Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Poster Abstracts

35-POS Board 9 INTERACTION OF ΑΜYLOID -BETA PEPTIDES WITH PHOSPHOLIPID BILAYER. Ruan van Deventer 1 ; Yuri Lyubchenko 1 ; 1 University of Nebraska Medical Center, College of Pharmacy, Omaha, NE, USA The amyloid- β peptide, Aβ42, is capable of self -assembly into aggregates of various sizes, and this aggregation process depends on several conditions. Membrane interaction is one of the critical factors involved in the aggregation of Aβ42 at physiological conditions. There is evidence that Aβ42 can change the membrane structure, damaging the membrane through membrane thinning. However, these effects were observed at Aβ42 concentrations significantly higher than physiological, leading to contradictory evidence regarding their relevance. Previously, we have shown that Aβ42, at physiologically relevant low nanomolar concentration, assembles into aggregates but does not damage the bilayer. Here, we investigated the role of the phospholipids' mechanical propertie s on the interaction with Aβ42 aggregates. We used POPC: POPS-supported lipid bilayers (SLB) with different concentrations and employed time-lapse atomic force microscopy (AFM) to directly visualize the effect of Aβ42 on the bilayer morphology. Equimolar POPC: POPS SLBs were assembled at 0.1 mg/ml and 0.25 mg/ml concentrations, and 50 nM of Aβ42 was subsequently incubated on top of the bilayers. In the case of 0.1 mg/ml SLBs, we revealed assembly of oligomers within hours, followed by the formation of pore-like defects, the number of which grew over time. No such effect was observed for 0.25 mg/ml SLBs. The mechanical properties of the bilayers were characterized, where the Young's modulus of 0.1 mg/ml SLBs were half that of 0.25 mg/ml SLBs. These observatio ns suggest that the Aβ42 -induced membrane damage depends on the membrane stiffness, so local mechanical properties of the cell membrane can be a factor resulting in their damage with Aβ42. Membrane damage is considered as one of the factors contributing to the development of Alzheimer's disease, and local mechanical properties of the membrane should be considered as potential factors for disease development.

88