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Amyloids and Micelles : Self-assembly and co-assembly of Abeta and gangliosides

Hu, Jing LU (2024)
Abstract
Extracellular plaques in Alzheimer’s disease contain Aβ peptides and ganglioside lipids such as GM1. Aβ monomers self-assemble into beta-sheet-rich fibrils when their concentration exceeds solubility, while GM1 monomers form spherical micelles above their critical concentration. This study examines the self-assembly of Aβ in the first two papers and its co-assembly with GM1 in the last two. In Paper I, we investigate whether the secondary nucleation sites of Aβ are defects on fibrils, using the secondary nucleation sites binding chaperone–Brichos. We found that secondary nucleation sites are rare and that fibrils formed under low supersaturation exhibit fewer secondary nucleation sites than those formed under high supersaturation. In Paper... (More)
Extracellular plaques in Alzheimer’s disease contain Aβ peptides and ganglioside lipids such as GM1. Aβ monomers self-assemble into beta-sheet-rich fibrils when their concentration exceeds solubility, while GM1 monomers form spherical micelles above their critical concentration. This study examines the self-assembly of Aβ in the first two papers and its co-assembly with GM1 in the last two. In Paper I, we investigate whether the secondary nucleation sites of Aβ are defects on fibrils, using the secondary nucleation sites binding chaperone–Brichos. We found that secondary nucleation sites are rare and that fibrils formed under low supersaturation exhibit fewer secondary nucleation sites than those formed under high supersaturation. In Paper II, we examine the impact of shear force from mild agitation on Aβ kinetics. Our findings show that mild agitation accelerates both primary and secondary nucleation, particularly the detachment step of the latter. Papers III and IV explore the co-assembly of Aβ and GM1 and its effects on Aβ aggregation kinetics and thermodynamics. We found that Aβ and GM1 form micellar co-assemblies, with Aβ evenly distributed among co-assemblies, likely positioned at the interface between GM1’s hydrophobic chains and head groups. This co-assembly reduces both the aggregation speed and solubility of Aβ. (Less)
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author
supervisor
opponent
  • Associate professor Lendel, Christofer, KTH Royal Institute of Technology.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Amyloid Beta, ganglioside lipids, kinetic, thermodynamic
pages
165 pages
publisher
Lund University
defense location
KC:A. Join via zoom: https://lu-se.zoom.us/j/61647037626
defense date
2025-01-31 09:00:00
ISBN
978-91-8096-088-5
978-91-8096-089-2
language
English
LU publication?
yes
id
befe5b07-c369-4a91-92b9-d941ecc179ac
date added to LUP
2025-01-07 10:21:18
date last changed
2025-04-04 15:06:28
@phdthesis{befe5b07-c369-4a91-92b9-d941ecc179ac,
  abstract     = {{Extracellular plaques in Alzheimer’s disease contain Aβ peptides and ganglioside lipids such as GM1. Aβ monomers self-assemble into beta-sheet-rich fibrils when their concentration exceeds solubility, while GM1 monomers form spherical micelles above their critical concentration. This study examines the self-assembly of Aβ in the first two papers and its co-assembly with GM1 in the last two. In Paper I, we investigate whether the secondary nucleation sites of Aβ are defects on fibrils, using the secondary nucleation sites binding chaperone–Brichos. We found that secondary nucleation sites are rare and that fibrils formed under low supersaturation exhibit fewer secondary nucleation sites than those formed under high supersaturation. In Paper II, we examine the impact of shear force from mild agitation on Aβ kinetics. Our findings show that mild agitation accelerates both primary and secondary nucleation, particularly the detachment step of the latter. Papers III and IV explore the co-assembly of Aβ and GM1 and its effects on Aβ aggregation kinetics and thermodynamics. We found that Aβ and GM1 form micellar co-assemblies, with Aβ evenly distributed among co-assemblies, likely positioned at the interface between GM1’s hydrophobic chains and head groups. This co-assembly reduces both the aggregation speed and solubility of Aβ.}},
  author       = {{Hu, Jing}},
  isbn         = {{978-91-8096-088-5}},
  keywords     = {{Amyloid Beta; ganglioside lipids; kinetic; thermodynamic}},
  language     = {{eng}},
  publisher    = {{Lund University}},
  school       = {{Lund University}},
  title        = {{Amyloids and Micelles : Self-assembly and co-assembly of Abeta and gangliosides}},
  url          = {{https://lup.lub.lu.se/search/files/204406750/Jing_Hu_-_WEBB.pdf}},
  year         = {{2024}},
}