Colorimetric Detection of Mutant β-Amyloid(1-40) Membrane-Active Aggregation with Biosensing Vesicles

Area of Science:

• Neuroscience
• Biochemistry
• Materials Science

Background:

• Alzheimer's disease (AD) is linked to amyloid-beta (Aβ) protein misfolding and aggregation.
• Toxic Aβ aggregates form nanoscale species, progressing from oligomers to fibrils.
• Understanding Aβ interaction with lipid membranes is crucial for AD pathogenesis.

Purpose of the Study:

• To develop a rapid, colorimetric biosensor for detecting Aβ peptide aggregation and membrane interactions.
• To investigate how familial AD-associated Aβ mutations influence aggregation and lipid binding.
• To gain insights into the role of cellular surfaces in AD progression.

Main Methods:

• Utilized lipid/polydiacetylene (PDA) vesicles as biomimetic biosensors.
• Exposed vesicles to wild-type and mutant Aβ(1-40) peptides.
• Employed time-resolved colorimetric measurements, atomic force microscopy, and Thioflavin T assays.

Main Results:

• The biosensor directly detected Aβ peptide-lipid interaction events, particularly with mutant forms.
• Aβ(1-40) aggregate membrane activity varied significantly among peptide variants and lipid compositions.
• Distinct stages of Aβ(1-40) aggregate formation, morphology, and membrane activity were characterized.

Conclusions:

• Developed a simple, effective colorimetric assay for detecting Aβ aggregation and membrane interactions.
• Demonstrated that Aβ variants and lipid composition modulate membrane activity.
• Provided insights into the role of cellular surfaces in Alzheimer's disease mechanisms.