Fusion Speed of Biomolecular Condensates

Biomolecular condensates 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 condensates 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 condensates. 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 portends a unified understanding of the underlying physicochemical determinants. Entry for the Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=46 SRC="FIGDIR/small/164897v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@e9fb56org.highwire.dtl.DTLVardef@17402f6org.highwire.dtl.DTLVardef@16ea0b8org.highwire.dtl.DTLVardef@1f999ff_HPS_FORMAT_FIGEXP M_FIG The tendency of biomolecular condensates to fuse is key to cellular function and diseases. Using optical tweezers, fluorescence microscopy, and theoretical modeling, Ghosh and Zhou have begun to unravel the molecular origin for disparate fusion speeds among different biomolecular condensates. They found that fusion speed is dictated by macromolecular packing density inside condensates, which can be reported by ThT fluorescence. C_FIG