Full-length Tau disrupts fluid zwitterionic supported lipid bilayers
Abstract
The Tau protein is involved in several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Under physiological conditions, Tau binds to microtubules and participates in neuronal integrity. Under pathological conditions, Tau misfolds and aggregates into insoluble amyloid fibers, ultimately leading to neuronal death. Most studies have focused on Tau aggregation promoted by negatively charged cofactors such as anionic lipids or polyanions, while its interactions with neutral membrane components have received less attention. Notably, phosphatidylcholine (PC), the most abundant zwitterionic phospholipid in the plasma membrane, has been detected within Tau aggregates in vivo, and Tau can directly interact with membranes through their lipid or protein components. Here, we investigated the interaction between Tau and PC-containing model membranes using polarized infrared spectroscopy and atomic force microscopy. Supported bilayers composed of DOPC, mixed DOPC:DPPC, and DPPC containing cholesterol were used to modulate membrane fluidity. Our results show that Tau binds to and perturbs PC membranes only when sufficient fluidity is present, while retaining its native structural conformation. These findings highlight a previously underexplored aspect of Tau-membrane interactions and suggest that the physical state of the membrane may play a key role in modulating Tau pathogenicity.
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BibTeX
@article{urythiery2026fulllength,
title = {{Full-length Tau disrupts fluid zwitterionic supported lipid bilayers}},
author = {Vicky Ury-Thiery and Michael Molinari and Sophie Lecomte and Cécile Feuillie},
journal = {Biophysical Chemistry},
year = {2026},
month = oct,
doi = {10.1016/j.bpc.2026.107626},
url = {https://hal.science/hal-05826669v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Full-length Tau disrupts fluid zwitterionic supported lipid bilayers
AU - Vicky Ury-Thiery
AU - Michael Molinari
AU - Sophie Lecomte
AU - Cécile Feuillie
PY - 2026
DA - 2026/10/20
JO - Biophysical Chemistry
DO - 10.1016/j.bpc.2026.107626
UR - https://hal.science/hal-05826669v1
AB - The Tau protein is involved in several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Under physiological conditions, Tau binds to microtubules and participates in neuronal integrity. Under pathological conditions, Tau misfolds and aggregates into insoluble amyloid fibers, ultimately leading to neuronal death. Most studies have focused on Tau aggregation promoted by negatively charged cofactors such as anionic lipids or polyanions, while its interactions with neutral membrane components have received less attention. Notably, phosphatidylcholine (PC), the most abundant zwitterionic phospholipid in the plasma membrane, has been detected within Tau aggregates in vivo, and Tau can directly interact with membranes through their lipid or protein components. Here, we investigated the interaction between Tau and PC-containing model membranes using polarized infrared spectroscopy and atomic force microscopy. Supported bilayers composed of DOPC, mixed DOPC:DPPC, and DPPC containing cholesterol were used to modulate membrane fluidity. Our results show that Tau binds to and perturbs PC membranes only when sufficient fluidity is present, while retaining its native structural conformation. These findings highlight a previously underexplored aspect of Tau-membrane interactions and suggest that the physical state of the membrane may play a key role in modulating Tau pathogenicity.
SN - 0301-4622
ER -