engWang, HuanHoffmann, ChristianMilovanovic, DragomirShi, ZhengTromm, Johannes VSu, XiaoElliott, JordanWang, HanDeng, MengyingMcClenaghan, ConorBaum, JeanPang, Zhiping PLive-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein.info:eu-repo/classification/ddc/500alpha-Synuclein: metabolismalpha-Synuclein: chemistryViscosityHumansSynapsins: metabolismSynapsins: chemistryElasticityAnimalsBiomolecular Condensates: metabolismBiomolecular Condensates: chemistryPatch-Clamp Techniquesalpha-SynucleinSynapsinsSynapsin 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.Science advances 11(16), eads7627 (2025). doi:10.1126/sciadv.ads7627info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAssoc.2025info:eu-repo/semantics/openAccessDEhttps://pub.dzne.de/record/278034https://pub.dzne.de/search?p=id:%22DZNE-2025-00540%22Researchersinfo:eu-repo/semantics/altIdentifier/pmid/pmid:40249817info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.ads7627info:eu-repo/semantics/altIdentifier/issn/2375-2548