Fig. 3: Small molecule metabolites can decouple phase separation and fibril formation in a chemistry-specific manner.

a Effect of naturally occurring small molecule metabolites, chaotropic compounds, and small molecule modulators of protein-protein interactions on phase separation and fibrillization of SynTag-Tau. The chemical structure of the respective small molecule is also shown. b Dose-dependent effect of L-Arg in inhibition of SynTag-Tau condensate-to-amyloid transition. c SynTag-Tau partition coefficient analysis at different L-Arg doses. The thick dashed line of the violin plot represents the median based on data of 53 condensates from three independent replicates, whereas the thinner dotted lines above and below represent the upper and lower quartiles, respectively. d (top) Chemical structure of α-dansyl-L-arginine (dansyl-L-Arg). (bottom) Partitioning of either dansyl chloride (dansyl-Cl) or dansyl-L-Arg doped along with L-Arg in SynTag-Tau condensates, visualized using Alexa594- (A594) labeled SynTag-Tau, at 2 h sample age. e Partition coefficient analysis of either dansyl-Cl or dansyl-L-Arg, either with or without L-Arg in SynTag-Tau condensates. The thick dashed line of the violin plot represents the median based on data of 32 condensates from three independent replicates, whereas the thinner dotted lines above and below represent the upper and lower quartiles, respectively. f L-Arg ethyl ester (L-Arg EE), a derivative of L-Arg that lacks a carboxyl group, failed to prevent condensate aging to fibrils. D-Arginine (D-Arg) treated condensates do not transition to fibrils, similar to the L-Arg condition shown in (a). The display range of images shown across these figure panels was adjusted independently for better clarity. Each of these experiments was independently repeated three times. Source data are provided as a Source Data file.