Biophysical Society Thematic Meeting | Tutzing 2026

Single-Molecule FRET: The Next 30 Years

Poster Abstracts

53-POS Board 27 MAPPING THE STRUCTURAL FEATURES OF FUS: FROM ISOLATED MOLECULES OVER OLIGOMERS TO PHASE-SEPARATED CONDENSATES Laura T Vogel 1 ; Archita Sarkar 1 ; Titus M Franzmann 2 ; Oleg Opanasyuk 1 ; Suren Felekyan 1 ; Jan-Hendrik Budde 1 ; Tim Loibl 1 ; Lize-Mari van der Linden 2 ; Nagaraja Chappidi 2 ; Giacomo Bartolucci 3 ; Christoph A Weber 3 ; Ralf Kühnemuth 1 ; Simon Alberti 2 ; Claus Seidel 1 ; 1 Heinrich-Heine University, Düsseldorf, Chair for Molecular Physical Chemistry, Düsseldorf, Germany 2 Technical University Dresden, Biotechnology Center, Center for Molecular and Cellular Bioengineering, Dresden, Germany 3 Augsburg University, Chair for Theoretical Physics, Augsburg, Germany The Intrinsically Disordered Protein (IDP), FUS (Fused in Sarcoma), forms biomolecular condensates that are directly linked to neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Despite their biological significance, the conformational properties of individual FUS molecules remain poorly understood due to their structural heterogeneity, environmental sensitivity, and in-chain complex dynamics. Using biophysical techniques such as Multiparameter Fluorescence Detection (MFD), we map the pathway from flexible FUS monomers to nanoclusters and fibrillar assemblies. Our findings indicate that pFCS detects a salt-dependent expansion of isolated FUS molecules and a structural relaxation timescale of 200–400 µs. Analyses of various FUS fragments and variants have helped elucidate the compactness of the native-length FUS protein by deciphering the intra- and intermolecular interactions that underlie its packing. smFRET and eTCSPC data reveal a quasi-continuum of relaxation times of FUS, underscoring that IDPs are not random coils but dynamic ensembles. Below the saturation concentration (C sat ), FUS forms reversible oligomers and clusters that compact, align, and grow autocatalytically—processes suppressed by RNA. Above C sat , FUS assembles into condensates featuring nanometer-scale meshwork that progressively matures into heterogeneous droplets and fibrils. These findings map a quantitative framework for IDP assembly and prioritize early metastable states for intervention 1-4 .

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