Molecular rotors report on changes in live cell plasma membrane microviscosity upon interaction with beta-amyloid aggregates

Soft Matter. 2018 Nov 28;14(46):9466-9474. doi: 10.1039/c8sm01633j.


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.

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Boron Compounds / pharmacology*
  • Cell Line, Tumor
  • Cell Membrane / drug effects*
  • Cell Membrane / physiology
  • Fluorescent Dyes / pharmacology*
  • Humans
  • Neuropeptides / pharmacology
  • Peptide Fragments / pharmacology*
  • Viscosity


  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Amyloid beta-Peptides
  • Boron Compounds
  • Fluorescent Dyes
  • Neuropeptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)