Modulation of the Phospholipid Dynamics and Bilayer Water Accessibility with the Membrane-Associated Nucleation of β-Amyloid (Aβ) Peptides

Authors: Brian Lum, Wei Qiang

Field of Study: Biochemistry

Program Affiliation: McNair Scholars Program

Faculty Mentors: Wei Qiang

Easel: 51

Timeslot: Midday

Abstract: Aggregating beta-amyloid (Aβ) peptide disrupting cell membranes in the human brain is considered a primary cytotoxic mechanism by which cell death occurs in patients with Alzheimer's disease (AD). However, the underlying structural basis for these disruptive interactions remains poorly understood. By utilizing solid-state nuclear magnetic resonance (ssNMR) spectroscopy, the molecular dynamics of phospholipids within membrane bilayers in response to early-stage Aβ-membrane interactions can be quantified, which provides useful insights into how the intermediate states of membrane-associated Aβ aggregation interact and disrupt the membrane. Aꞵ 40 and Aꞵ 42 peptide isoforms were incubated with three types of model phospholipid vesicles. Samples were collected at four intermediate time points before the onset of fibrillation and subjected to ssNMR measurements. The results demonstrate a general rigidification of bilayers and the formation of local defects upon interaction with Aꞵ compared to controls, with modulation effects quantitatively more significant after interaction with Aꞵ 42 compared to Aꞵ 40 .