Language
English
Publication Date
3-25-2026
Journal
Biomolecules
DOI
10.3390/biom16040492
PMID
42072614
PMCID
PMC13113973
PubMedCentral® Posted Date
3-25-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Neurodegenerative diseases feature diverse pathological protein aggregates, including Lewy bodies in Alzheimer's disease (AD) and skein-like filaments in amyotrophic lateral sclerosis (ALS). The physical mechanisms underlying this morphological diversity remain unclear. Here, we demonstrate that aggregation of the prion-like domain of hnRNPA1 (A1PrD), implicated in AD and ALS, is driven by solution composition and phase transition dynamics. Utilizing 3D timelapse and fluorescence lifetime imaging microscopy, we show that solution conditions modulate phase separation, gelation, and fibrillation, resulting in distinct structures such as fibril, gel, and starburst morphologies. Homotypic and heterotypic interactions between A1PrD and RNA were observed to shift the balance between pathological and physiological condensates. Importantly, amyloid-rich starbursts displayed prion-like infection capabilities toward amyloid-poor condensates. Our findings highlight how the interplay between solution composition and kinetic balances of liquid-liquid phase separation, gelation, and fibrillation shapes the diverse pathological aggregate morphologies characteristic of neurodegenerative diseases.
Keywords
Humans, Heterogeneous Nuclear Ribonucleoprotein A1, Phase Separation, Biomolecular Condensates, Protein Aggregates, Amyloid, Alzheimer Disease, Amyotrophic Lateral Sclerosis, Prions, Protein Domains, Protein Aggregation, Pathological, hnRNPA1, prion-like domain, LLPS, biomolecular condensates, aggregation, fibrillation, phase transitions, Alzheimer’s disease, ALS, FLIM
Published Open-Access
yes
Recommended Citation
Ferreon, Josephine C; Choi, Kyoung-Jae; Quan, My Diem; et al., "Modulation of Biomolecular Aggregate Morphology and Condensate Infectivity." (2026). Faculty, Staff and Students Publications. 8033.
https://digitalcommons.library.tmc.edu/baylor_docs/8033