The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth

Erik van Dijk, Juami Hermine Mariama van Gils, Alessia Peduzzo, Alexander Hofmann, Georg Groth, Halima Mouhib, Daniel E. Otzen, Alexander K. Buell, Sanne Abeln

Research output: Contribution to JournalArticleAcademic

Abstract

Many proteins have the potential to aggregate into amyloid fibrils, which are associated with a wide range of human disorders including Alzheimer's and Parkinson's disease. In contrast to that of folded proteins, the thermodynamic stability of amyloid fibrils is not well understood: specifically the balance between entropic and enthalpic terms, including the chain entropy and the hydrophobic effect, are poorly characterised. Using simulations of a coarse-grained protein model we delineate the enthalpic and entropic contributions dominating amyloid fibril elongation, predicting a characteristic temperature-dependent enthalpic signature. We confirm this thermodynamic signature by performing calorimetric experiments and a meta-analysis over published data. From these results, we can also elucidate 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.
Original languageEnglish
JournalarXiv.org
Publication statusPublished - 13 Jun 2019

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thermodynamics
protein
heat capacity
meta-analysis
hydrophobicity
entropy
surface area
simulation
effect
experiment
temperature
cold

Keywords

  • hydrophobicity
  • enthalpy
  • entropy
  • amyloid elongation

Cite this

Dijk, E. V., Gils, J. H. M. V., Peduzzo, A., Hofmann, A., Groth, G., Mouhib, H., ... Abeln, S. (2019). The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth. arXiv.org.
Dijk, Erik van ; Gils, Juami Hermine Mariama van ; Peduzzo, Alessia ; Hofmann, Alexander ; Groth, Georg ; Mouhib, Halima ; Otzen, Daniel E. ; Buell, Alexander K. ; Abeln, Sanne. / The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth. In: arXiv.org. 2019.
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title = "The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth",
abstract = "Many proteins have the potential to aggregate into amyloid fibrils, which are associated with a wide range of human disorders including Alzheimer's and Parkinson's disease. In contrast to that of folded proteins, the thermodynamic stability of amyloid fibrils is not well understood: specifically the balance between entropic and enthalpic terms, including the chain entropy and the hydrophobic effect, are poorly characterised. Using simulations of a coarse-grained protein model we delineate the enthalpic and entropic contributions dominating amyloid fibril elongation, predicting a characteristic temperature-dependent enthalpic signature. We confirm this thermodynamic signature by performing calorimetric experiments and a meta-analysis over published data. From these results, we can also elucidate 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.",
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Dijk, EV, Gils, JHMV, Peduzzo, A, Hofmann, A, Groth, G, Mouhib, H, Otzen, DE, Buell, AK & Abeln, S 2019, 'The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth' arXiv.org.

The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth. / Dijk, Erik van; Gils, Juami Hermine Mariama van; Peduzzo, Alessia; Hofmann, Alexander; Groth, Georg; Mouhib, Halima; Otzen, Daniel E.; Buell, Alexander K.; Abeln, Sanne.

In: arXiv.org, 13.06.2019.

Research output: Contribution to JournalArticleAcademic

TY - JOUR

T1 - The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth

AU - Dijk, Erik van

AU - Gils, Juami Hermine Mariama van

AU - Peduzzo, Alessia

AU - Hofmann, Alexander

AU - Groth, Georg

AU - Mouhib, Halima

AU - Otzen, Daniel E.

AU - Buell, Alexander K.

AU - Abeln, Sanne

PY - 2019/6/13

Y1 - 2019/6/13

N2 - Many proteins have the potential to aggregate into amyloid fibrils, which are associated with a wide range of human disorders including Alzheimer's and Parkinson's disease. In contrast to that of folded proteins, the thermodynamic stability of amyloid fibrils is not well understood: specifically the balance between entropic and enthalpic terms, including the chain entropy and the hydrophobic effect, are poorly characterised. Using simulations of a coarse-grained protein model we delineate the enthalpic and entropic contributions dominating amyloid fibril elongation, predicting a characteristic temperature-dependent enthalpic signature. We confirm this thermodynamic signature by performing calorimetric experiments and a meta-analysis over published data. From these results, we can also elucidate 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.

AB - Many proteins have the potential to aggregate into amyloid fibrils, which are associated with a wide range of human disorders including Alzheimer's and Parkinson's disease. In contrast to that of folded proteins, the thermodynamic stability of amyloid fibrils is not well understood: specifically the balance between entropic and enthalpic terms, including the chain entropy and the hydrophobic effect, are poorly characterised. Using simulations of a coarse-grained protein model we delineate the enthalpic and entropic contributions dominating amyloid fibril elongation, predicting a characteristic temperature-dependent enthalpic signature. We confirm this thermodynamic signature by performing calorimetric experiments and a meta-analysis over published data. From these results, we can also elucidate 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.

KW - hydrophobicity

KW - enthalpy

KW - entropy

KW - amyloid elongation

M3 - Article

JO - arXiv.org

JF - arXiv.org

ER -

Dijk EV, Gils JHMV, Peduzzo A, Hofmann A, Groth G, Mouhib H et al. The hydrophobic effect characterises the thermodynamic signature of amyloid fibril growth. arXiv.org. 2019 Jun 13.