Imperial College London
Portrait Picture

DrChiu FanLee

Faculty of Engineering, Department of Bioengineering

Reader in Theoretical Biophysics
 
 
 
//

Contact

 

+44 (0)20 7594 6493c.lee Website

 
 
//

Location

 

3.17Royal School of MinesSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Pytowski:2020:10.1073/pnas.1916716117,
author = {Pytowski, L and Lee, CF and Foley, AC and Vaux, DJ and Jean, L},
doi = {10.1073/pnas.1916716117},
journal = {Proceedings of the National Academy of Sciences of USA},
pages = {12050--12061},
title = {Liquid–liquid phase separation of type II diabetes-associated IAPP initiates hydrogelation and aggregation},
url = {http://dx.doi.org/10.1073/pnas.1916716117},
volume = {117},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Pytowski,L
AU  - Lee,CF
AU  - Foley,AC
AU  - Vaux,DJ
AU  - Jean,L
DO  - 10.1073/pnas.1916716117
EP  - 12061
PY  - 2020///
SN  - 0027-8424
SP  - 12050
TI  - Liquid–liquid phase separation of type II diabetes-associated IAPP initiates hydrogelation and aggregation
T2  - Proceedings of the National Academy of Sciences of USA
UR  - http://dx.doi.org/10.1073/pnas.1916716117
UR  - https://www.pnas.org/content/117/22/12050
UR  - http://hdl.handle.net/10044/1/79144
VL  - 117
ER  -
Download