucleation sites can be tuned by their biomolecular features. By quantitatively characterizing the nucleation kinetics of endogenous and biomimetic condensates in living cells, we find that key features of condensate nucleation can be quantitatively understood through a CNT-like theoretical framework. Nucleation rates can be substantially enhanced by compatible biomolecular (IDR) seeds, and the kinetics of cellular processes can impact condensate nucleation rates and specificity of location. This quantitative framework sheds light on the intracellular nucleation landscape, and paves the way for engineering synthetic condensates precisely positioned in space and time.

DOI: 10.1038/s41586-021-03905-5

Source: https://www.nature.com/articles/s41586-021-03905-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0