A Global Thermodynamic-Kinetic Model Capturing the Hallmarks of Liquid-Liquid Phase Separation and Amyloid Aggregation.

ABSTRACT: Aberrant aggregation of proteins into amyloid fibrils is associated with numerous neurodegenerative, systemic and metabolic diseases. Amyloidogenic proteins undergo spontaneous liquid-liquid phase separation (LLPS), rapidly forming protein-rich condensates prior to fibrillization. However, the exact effects of LLPS on amyloid aggregation remain unclear as contrasting fibrillization-promotion, inhibition and even biphasic effects have been reported in the literature. In this study, we integrate LLPS-induced heterogeneity of protein concentrations into a thermodynamic-kinetic model of amyloid aggregation. We adopt the phase transition theory and introduce protein condensates as an additional protein state alongside non-interacting monomers, oligomers and fibrils. Oligomerization and fibrilli

SUBMITTER: Bhandari K 

PROVIDER: S-EPMC12154704 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature