The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth

• Published in: PLoS computational biology Vol. 16; no. 5; p. e1007767
• Main Authors: van Gils, Juami Hermine Mariama, van Dijk, Erik, Peduzzo, Alessia, Hofmann, Alexander, Vettore, Nicola, Schützmann, Marie P., Groth, Georg, Mouhib, Halima, Otzen, Daniel E., Buell, Alexander K., Abeln, Sanne
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.05.2020; PLOS; Public Library of Science (PLoS)
• Subjects: Amyloid; Bioinformatics; Biological research; Biology; Biology and Life Sciences; Chemical properties; Chemical Sciences; Compensation; Computer science; Data analysis; Denaturation; Disease; Elongation; Entropy; Experiments; Fibrils; Funding; Glycoproteins; Heat; Hydrophobic effect; Hydrophobicity; Movement disorders; Neurodegenerative diseases; Observations; or physical chemistry; Parkinson's disease; Peptides; Physical Sciences; Physiological aspects; Physiology; Polymers; Protein folding; Proteins; Research and Analysis Methods; Signatures; Simulation; Software; Stability; Temperature dependence; Temperature effects; Theoretical and; Thermal properties; Thermodynamics; Netherlands; Denmark; Germany
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1007767

Many proteins have the potential to aggregate into amyloid fibrils, protein polymers associated with a wide range of human disorders such as Alzheimer's and Parkinson's disease. The thermodynamic stability of amyloid fibrils, in contrast to that of folded proteins, is not well understood: the balance between entropic and enthalpic terms, including the chain entropy and the hydrophobic effect, are poorly characterised. Using a combination of theory, in vitro experiments, simulations of a coarse-grained protein model and meta-data analysis, we delineate the enthalpic and entropic contributions that dominate amyloid fibril elongation. Our prediction of a characteristic temperature-dependent enthalpic signature is confirmed by the performed calorimetric experiments and a meta-analysis over published data. From these results we are able to define the necessary conditions to observe cold denaturation of amyloid fibrils. Overall, we show that amyloid fibril elongation is associated with a negative heat capacity, the magnitude of which correlates closely with the hydrophobic surface area that is buried upon fibril formation, highlighting the importance of hydrophobicity for fibril stability.