AVS 58th Annual International Symposium and Exhibition
    Neutron Scattering Focus Topic Wednesday Sessions
       Session NT+AS-WeA

Invited Paper NT+AS-WeA8
Interaction of Alzheimer’s Disease Tau Protein with Model Lipid Membranes

Wednesday, November 2, 2011, 4:20 pm, Room 207

Session: Applications of Neutron Scattering II
Presenter: Eva Y. Chi, Univ. of New Mexico
Authors: E.M. Jones, Univ. of New Mexico
M. Dubey, Los Alamos National Lab
P.J. Camp, Univ. of New Mexico
B.C. Givler, Univ. of New Mexico
J. Biernat, Max Planck Unit for Structural Biology, Germany
E. Mandelkow, Max Planck Unit for Structural Biology, Germany
J. Majewski, Los Alamos National Lab
E.Y. Chi, Univ. of New Mexico
Correspondent: Click to Email
In addition to amyloid plaques, tau neurofibrillary tangles comprise another pathological hallmark of Alzheimer's disease (AD). The mechanism of tau’s misfolding and aggregation is unknown, but evidence suggests that tau in AD brains may abnormally interact with the neuronal cell membrane. Using lipid monolayers at the air/water interface and supported lipid bilayers as model membrane systems, we characterized the interaction between 4 tau constructs with membranes of different lipid compositions and elucidated the structure of the protein-membrane films using a combination of biophysical techniques, including pressure-area isotherms, fluorescence microscopy, and x-ray and neutron scattering. Our data show that the full length human tau (hTau40) and its constructs are highly surface active and exhibited strong association with negative DMPG lipids and induced morphological changes observed with fluorescence microscopy, while exhibiting weaker and no interactions with positive DMTAP and neutral DMPC lipids. To elucidate molecular-scale structural details, we used X-ray scattering techniques to study tau and lipid monolayer association. X-ray reflectivity modeling indicated hTau40’s presence under a DMPG monolayer and partial insertion into the lipid headgroup region, while grazing incidence X-ray diffraction data showed hTau40 insertion disrupted lipid packing. We also used neutron reflectivity assays to investigate hTau40’s ability to disrupt lipid bilayers. The protein completely disrupted a DMPG bilayer while not affecting a neutral DPPC bilayer. These results indicate hTau40 has a propensity to interact with a negatively charged membrane surface and disrupt lipid packing, suggesting a possible protein-aggregate induced mechanism for aggregation and toxicity.