Aggregation of fibrils and plaques in amyloid molecular systems.
Amyloidlike proteins form highly organized aggregates, such as fibrils and plaques, preceded by the assembly of a wide range of unstructured oligomers and protofibrils. Despite their importance in a number of human neurodegenerative diseases, a comprehensive understanding of their kinetics and thermodynamics is still missing. We investigate, by computer simulations, a realistic model of amyloid molecules interacting via the experimentally determined Derjaguin-Landau-Verwey-Overbeek potential and derive its phase diagram. We show that fibrils and plaques, along with their precursors, correspond to different equilibrium and metastable thermodynamics phases and discuss the dynamical mechanisms leading to the nucleation and self-assembly of large scale structures.
Nicodemi
Mario
M
Department of Physics and Complexity Science Centre, University of Warwick, Coventry, United Kingdom.
de Candia
Antonio
A
Coniglio
Antonio
A
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D058225:Plaque, Amyloid / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
D000682:Amyloid