title: Thermodynamics of amyloid formation and the role of intersheet interactions.
abstract: The self-assembly of proteins into β-sheet-rich amyloid fibrils has been observed to occur with sigmoidal kinetics, indicating that the system initially is trapped in a metastable state. Here, we use a minimal lattice-based model to explore the thermodynamic forces driving amyloid formation in a finite canonical (NVT) system. By means of generalized-ensemble Monte Carlo techniques and a semi-analytical method, the thermodynamic properties of this model are investigated for different sets of intersheet interaction parameters. When the interactions support lateral growth into multi-layered fibrillar structures, an evaporation/condensation transition is observed, between a supersaturated solution state and a thermodynamically distinct state where small and large fibril-like species exist in equilibrium. Intermediate-size aggregates are statistically suppressed. These properties do not hold if aggregate growth is one-dimensional.
authors.affiliation: Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Irbäck
authors.affiliation: Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Wessén
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D003198:Computer Simulation; D008958:Models, Molecular; D009010:Monte Carlo Method; D055503:Protein Multimerization; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000682:Amyloid; D012996:Solutions