Modulation of Lipid Dynamics in the ß-Amyloid Aggregates Induced Membrane Fragmentation.
J Phys Chem B
; 128(23): 5667-5675, 2024 Jun 13.
Article
em En
| MEDLINE
| ID: mdl-38836448
ABSTRACT
Nonspecific membrane disruption is considered a plausible mechanism for the cytotoxicity induced by ß-amyloid (Aß) aggregates. In scenarios of high local Aß concentrations, a two-step membrane fragmentation model has been proposed. Initially, membrane-embedded Aß oligomeric aggregates form, followed by membrane fragmentation. However, the key molecular-level interactions between Aß oligomeric aggregates and lipids that drive the second-stage membrane fragmentation remain unclear. This study monitors the time-dependent changes in lipid dynamics and water accessibility of model liposomes during Aß-induced membrane fragmentation. Our results indicate that lipid dynamics on the nanosecond to microsecond time scale undergo rapid acceleration upon initial incubation with membrane-incorporated Aß oligomeric aggregates, followed by a slow deceleration process. Concurrently, lipid headgroups become less accessible to water. Both observations suggest a carpet-like mechanism of membrane disruption for the Aß-induced membrane fragmentation process.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
Idioma:
En
Revista:
J Phys Chem B
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos