Date/Time
Date(s) - 16/04/2013
2:30 pm - 3:30 pm

Title: Molecular mechanisms of amyloid fibril formation and toxicity in relation to Alzheimerâ??s disease.

Speaker: Dr. Zoya Leonekno

Institute: University of Waterloo

Location: ABB 271

Description:

Amyloid fibrils are insoluble protein aggregates in beta-sheet conformation that are implicated in at least 20 diseases, such as Alzheimerâ??s, for which no cure is currently available. Molecular mechanism of amyloid fibril formation and toxicity is not well understood, and the role of cell membrane surfaces is not known. We used atomic force microscopy, frequency modulated Kelvin probe microscopy, force spectroscopy, neutron scattering and Langmuir-Blodgett monolayer techniques to study amyloid beta (1-42) binding and fibril formation on model lipid
membranes. Effect of lipid composition, surface charge and presence of cholesterol and melatonin are discussed. We show that lipid membrane readily binds amyloid, which affects its structure and roughness. Melatonin and cholesterol have the opposite effects of the membrane
properties which affects amyoid binding and toxicity. We applied Surface Plasmon Resonance (SPR) combined with microfluidics and Surface Enhanced Raman Spectroscopy (SERS)to understand the protective effect of melatonin. We also used single molecule force spectroscopy to study binding of two individual amyloid-β (1-42) molecules, and showed that with the addition of Cu ions the rupture force increases and force distribution becomes broader, and with
addition of inhibitor the binding is suppressed.