Differential Effects of α-Synuclein Monomers and Seeds on the Material Properties of Tau Condensates
In the authors' words
Abstract Tau and α-Synuclein (αSyn) frequently coaggregate in various neurodegenerative disorders. Recently, Tau has been shown to form dynamic, liquid-like condensates that can recruit αSyn, and potentially serve as a precursor to pathological crosstalk and aggregation. However, the quantitative impact of αSyn on the material properties of these condensates remains elusive. Here, we measure the viscosity and interfacial tension of Tau condensates and determine how these properties are modulated by αSyn monomers and fibril seeds. We find that while both forms of αSyn partition efficiently into Tau condensates, they exert vastly different effects on the condensate’s material state. The viscosity of Tau condensates remains unchanged in the presence of αSyn monomers at concentrations up to 200 μM, accompanied by a moderate reduction in the condensates’ interfacial tension. In contrast, adding just 5 μM αSyn fibril seeds triggers rapid maturation of Tau condensates, manifested by a nearly 100-fold increase in their steady-state viscosity within 1 h. These findings provide quantitative insights into condensate mechanics, highlighting the unique capacity of αSyn seeds to modulate Tau condensate viscosity, which may underlie the formation of pathological aggregates.
Appeared: Friday, September 25. Journal of the American Chemical Society. Peer-reviewed journal.
DOI: 10.1021/jacs.6c07726