Effect of packing density of lipid vesicles on the Aβ42 fibril polymorphism

Chae Eun Heo; Chae Ri Park; Hugh I. Kim

doi:10.1016/j.chemphyslip.2021.105073

Effect of packing density of lipid vesicles on the Aβ42 fibril polymorphism

Chae Eun Heo, Chae Ri Park, Hugh I. Kim^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

The aggregation of amyloid-β 1–42 (Aβ42) on lipid membranes is closely related to the pathology of Alzheimer's disease (AD). Herein, we demonstrated the effect of the packing density of lipid vesicles on the Aβ42 fibrillation kinetics and fibril morphology. We used three distinct phosphatidylcholine (PC) lipids, containing different numbers of cis-double bonds in acyl chains, and therefore, a different packing density in the lipid vesicles. Our results showed that the fibrillation of Aβ42 was greatly enhanced and the formed fibrils became shorter as the number of double bonds in lipids increased. Due to the low-density characteristics of dioleoyl phosphatidylcholine (DOPC), Aβ42 monomers were able to interact with the hydrophobic acyl chain of lipids exposed to the aqueous phase, thereby inducing rapid fibrillation and short fibril morphologies. Furthermore, the effects of the anionic lipids dioleoyl phosphatidylserine (DOPS) and dioleoyl phosphatidylglycerol (DOPG), and mixed vesicles of DOPC/DOPS and DOPC/DOPG on Aβ42 fibrillations were investigated. The tight binding of Aβ42 to the lipid head groups via electrostatic interactions was able to suppress the modulation of Aβ42 fibrillations compared to accelerated fibrillations on loosely packed membranes. Our proposed mechanism regarding the influence of lipid packing density on Aβ42 fibrillations provides an advanced understanding of lipid-associated amyloid fibrillations.

Original language	English
Article number	105073
Journal	Chemistry and Physics of Lipids
Volume	236
DOIs	https://doi.org/10.1016/j.chemphyslip.2021.105073
Publication status	Published - 2021 May

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (NRF) of Korea ( 2019R1A2C2086193 ). This research was also supported by the Korea Basic Science Institute (KBSI) National Research Facilities & Equipment Center (NFEC) , funded by the Korean government (Ministry of Education) ( 2019R1A6C1010028 , 2020R1A6C103A027 ). The authors thank the National Center for Seoul National University Research Facilities for their assistance with the TEM measurements.

Funding Information:
This work was supported by the National Research Foundation (NRF) of Korea (2019R1A2C2086193). This research was also supported by the Korea Basic Science Institute (KBSI)National Research Facilities & Equipment Center (NFEC), funded by the Korean government (Ministry of Education) (2019R1A6C1010028, 2020R1A6C103A027). The authors thank the National Center for Seoul National University Research Facilities for their assistance with the TEM measurements.

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

Amyloid fibrillation
Amyloid-β
Lipid associated amyloid fibrillation
Packing density
Phosphatidylcholine
Polymorphism

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Cell Biology

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10.1016/j.chemphyslip.2021.105073

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@article{257db123e1024267a72eeb8241ef2f77,

title = "Effect of packing density of lipid vesicles on the Aβ42 fibril polymorphism",

abstract = "The aggregation of amyloid-β 1–42 (Aβ42) on lipid membranes is closely related to the pathology of Alzheimer's disease (AD). Herein, we demonstrated the effect of the packing density of lipid vesicles on the Aβ42 fibrillation kinetics and fibril morphology. We used three distinct phosphatidylcholine (PC) lipids, containing different numbers of cis-double bonds in acyl chains, and therefore, a different packing density in the lipid vesicles. Our results showed that the fibrillation of Aβ42 was greatly enhanced and the formed fibrils became shorter as the number of double bonds in lipids increased. Due to the low-density characteristics of dioleoyl phosphatidylcholine (DOPC), Aβ42 monomers were able to interact with the hydrophobic acyl chain of lipids exposed to the aqueous phase, thereby inducing rapid fibrillation and short fibril morphologies. Furthermore, the effects of the anionic lipids dioleoyl phosphatidylserine (DOPS) and dioleoyl phosphatidylglycerol (DOPG), and mixed vesicles of DOPC/DOPS and DOPC/DOPG on Aβ42 fibrillations were investigated. The tight binding of Aβ42 to the lipid head groups via electrostatic interactions was able to suppress the modulation of Aβ42 fibrillations compared to accelerated fibrillations on loosely packed membranes. Our proposed mechanism regarding the influence of lipid packing density on Aβ42 fibrillations provides an advanced understanding of lipid-associated amyloid fibrillations.",

keywords = "Amyloid fibrillation, Amyloid-β, Lipid associated amyloid fibrillation, Packing density, Phosphatidylcholine, Polymorphism",

author = "Heo, \{Chae Eun\} and Park, \{Chae Ri\} and Kim, \{Hugh I.\}",

note = "Funding Information: This work was supported by the National Research Foundation (NRF) of Korea ( 2019R1A2C2086193 ). This research was also supported by the Korea Basic Science Institute (KBSI) National Research Facilities \& Equipment Center (NFEC) , funded by the Korean government (Ministry of Education) ( 2019R1A6C1010028 , 2020R1A6C103A027 ). The authors thank the National Center for Seoul National University Research Facilities for their assistance with the TEM measurements. Funding Information: This work was supported by the National Research Foundation (NRF) of Korea (2019R1A2C2086193). This research was also supported by the Korea Basic Science Institute (KBSI)National Research Facilities \& Equipment Center (NFEC), funded by the Korean government (Ministry of Education) (2019R1A6C1010028, 2020R1A6C103A027). The authors thank the National Center for Seoul National University Research Facilities for their assistance with the TEM measurements. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",

year = "2021",

month = may,

doi = "10.1016/j.chemphyslip.2021.105073",

language = "English",

volume = "236",

journal = "Chemistry and Physics of Lipids",

issn = "0009-3084",

publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Effect of packing density of lipid vesicles on the Aβ42 fibril polymorphism

AU - Heo, Chae Eun

AU - Park, Chae Ri

AU - Kim, Hugh I.

N1 - Funding Information: This work was supported by the National Research Foundation (NRF) of Korea ( 2019R1A2C2086193 ). This research was also supported by the Korea Basic Science Institute (KBSI) National Research Facilities & Equipment Center (NFEC) , funded by the Korean government (Ministry of Education) ( 2019R1A6C1010028 , 2020R1A6C103A027 ). The authors thank the National Center for Seoul National University Research Facilities for their assistance with the TEM measurements. Funding Information: This work was supported by the National Research Foundation (NRF) of Korea (2019R1A2C2086193). This research was also supported by the Korea Basic Science Institute (KBSI)National Research Facilities & Equipment Center (NFEC), funded by the Korean government (Ministry of Education) (2019R1A6C1010028, 2020R1A6C103A027). The authors thank the National Center for Seoul National University Research Facilities for their assistance with the TEM measurements. Publisher Copyright: © 2021 Elsevier B.V.

PY - 2021/5

Y1 - 2021/5

N2 - The aggregation of amyloid-β 1–42 (Aβ42) on lipid membranes is closely related to the pathology of Alzheimer's disease (AD). Herein, we demonstrated the effect of the packing density of lipid vesicles on the Aβ42 fibrillation kinetics and fibril morphology. We used three distinct phosphatidylcholine (PC) lipids, containing different numbers of cis-double bonds in acyl chains, and therefore, a different packing density in the lipid vesicles. Our results showed that the fibrillation of Aβ42 was greatly enhanced and the formed fibrils became shorter as the number of double bonds in lipids increased. Due to the low-density characteristics of dioleoyl phosphatidylcholine (DOPC), Aβ42 monomers were able to interact with the hydrophobic acyl chain of lipids exposed to the aqueous phase, thereby inducing rapid fibrillation and short fibril morphologies. Furthermore, the effects of the anionic lipids dioleoyl phosphatidylserine (DOPS) and dioleoyl phosphatidylglycerol (DOPG), and mixed vesicles of DOPC/DOPS and DOPC/DOPG on Aβ42 fibrillations were investigated. The tight binding of Aβ42 to the lipid head groups via electrostatic interactions was able to suppress the modulation of Aβ42 fibrillations compared to accelerated fibrillations on loosely packed membranes. Our proposed mechanism regarding the influence of lipid packing density on Aβ42 fibrillations provides an advanced understanding of lipid-associated amyloid fibrillations.

AB - The aggregation of amyloid-β 1–42 (Aβ42) on lipid membranes is closely related to the pathology of Alzheimer's disease (AD). Herein, we demonstrated the effect of the packing density of lipid vesicles on the Aβ42 fibrillation kinetics and fibril morphology. We used three distinct phosphatidylcholine (PC) lipids, containing different numbers of cis-double bonds in acyl chains, and therefore, a different packing density in the lipid vesicles. Our results showed that the fibrillation of Aβ42 was greatly enhanced and the formed fibrils became shorter as the number of double bonds in lipids increased. Due to the low-density characteristics of dioleoyl phosphatidylcholine (DOPC), Aβ42 monomers were able to interact with the hydrophobic acyl chain of lipids exposed to the aqueous phase, thereby inducing rapid fibrillation and short fibril morphologies. Furthermore, the effects of the anionic lipids dioleoyl phosphatidylserine (DOPS) and dioleoyl phosphatidylglycerol (DOPG), and mixed vesicles of DOPC/DOPS and DOPC/DOPG on Aβ42 fibrillations were investigated. The tight binding of Aβ42 to the lipid head groups via electrostatic interactions was able to suppress the modulation of Aβ42 fibrillations compared to accelerated fibrillations on loosely packed membranes. Our proposed mechanism regarding the influence of lipid packing density on Aβ42 fibrillations provides an advanced understanding of lipid-associated amyloid fibrillations.

KW - Amyloid fibrillation

KW - Amyloid-β

KW - Lipid associated amyloid fibrillation

KW - Packing density

KW - Phosphatidylcholine

KW - Polymorphism

UR - https://www.scopus.com/pages/publications/85102608162

U2 - 10.1016/j.chemphyslip.2021.105073

DO - 10.1016/j.chemphyslip.2021.105073

M3 - Article

C2 - 33675780

AN - SCOPUS:85102608162

SN - 0009-3084

VL - 236

JO - Chemistry and Physics of Lipids

JF - Chemistry and Physics of Lipids

M1 - 105073

ER -

Effect of packing density of lipid vesicles on the Aβ42 fibril polymorphism

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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