Dataset Information

Graphene quantum dots obstruct the membrane axis of Alzheimer's amyloid beta.

ABSTRACT: Alzheimer's disease (AD) is a primary form of dementia with debilitating consequences, but no effective cure is available. While the pathophysiology of AD remains multifactorial, the aggregation of amyloid beta (Aβ) mediated by the cell membrane is known to be the cause for the neurodegeneration associated with AD. Here we examined the effects of graphene quantum dots (GQDs) on the obstruction of the membrane axis of Aβ in its three representative forms of monomers (Aβ-m), oligomers (Aβ-o), and amyloid fibrils (Aβ-f). Specifically, we determined the membrane fluidity of neuroblastoma SH-SY5Y cells perturbed by the Aβ species, especially by the most toxic Aβ-o, and demonstrated their recovery by GQDs using confocal fluorescence microscopy. Our computational data through discrete molecular dynamics simulations further revealed energetically favorable association of the Aβ species with the GQDs in overcoming peptide-peptide aggregation. Overall, this study positively implicated GQDs as an effective agent in breaking down the membrane axis of Aβ, thereby circumventing adverse downstream events and offering a potential therapeutic solution for AD.

SUBMITTER: Tang H

PROVIDER: S-EPMC8771921 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Graphene quantum dots obstruct the membrane axis of Alzheimer's amyloid beta.

Tang Huayuan H Li Yuhuan Y Kakinen Aleksandr A Andrikopoulos Nicholas N Sun Yunxiang Y Kwak Eunbi E Davis Thomas P TP Ding Feng F Ke Pu Chun PC

Physical chemistry chemical physics : PCCP 20211222 1

Alzheimer's disease (AD) is a primary form of dementia with debilitating consequences, but no effective cure is available. While the pathophysiology of AD remains multifactorial, the aggregation of amyloid beta (Aβ) mediated by the cell membrane is known to be the cause for the neurodegeneration associated with AD. Here we examined the effects of graphene quantum dots (GQDs) on the obstruction of the membrane axis of Aβ in its three representative forms of monomers (Aβ-m), oligomers (Aβ-o), and ...[more]

PMID: 34878460

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Project description:Nanomaterial-biomembrane interactions constitute a critical biological process in assessing the toxicity of such materials in theoretical studies. However, many investigations simplify these interactions by using membrane models containing only one or a few lipid types, deviating significantly from the complexity of real membrane compositions. In particular, cholesterol, a ubiquitous lipid essential for regulating membrane fluidity and closely linked to various diseases, is often overlooked. Consequently, the role of cholesterol in nanomaterial-biomembrane interactions remains poorly understood. In this study, we employ molecular dynamics (MD) simulations to explore the effect of graphene quantum dots (GQDs) on a realistic placental lipid membrane model, aiming to elucidate the role of cholesterol in these interactions. Our MD results reveal that both GQD monomers and clusters can spontaneously insert into the placental lipid membrane model, driven by strong van der Waals interaction energy. Further analyses indicate that cholesterol and POPC lipids primarily contribute to interfacial interactions. Notably, cholesterol can be squeezed into the bilayer interface, forming a unique structure where it is sandwiched between the GQD cluster and the membrane's bottom leaflet. More significantly, cholesterol, together with the GQD cluster, exhibits free lateral movement, suggesting a strong affinity of cholesterol for GQD clusters. These findings highlight the critical role of cholesterol in mediating GQD insertion into the biomembrane. Structural analyses of the membrane further demonstrate deformation of the placental lipid membrane model during GQD penetration. Finally, free energy calculations confirm that the insertion of both GQD monomers and clusters into the placental lipid membrane model is energetically favorable. Overall, this study not only sheds new light on the potential harmful effects of GQDs on realistic placental membranes but also provides the first theoretical evidence of the pivotal role of cholesterol in nanomaterial-biomembrane interactions, contributing to a deeper understanding of nanomaterial-cell membrane interactions.

Dataset Information

Graphene quantum dots obstruct the membrane axis of Alzheimer's amyloid beta.

Publications

Graphene quantum dots obstruct the membrane axis of Alzheimer's amyloid beta.

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