Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Poster Abstracts

38-POS Board 20 TREHALOSE SUGAR PROTECTS LIPID MEMBRANE AGAINST AMYLOID-BETA TOXICITY IN ALZHEIMER'S DISEASE Yue Xu 1 ; Danielle M McRae 1 ; Carina T Filice 2,3 ; Zoya Leonenko 1,2,3 ; 1 University of Waterloo, Department of Physics and Astronomy, Waterloo, ON, Canada 2 University of Waterloo, Department of Biology, Waterloo, ON, Canada 3 University of Waterloo, Waterloo Institute of Nanotechnology, Waterloo, ON, Canada The amyloid- beta peptide (Aβ1 -42) is one of the main pathogenic factors in Alzheimer’s disease and is known to induce damage to the lipid membrane (Drolle et al. 2017). Trehalose, a naturally existing disaccharide, has been shown to protect plant cellular membranes in extreme conditions and has been attracting attention in neurodegeneration research due to its ability to reduce Aβ misfolding (Khan and Kumar, 2017). We hypothesize that trehalose can also protect the neuronal membrane from amyloid toxicity. In this work, we aimed to explore the potential protective effect of trehalose against Aβ -induced damage in model lipid membranes (DPPC/POPC/Cholesterol in mass ratio of 4:4:2), used to mimic neuronal membranes. We used atomic force microscopy (AFM), Kelvin Probe Force Microscopy (KPFM), Black lipid membrane (BLM) and Localized Surface Plasmon Resonance (LSPR) techniques. Our AFM and KPFM results demonstrated that trehalose modifies the properties of model lipid membranes and monolayers (both topography and electrical surface potential), especially in combination with NaCl. Our BLM data show that Aβ induced damage to membranes and led to ionic current leakage across membranes due to the formation of various defects and pores. The presence of trehalose reduced the ion current caused by Aβ peptides’ damage to membranes. Our LSPR results revealed that trehalose potentially reduces the binding of Aβ to lipid membranes, indicating the protective effect through suppression of Aβ -membrane interaction. These findings suggest that trehalose sugar can be useful in protecting neuronal cellular membranes against amyloid toxicity, and thus, this study may contribute to the development of membrane-targeted preventive approaches to overcome AD.

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