Interaction of the tau fibrils with the neuronal membrane

Chowdhury, Unmesh D.; Paul, Arnav; Bhargava, B. L.

doi:10.1016/j.bpc.2023.107024

Cited by 1 publication

(2 citation statements)

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“…Hence, we looked into the possible docking mechanism of the tau fibril over the PI domains on the bilayer. 34,66 Figure 10 shows the snapshots of the interaction of tau filament (PHF) with PI lipids at different timeframes. R349 and K353 residues are shown along with a neighbouring PI lipid.…”

Section: Resultsmentioning

confidence: 99%

“…33 Also, we have studied the effect of tau polymorphs on the model neuronal membrane comprising of six different lipid components. 34 But due to the lack of study on the effect of PI lipids on the interaction of tau fibril with the lipid bilayer, we carried out all-atom and coarse-grained molecular dynamics simulations taking a similar starting configuration. In the subsequent sections, PC, PG and PI are used to refer to POPC, POPG and PIP 2 lipids, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Phosphatidylinositol (PI) Lipids Modulate the Binding of Tau Fibrils on Lipid Bilayers

Chowdhury,

Paul,

Bhargava

2023

Preprint

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Phosphatidylinositol (PI) lipids play a crucial role as a vital lipid component in cell membrane domain formation, contributing to cell signaling. In this study, we investigate the impact of PI lipids on the conformational dynamics of tubulin-associated unit (tau) fibrils through multiscale modelling. While prior experimental work by the Lecomte group has demonstrated the influence of PI lipids on the morphology and secondary structure of tau fragments, a detailed molecular understanding of the binding mechanism between tau and PI-incorporated lipids remains absent. Our molecular dynamics (MD) simulations reveal the intricate molecular mechanisms governing tau binding to PI-incorporated bilayers. Specifically, we conduct MD simulations on lipid patches containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (PG), enabling us to explore conformational changes in the R3--R4 section of tau fibrils. Control simulations are conducted on pure lipid patches without tau fibrils, as well as on tau fibrils within bulk water. Our findings demonstrate that PI-incorporated lipids exhibit a stronger affinity for binding to tau fibrils compared to pure PC/PG lipids. All-atom simulations highlight the potential docking sites for PI headgroups at positively charged residues (Lysine, Arginine) on the tau surface. Moreover, the aggregation of PI lipids facilitates tau binding to the membrane. These results not only enhance our comprehension of the disruption of PI-incorporated bilayers, but also shed light on the stability of the tau over the PI containing bilayers.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%