Stacey D. Wetmore
Professor, Tier I Board of Governors Research Chair at the University of Lethbridge
BSc, Mount Allison University
PhD, Dalhousie University
Postdoc, Australian National University
Computer Modeling of DNA Repair
Zoya Leonenko
Department of Physics and Astronomy,
Department of Biology
Waterloo Institute for Nanotechnology,
University of Waterloo
Diploma (MS), Novosibirsk State University, Russia
PhD, Novosibirsk State University, Russia
Biophysical study of Alzheimer’s disease
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by dementia and memory loss for which no cure or prevention is available. Amyloid toxicity is a result of the non-specific interaction of toxic amyloid oligomers with the plasma membrane.
We studied amyloid aggregation and interaction of amyloid beta (1-42) peptide with lipid membrane using atomic force microscopy (AFM), Kelvin probe force microscopy, surface Plasmon resonance (SPR) and Black Lipid Membrane (BLM). Using AFM-based atomic force spectroscopy (AFS) we measured the binging forces between two single amyloid peptide molecules and showed that novel pseudo-peptide inhibitors SG effectively prevent amyloid-amyloid binding on a single molecule level. We demonstrated that lipid membrane plays an active role in amyloid binding and toxicity: changes in membrane composition and properties increase amyloid binding and toxicity. Effect of lipid composition, the presence of cholesterol and melatonin are discussed. We discovered that membrane cholesterol creates nanoscale electrostatic domains which induce preferential binding of amyloid peptide, while membrane melatonin reduces amyloid-membrane interactions, protecting the membrane from amyloid damage. These findings contribute to better understanding molecular mechanism of Alzheimer’s disease and aid into developments of novel strategies for cure and prevention of AD.