Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Department of Physics, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Angew Chem Int Ed Engl. 2020 Nov 16;59(47):20837-20840. doi: 10.1002/anie.202006711. Epub 2020 Sep 8.
Biomolecular droplets formed through phase separation have a tendency to fuse. The speed with which fusion occurs is a direct indicator of condensate liquidity, which is key to both cellular functions and diseases. Using a dual-trap optical tweezers setup, we found the fusion speeds of four types of droplets to differ by two orders of magnitude. The order of fusion speed correlates with the fluorescence of thioflavin T, which in turn reflects the macromolecular packing density inside droplets. Unstructured protein or polymer chains pack loosely and readily rearrange, leading to fast fusion. In contrast, structured protein domains pack more closely and have to break extensive contacts before rearrangement, corresponding to slower fusion. This molecular interpretation for disparate fusion speeds provides mechanistic insight into the assembly and aging of biomolecular droplets.
生物分子液滴通过相分离形成，具有融合的趋势。融合发生的速度是凝聚态液体性的直接指标，这对细胞功能和疾病都至关重要。我们使用双阱光镊装置发现，四种类型的液滴的融合速度相差两个数量级。融合速度的顺序与硫黄素 T 的荧光强度相关，而荧光强度又反映了液滴内部的高分子堆积密度。无规的蛋白质或聚合物链松散堆积，容易重新排列，导致快速融合。相比之下，结构蛋白结构域的堆积更紧密，在重新排列之前必须打破广泛的接触，这对应着较慢的融合。这种对不同融合速度的分子解释为生物分子液滴的组装和老化提供了机制上的见解。
