Thermodynamics of amyloid formation and the role of intersheet interactions

TL;DR

This study uses a minimal lattice model and advanced simulation techniques to investigate the thermodynamics of amyloid fibril formation, revealing a phase transition driven by intersheet interactions that promote multi-layered fibril growth.

Contribution

It introduces a thermodynamic analysis of amyloid formation with a focus on intersheet interactions using a lattice model and Monte Carlo methods, highlighting the conditions for fibril growth and phase transitions.

Findings

Lateral intersheet interactions lead to a phase transition between solution and fibril states.

Intermediate-sized aggregates are statistically suppressed.

One-dimensional growth does not exhibit the same thermodynamic properties.

Abstract

The self-assembly of proteins into $\beta$-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.