Determinants for Fusion Speed of Biomolecular Droplets.

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.