Small Molecules Modulate Liquid‐to‐Solid Transitions in Phase‐Separated Tau Condensates

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Abstract: In Tau protein condensates formed by the Liquid–Liquid Phase Separation (LLPS) process, liquid‐to‐solid transitions lead to the formation of fibrils implicated in Alzheimer's disease. Here, by tracking two contacting Tau‐rich droplets using a simple and nonintrusive video microscopy, we found that the halftime of the liquid‐to‐solid transition in the Tau condensate is affected by the Hofmeister series according to the solvation energy of anions. After dissecting functional groups of physiologically relevant small molecules using a multivariate approach, we found that charged groups facilitate the liquid‐to‐solid transition in a manner similar to the Hofmeister effect, whereas hydrophobic alkyl chains and aromatic rings inhibit the transition. Our results not only elucidate the driving force of the liquid‐to‐solid transition in Tau condensates, but also provide guidelines to design small molecules to modulate this important transition for many biological functions for the first time.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Small Molecules Modulate Liquid‐to‐Solid Transitions in Phase‐Separated Tau Condensates ; day:05 ; month:04 ; year:2022 ; extent:1
Angewandte Chemie ; (05.04.2022) (gesamt 1)

Creator: Jonchhe, Sagun
Pan, Wei
Pokhrel, Pravin
Mao, Hanbin

DOI: 10.1002/ange.202113156

URN: urn:nbn:de:101:1-2022040615090329790948

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:30 AM CEST

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Jonchhe, Sagun
Pan, Wei
Pokhrel, Pravin
Mao, Hanbin

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