Event Description
Ari Gafni, PhD,
Department of Biophysics, University of Michigan
“Single Molecule Fluorescence Studies of Amyloid Beta Membrane Interactions”
The amyloid-β (Aβ) peptide features in the synaptic dysfunction and neuronal loss associated with Alzheimer’s disease. The mechanism underlying the synaptic dysfunction likely involves the formation of Aβ oligomeric structures on the neuronal membrane that, by permeabilizing the membrane disrupt homeostasis causing cell death. We aim to identify the molecular species that feature in the cytotoxicity and to reveal their mechanism of action. To this end we are using single molecule total internal reflection fluorescence microscopy to follow the formation, diffusion and interaction of individual Aβ oligomers with both synthetic membranes and live cells. These studies allow us to use nanomolar Aβ concentrations, as found in vivo, and provide detailed information on the role of peptide-membrane interactions in the formation and growth of the Aβ oligomers that feature in Alzheimer’s pathology. Interactions between two distinct Aβ peptide species, Aβ40 and Aβ42 reveal additional complexity of oligomer formation trajectory. Surprisingly, none of the studies where physiological Aβ concentrations are used reveal toxicity towards cultured neurons.
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