Impact of Lipid Composition and Synergistic Effect on Aβ42 Oligomer-Induced Changes in Membrane Conductance and Microviscosity.
- 1Institute of Biochemistry, Life Sciences Center, Vilnius University, Saulėtekio av. 7, VilniusLT-10257, Lithuania.
- 2Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio av. 7, VilniusLT-10257, Lithuania.
Abstract
The accumulation of the Aβ42 peptide is one of the key factors in the progression of Alzheimer's disease, as it disrupts synaptic signaling and impairs neuronal function. Although the peptide is known to compromise plasma membrane integrity, the detailed mechanisms underlying bilayer alterations and lipid-Aβ42 interactions remain unclear. In the present study, electrochemical impedance spectroscopy and fluorescence lifetime imaging microscopy were employed to investigate the impact of oligomeric Aβ42 on model membranes that mimic the lipid composition of the outer leaflet of the neuronal plasma membrane. Our results demonstrate that the presence of SM or GM1 within a DOPC/Chol backbone is enough to facilitate Aβ42 interaction with the membrane, as evidenced by increased membrane microviscosity; however, this interaction alone is insufficient to induce permeability-enhancing defects in the membrane. Extensive disruption of bilayer integrity required the complete lipid ensemble present in the outer leaflet of the neuronal membrane-mimicking composition, indicating that not only specific lipids but also their cooperative interplay and organization within the lipid bilayer are essential for Aβ42-induced membrane permeabilization.
Related
- Neuronal lipid composition regulates distinct states of full-length tau assembly, mechanics and membrane interactions
- Age-Related Lens Membrane Composition and N101D Deamidation Modulate αA-Crystallin Membrane Interactions Relevant to Cataract.
- Fluorescence-Based Microviscosity Mapping in Membraneless Organelles
- Membrane lipid composition is associated with differential sensitivity to apigenin in U937 and HL-60 cells: insights from cell-based and Langmuir monolayer studies
- State-selective inhibition of alpha-synuclein aggregation by de novo oligomer-binding proteins
BibTeX
@article{jankaitytė2026impact,
title = {{Impact of Lipid Composition and Synergistic Effect on Aβ42 Oligomer-Induced Changes in Membrane Conductance and Microviscosity.}},
author = {Evelina Jankaitytė and Artu̅ras Polita and Andrius Sakalauskas and Rimgailė Tamulytė and Vytautas Smirnovas and Rima Budvytyte},
journal = {ACS chemical neuroscience},
year = {2026},
month = sep,
doi = {10.1021/acschemneuro.6c00244},
url = {https://europepmc.org/article/MED/42915572},
note = {CC BY},
}
RIS
TY - JOUR
TI - Impact of Lipid Composition and Synergistic Effect on Aβ42 Oligomer-Induced Changes in Membrane Conductance and Microviscosity.
AU - Evelina Jankaitytė
AU - Artu̅ras Polita
AU - Andrius Sakalauskas
AU - Rimgailė Tamulytė
AU - Vytautas Smirnovas
AU - Rima Budvytyte
PY - 2026
DA - 2026/09/01
JO - ACS chemical neuroscience
DO - 10.1021/acschemneuro.6c00244
UR - https://europepmc.org/article/MED/42915572
AB - The accumulation of the Aβ42 peptide is one of the key factors in the progression of Alzheimer's disease, as it disrupts synaptic signaling and impairs neuronal function. Although the peptide is known to compromise plasma membrane integrity, the detailed mechanisms underlying bilayer alterations and lipid-Aβ42 interactions remain unclear. In the present study, electrochemical impedance spectroscopy and fluorescence lifetime imaging microscopy were employed to investigate the impact of oligomeric Aβ42 on model membranes that mimic the lipid composition of the outer leaflet of the neuronal plasma membrane. Our results demonstrate that the presence of SM or GM1 within a DOPC/Chol backbone is enough to facilitate Aβ42 interaction with the membrane, as evidenced by increased membrane microviscosity; however, this interaction alone is insufficient to induce permeability-enhancing defects in the membrane. Extensive disruption of bilayer integrity required the complete lipid ensemble present in the outer leaflet of the neuronal membrane-mimicking composition, indicating that not only specific lipids but also their cooperative interplay and organization within the lipid bilayer are essential for Aβ42-induced membrane permeabilization.
SN - 1948-7193
ER -