The Effect of Lipid Composition on the Dynamics of Tau Fibrils

Abstract

Knowledge of the interaction of the tau fibrils with the cell membrane is critical for the understanding of the underlying tauopathy pathogenesis. Lipid composition is found to effect the conformational ensemble of the tau fibrils. Using coarse grained and all-atom molecular dynamics simulations we have shown the effect of the lipid composition in modulating the tau structure and dynamics. Molecular dynamics simulations show that tau proteins interact differentially with the zwitterionic compared to the charged lipid membranes. The negatively charged POPG lipid membranes increase the binding affinity of the tau fibrils. The addition of cholesterol is also found to modify the tau binding to the membrane.