TY  - JOUR
AU  - Wang, Huan
AU  - Hoffmann, Christian
AU  - Tromm, Johannes V
AU  - Su, Xiao
AU  - Elliott, Jordan
AU  - Wang, Han
AU  - Deng, Mengying
AU  - McClenaghan, Conor
AU  - Baum, Jean
AU  - Pang, Zhiping P
AU  - Milovanovic, Dragomir
AU  - Shi, Zheng
TI  - Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein.
JO  - Science advances
VL  - 11
IS  - 16
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DZNE-2025-00540
SP  - eads7627
PY  - 2025
AB  - 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.
KW  - alpha-Synuclein: metabolism
KW  - alpha-Synuclein: chemistry
KW  - Viscosity
KW  - Humans
KW  - Synapsins: metabolism
KW  - Synapsins: chemistry
KW  - Elasticity
KW  - Animals
KW  - Biomolecular Condensates: metabolism
KW  - Biomolecular Condensates: chemistry
KW  - Patch-Clamp Techniques
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Synapsins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40249817
C2  - pmc:PMC12007584
DO  - DOI:10.1126/sciadv.ads7627
UR  - https://pub.dzne.de/record/278034
ER  -