Chattaraj Aniruddha, Shakhnovich Eugene I
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
bioRxiv. 2024 Nov 25:2023.10.03.560747. doi: 10.1101/2023.10.03.560747.
Biological condensates often emerge as a multi-droplet state and never coalesce into one large droplet within the experimental timespan. Previous work revealed that the sticker-spacer architecture of biopolymers may dynamically stabilize the multi-droplet state. Here, we simulate the condensate coalescence using metadynamics approach and reveal two distinct physical mechanisms underlying the fusion of droplets. Condensates made of sticker-spacer polymers readily undergo a kinetic arrest when stickers exhibit slow exchange while fast exchanging stickers at similar levels of saturation allow merger to equilibrium states. On the other hand, condensates composed of homopolymers fuse readily until they reach a threshold density. Increase in entropy upon inter-condensate mixing of chains drives the fusion of sticker-spacer chains. We map the range of mechanisms of kinetic arrest from slow sticker exchange dynamics to density mediated in terms of energetic separation of stickers and spacers. Our predictions appear to be in qualitative agreement with recent experiments probing dynamic nature of protein-RNA condensates.
生物凝聚物通常以多液滴状态出现，并且在实验时间范围内不会聚结成一个大液滴。先前的研究表明，生物聚合物的“贴纸-间隔物”结构可能会动态稳定多液滴状态。在这里，我们使用元动力学方法模拟凝聚物聚结，并揭示了液滴融合背后的两种不同物理机制。当“贴纸”表现出缓慢交换时，由“贴纸-间隔物”聚合物制成的凝聚物很容易发生动力学停滞，而在相似饱和水平下快速交换的“贴纸”则允许合并到平衡状态。另一方面，由均聚物组成的凝聚物很容易融合，直到达到阈值密度。链间凝聚物混合时熵的增加驱动了“贴纸-间隔物”链的融合。我们绘制了从缓慢的“贴纸”交换动力学到由“贴纸”和“间隔物”的能量分离介导的密度的动力学停滞机制范围。我们的预测似乎与最近探测蛋白质-RNA凝聚物动态性质的实验定性一致。
