Molecular rotors report on changes of live cell plasma membrane microviscosity upon interaction with beta-amyloid aggregates
File(s) manuscript_final plus methods.pdf (928.86 KB)
Accepted version
Author(s)
Kuimova, Marina
Kubankova, Marketa
Kiryushko, Darya
Lopez Duarte, Ismael
Type
Journal Article
Abstract
Amyloid deposits of aggregated beta-amyloid Aβ(1–42) peptides are a pathological hallmark of Alzheimer's disease. Aβ(1–42) aggregates are known to induce biophysical alterations in cells, including disruption of plasma membranes. We investigated the microviscosity of plasma membranes upon interaction with oligomeric and fibrillar forms of Aβ(1–42). Viscosity-sensing fluorophores termed molecular rotors were utilised to directly measure the microviscosities of giant plasma membrane vesicles (GPMVs) and plasma membranes of live SH-SY5Y and HeLa cells. The fluorescence lifetimes of membrane-inserting BODIPY-based molecular rotors revealed a decrease in bilayer microviscosity upon incubation with Aβ(1–42) oligomers, while fibrillar Aβ(1–42) did not significantly affect the microviscosity of the bilayer. In addition, we demonstrate that the neuroprotective peptide H3 counteracts the microviscosity change induced by Aβ(1–42) oligomers, suggesting the utility of H3 as a neuroprotective therapeutic agent in neurodegenerative disorders and indicating that ligand-induced membrane stabilisation may be a possible mechanism of neuroprotection during neurodegenerative disorders such as Alzheimer's disease.
Date Issued
2018-12-14
Date Acceptance
2018-10-26
Citation
Soft Matter, 2018, 14 (46), pp.9466-9474
ISSN
1744-683X
Publisher
Royal Society of Chemistry
Start Page
9466
End Page
9474
Journal / Book Title
Soft Matter
Volume
14
Issue
46
Copyright Statement
© The Royal Society of Chemistry 2018
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Grant Number
EP/I003983/1
EP/K030760/1
n/a
Subjects
Science & Technology
Physical Sciences
Technology
Chemistry, Physical
Materials Science, Multidisciplinary
Physics, Multidisciplinary
Polymer Science
Chemistry
Materials Science
Physics
ALZHEIMERS-DISEASE
HOMEOVISCOUS ADAPTATION
BIOLOGICAL-MEMBRANES
LIPID-COMPOSITION
PHASE-SEPARATION
PROTEIN
VISCOSITY
OLIGOMERS
FLUIDITY
PEPTIDE
Amyloid beta-Peptides
Boron Compounds
Cell Line, Tumor
Cell Membrane
Fluorescent Dyes
Humans
Neuropeptides
Peptide Fragments
Viscosity
03 Chemical Sciences
09 Engineering
02 Physical Sciences
Chemical Physics
Publication Status
Published
Date Publish Online
2018-10-31
