Interaction of the tau fibrils with the neuronal membrane.

Unmesh D Chowdhury, Arnav Paul, B L Bhargava

Biophysical chemistry 2023 Jul

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Tau proteins are recently gaining a lot of interest due to their active role in causing a range of tauopathies. Molecular mechanisms underlying the tau interaction with the neuronal membrane are hitherto unknown and difficult to characterize using experimental methods. Using the cryo-EM structure of the tau-fibrils we have used atomistic molecular dynamics simulation to model the tau fibril and neuronal membrane interaction using explicit solvation. The dynamics and structural characteristics of the tau fibril with the neuronal membrane are compared to the tau fibril in the aqueous phase to corroborate the effect of the neuronal membrane in the tau structure. Tau fibrils have been modelled using CHARMM-36m force field and the six component neuronal membrane composition is taken from the earlier simulation results. The timescale conceivable in our molecular dynamics simulations is of the order of microseconds which captures the onset of the interaction of the tau fibrils with the neuronal membrane. This interaction is found to impact the tau pathogenesis that finally causes neuronal toxicity. Our study initiates the understanding of tau conformational ensemble in the presence of neuronal membrane and sheds the light on the significant tau-membrane interactions. Copyright © 2023 Elsevier B.V. All rights reserved.