Full-length Tau disrupts fluid zwitterionic supported lipid bilayers.

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• The Tau protein is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's.
• Pathological Tau misfolding and aggregation into amyloid fibers lead to neuronal death.
• Research has primarily focused on Tau aggregation with charged molecules, neglecting neutral membrane interactions.

Purpose of the Study:

• To investigate the interaction between Tau protein and phosphatidylcholine (PC)-containing model membranes.
• To understand how membrane fluidity influences Tau binding and structural conformation.
• To explore a novel aspect of Tau-membrane interactions in the context of neurodegeneration.

Main Methods:

• Utilized polarized infrared spectroscopy and atomic force microscopy.
• Employed supported lipid bilayers of varying compositions (DOPC, DOPC:DPPC, DPPC with cholesterol) to control membrane fluidity.
• Analyzed Tau's interaction with model membranes under different physical states.

Main Results:

• Tau protein binds to and perturbs PC membranes.
• This interaction and perturbation occur specifically when the membrane exhibits sufficient fluidity.
• Tau maintains its native structural conformation during binding to fluid PC membranes.

Conclusions:

• Membrane fluidity, particularly in phosphatidylcholine bilayers, is a key factor modulating Tau-membrane interactions.
• Underexplored interactions with neutral membrane components like PC may significantly influence Tau pathogenicity.
• The physical state of the cell membrane could be a critical determinant in the progression of Tau-related neurodegenerative diseases.