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NACore Amyloid Formation in the Presence of Phospholipids

Pallbo, Jon LU ; Imai, Masayuki ; Gentile, Luigi LU ; Takata, Shin Ichi ; Olsson, Ulf LU and Sparr, Emma LU (2020) In Frontiers in Physiology 11.
Abstract

Amyloids are implicated in many diseases, and disruption of lipid membrane structures is considered as one possible mechanism of pathology. In this paper we investigate interactions between an aggregating peptide and phospholipid membranes, focusing on the nanometer-scale structures of the aggregates formed, as well as on the effect on the aggregation process. As a model system, we use the small amyloid-forming peptide named NACore, which is a fragment of the central region of the protein α-synuclein that is associated with Parkinson’s disease. We find that phospholipid vesicles readily associate with the amyloid fibril network in the form of highly distorted and trapped vesicles that also may wet the surface of the fibrils. This effect... (More)

Amyloids are implicated in many diseases, and disruption of lipid membrane structures is considered as one possible mechanism of pathology. In this paper we investigate interactions between an aggregating peptide and phospholipid membranes, focusing on the nanometer-scale structures of the aggregates formed, as well as on the effect on the aggregation process. As a model system, we use the small amyloid-forming peptide named NACore, which is a fragment of the central region of the protein α-synuclein that is associated with Parkinson’s disease. We find that phospholipid vesicles readily associate with the amyloid fibril network in the form of highly distorted and trapped vesicles that also may wet the surface of the fibrils. This effect is most pronounced for model lipid systems containing only zwitterionic lipids. Fibrillation is found to be retarded by the presence of the vesicles. At the resolution of our measurements, which are based mainly on cryogenic transmission electron microscopy (cryo-TEM), X-ray scattering, and circular dichroism (CD) spectroscopy, we find that the resulting aggregates can be well fitted as linear combinations of peptide fibrils and phospholipid bilayers. There are no detectable effects on the cross-β packing of the peptide molecules in the fibrils, or on the thickness of the phospholipid bilayers. This suggests that while the peptide fibrils and lipid bilayers readily co-assemble on large length-scales, most of them still retain their separate structural identities on molecular length-scales. Comparison between this relatively simple model system and other amyloid systems might help distinguish aspects of amyloid-lipid interactions that are generic from aspects that are more protein specific. Finally, we briefly consider possible implications of the obtained results for in-vivo amyloid toxicity.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aggregation, amyloids, bilayers, fibrillation, lipids, NACore, peptides, vesicles
in
Frontiers in Physiology
volume
11
article number
592117
publisher
Frontiers Media S. A.
external identifiers
  • pmid:33391013
  • scopus:85098700094
ISSN
1664-042X
DOI
10.3389/fphys.2020.592117
language
English
LU publication?
yes
id
bfb98069-3a42-4134-a386-2b1ee1de8952
date added to LUP
2021-01-15 07:21:27
date last changed
2021-04-13 05:22:44
@article{bfb98069-3a42-4134-a386-2b1ee1de8952,
  abstract     = {<p>Amyloids are implicated in many diseases, and disruption of lipid membrane structures is considered as one possible mechanism of pathology. In this paper we investigate interactions between an aggregating peptide and phospholipid membranes, focusing on the nanometer-scale structures of the aggregates formed, as well as on the effect on the aggregation process. As a model system, we use the small amyloid-forming peptide named NACore, which is a fragment of the central region of the protein α-synuclein that is associated with Parkinson’s disease. We find that phospholipid vesicles readily associate with the amyloid fibril network in the form of highly distorted and trapped vesicles that also may wet the surface of the fibrils. This effect is most pronounced for model lipid systems containing only zwitterionic lipids. Fibrillation is found to be retarded by the presence of the vesicles. At the resolution of our measurements, which are based mainly on cryogenic transmission electron microscopy (cryo-TEM), X-ray scattering, and circular dichroism (CD) spectroscopy, we find that the resulting aggregates can be well fitted as linear combinations of peptide fibrils and phospholipid bilayers. There are no detectable effects on the cross-β packing of the peptide molecules in the fibrils, or on the thickness of the phospholipid bilayers. This suggests that while the peptide fibrils and lipid bilayers readily co-assemble on large length-scales, most of them still retain their separate structural identities on molecular length-scales. Comparison between this relatively simple model system and other amyloid systems might help distinguish aspects of amyloid-lipid interactions that are generic from aspects that are more protein specific. Finally, we briefly consider possible implications of the obtained results for in-vivo amyloid toxicity.</p>},
  author       = {Pallbo, Jon and Imai, Masayuki and Gentile, Luigi and Takata, Shin Ichi and Olsson, Ulf and Sparr, Emma},
  issn         = {1664-042X},
  language     = {eng},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Physiology},
  title        = {NACore Amyloid Formation in the Presence of Phospholipids},
  url          = {http://dx.doi.org/10.3389/fphys.2020.592117},
  doi          = {10.3389/fphys.2020.592117},
  volume       = {11},
  year         = {2020},
}