ArticleProceedings of the National Academy of Sciences of the United States of America2020
Liquid-liquid phase separation of type II diabetes-associated IAPP initiates hydrogelation and aggregation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The predictive accuracy of machine learning for the risk of death in HIV patients: a systematic review and meta-analysis.BMC infectious diseases · 2024Pooled it
- Deletion Analysis of Phase Separation, Amyloid Formation and Prion Propagation by the Intrinsically Disordered Region of Yeast Sup35 Protein.International journal of molecular sciences · 2026Article
- QBP1 Peptide as a Potential Anti-Amyloidogenic Therapy for Type 2 Diabetes: An In Vitro Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Effect of Protein Tagging on Aggregation and Phase Separation.Journal of cellular biochemistry · 2026Review
- A global thermodynamic-kinetic model capturing the hallmarks of liquid-liquid phase separation and amyloid aggregation.Cell reports. Physical science · 2026Article
- A Systematic Evaluation of Protein Phase Separation Predictors across Diverse Protein Landscapes.Computational and structural biotechnology journal · 2026Article
- APOE Genotype Difference in the Biphasic Modulation of Amyloid-β Aggregation by Direct Binding and Lowering the Nucleation Barrier.Biomacromolecules · 2025Article
- Liquid-liquid phase separation-related genes in the immune microenvironment and diagnosis of focal segmental glomerulosclerosis and minimal change disease.Renal failure · 2025Article
- Review
- Emerging biophysical origins and pathogenic implications of amyloid oligomers.Nature communications · 2025Review
- Review
- TDP43 and huntingtin Exon-1 undergo a conformationally specific interaction that strongly alters the fibril formation of both proteins.The Journal of biological chemistry · 2024Article
- Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Understanding and fine tuning the propensity of ATP-driven liquid-liquid phase separation with oligolysine.Physical chemistry chemical physics : PCCP · 2024Article
- Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.bioRxiv : the preprint server for biology · 2024Article
- Fluorescent protein tagging promotes phase separation and alters the aggregation pathway of huntingtin exon-1.The Journal of biological chemistry · 2024Article
- Liquid-Liquid Phase Separation and Protective Protein Aggregates in Bacteria.Molecules (Basel, Switzerland) · 2023Review
- Location and Concentration of Aromatic-Rich Segments Dictates the Percolating Inter-Molecular Network and Viscoelastic Properties of Ageing Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Amyloid Aggregation and Liquid-Liquid Phase Separation from the Perspective of Phase Transitions.The journal of physical chemistry. B · 2023Review
- Modulating Nanodroplet Formation En Route to Fibrillization of Amyloid Peptides with Designed Flanking Sequences.Biomacromolecules · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloidoses (misfolded polypeptide accumulation) are among the most debilitating diseases our aging societies face. Amyloidogenesis can be catalyzed by hydrophobic-hydrophilic interfaces (e.g., air-water interface in vitro [AWI]). We recently demonstrated hydrogelation of the amyloidogenic type II diabetes-associated islet amyloid polypeptide (IAPP), a hydrophobic-hydrophilic interface-dependent process with complex kinetics. We demonstrate that human IAPP undergoes AWI-catalyzed liquid-liquid phase separation (LLPS), which initiates hydrogelation and aggregation. Insulin modulates these processes but does not prevent them. Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrogelation and aggregation do. Interestingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology. By developing an experimental setup and analysis tools, we show that, within the whole system (beyond the droplet stage), macroscopic interconnected aggregate clusters form, grow, fuse, and evolve via internal rearrangement, leading to overall hydrogelation. As the AWI-adsorbed gelled layer matures, its microviscosity increases. LLPS-driven aggregation may be a common amyloid feature and integral to pathology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.