Thermodynamics of amyloid formation and the role of intersheet interactions

Summary, in English

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. (C) 2015 AIP Publishing LLC.

• Författare: Anders Irbäck; Jonas Wessén
• Avdelning/ar: Beräkningsbiologi och biologisk fysik - Har omorganiserats; Teoretisk partikelfysik - Har omorganiserats
• Publiceringsår: 2015
• Språk: Engelska
• Publikation/Tidskrift/Serie: Journal of Chemical Physics
• Volym: 143
• Issue: 10
• Länkar: http://dx.doi.org/10.1063/1.4930280
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Institute of Physics (AIP)
• Ämne: Other Physics Topics; Biophysics
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0021-9606