C17.2 cells take up aggregated Tau. A, recombinant MTBR Tau
was prepared in vitro and induced to fibrillize using arachidonic
acid. Tau monomer is not detectable via AFM. After 24 h of incubation with
arachidonic acid, however, Tau is highly aggregated, forming many oligomeric
and fibrillar species. Scale bars, 600 nm. B, aggregated Tau
was treated with buffer or 0.125% trypsin for 1 min and resolved by SDS-PAGE
4–15% gradient gel, followed by Coomassie stain. Aggregated Tau is very
sensitive to trypsin digestion. C, C17.2 cells were exposed to
AF488-containing buffer, AF488-labeled monomer, or aggregates. After 3 and 9
h, cells were harvested by 0.25% trypsin treatment. Intracellular AF488
fluorescence was then quantified by flow cytometry. After 3 h, 2.0% of
monomer-treated cells scored positive, versus 18% for
aggregate-treated cells. After 9 h, 3.0% of monomer-treated cells scored
positive, versus 22% for aggregate-treated cells. *,
p < 10-6 (unpaired t test, n = 4,
10,000 cells counted per experiment). D, MTBR-AF488 aggregate-treated
C17.2 cells with or without trypsin treatment and visualized by confocal
microscopy. Scale bar, 30 μm. E, MTBR-AF488
aggregate-treated C17.2 cell stained for tubulin and visualized via confocal
microscopy after treatment with 0.25% trypsin illustrates internalized
aggregates. Arrows indicate displacement of tubulin. An
apical-to-distal slice (bar) obtained from a three-dimensional image
rendered from Z-stacks shows MTBR-AF488 in the same plane as tubulin.
Scale bar, 10 μm.