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

Area of Science:

• Neuroscience
• Biophysics
• Cell Biology

Background:

• Alzheimer's disease is characterized by amyloid deposits of beta-amyloid (Aβ(1-42)) peptides.
• Aβ(1-42) aggregates can alter cell biophysics, including plasma membrane integrity.

Purpose of the Study:

• To investigate how oligomeric and fibrillar Aβ(1-42) forms affect plasma membrane microviscosity.
• To evaluate the neuroprotective peptide H3's ability to counteract Aβ(1-42)-induced membrane alterations.

Main Methods:

• Utilized viscosity-sensing molecular rotors (BODIPY-based fluorophores) to measure membrane microviscosity.
• Applied molecular rotors to giant plasma membrane vesicles (GPMVs) and live SH-SY5Y and HeLa cells.
• Measured fluorescence lifetimes to determine changes in bilayer microviscosity.

Main Results:

• Oligomeric Aβ(1-42) significantly decreased plasma membrane microviscosity.
• Fibrillar Aβ(1-42) did not cause a significant change in membrane microviscosity.
• The neuroprotective peptide H3 effectively counteracted the microviscosity reduction induced by Aβ(1-42) oligomers.

Conclusions:

• Aβ(1-42) oligomers, not fibrils, reduce membrane microviscosity, indicating a specific pathological mechanism.
• Peptide H3 demonstrates neuroprotective potential by stabilizing cell membranes against Aβ(1-42) oligomer damage.
• Ligand-induced membrane stabilization is a potential therapeutic strategy for neurodegenerative diseases like Alzheimer's.