17 Wang, Huan Hoffmann, Christian Tromm, Johannes V Su, Xiao Elliott, Jordan Wang, Han Deng, Mengying McClenaghan, Conor Baum, Jean Pang, Zhiping P Milovanovic, Dragomir Shi, Zheng AG Milovanovic (Berlin) AG Milovanovic (Bonn) Science advances Science advances Assoc. Washington, DC [u.a.] 2375-2548 10.1126/sciadv.ads7627 English eads7627 16 11 Synapsin and α-synuclein represent a growing list of condensate-forming proteins where the material states of condensates are directly linked to cellular functions (e.g., neurotransmission) and pathology (e.g., neurodegeneration). However, quantifying condensate material properties in living systems has been a substantial challenge. Here, we develop micropipette aspiration and whole-cell patch-clamp (MAPAC), a platform that allows direct material quantification of condensates in live cells. We find 10,000-fold variations in the viscoelasticity of synapsin condensates, regulated by the partitioning of α-synuclein, a marker for synucleinopathies. Through in vitro reconstitutions, we identify multiple molecular factors that distinctly regulate the viscosity, interfacial tension, and maturation of synapsin condensates, confirming the cellular roles of α-synuclein. Overall, our study provides unprecedented quantitative insights into the material properties of neuronal condensates and reveals a crucial role of α-synuclein in regulating condensate viscoelasticity. Furthermore, we envision MAPAC applicable to study a broad range of condensates in vivo. PUB:(DE-HGF)16, ; 0, ; alpha-Synuclein: metabolism alpha-Synuclein: chemistry Viscosity Humans Synapsins: metabolism Synapsins: chemistry Elasticity Animals Biomolecular Condensates: metabolism Biomolecular Condensates: chemistry Patch-Clamp Techniques alpha-Synuclein Synapsins Journal Article 2025 DZNE-2025-00540 2025 pmc:PMC12007584 pmid:40249817 https://pub.dzne.de/record/278034 https://doi.org/10.1126/sciadv.ads7627