Alzheimer’s disease is a common form of dementia that affects about 5 million people in the United States of America. A wealth of data links the disease to the misfolding and clumping of the Aβ peptide. The precise mode by which the aggregates induce toxicity, however, is unknown. Recent findings suggest that cell membrane disruption induced by Aβ aggregates triggers cytotoxicity. The goal of our research project is to gain insight into the mechanism by which Aβ aggregates perturb the local environment of model plasma membranes. We use coarse grain molecular dynamics simulations to monitor the interactions of the aggregate at different levels of insertion in model membranes. Our preliminary results suggest that the aggregate’s motion is modulated by the relative orientation and surface electrostatics of the protofilament. These observations shed light on the stability of the aggregate’s insertion mode and the mechanism of membrane disruption.

Driving forces of the stability of Alzheimer’s Aβ aggregates in model membranes

249th National Meeting (2015)

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