Fig. 11.

Distributions of Aβ₅₅₅ monomers and oligomers under varying sample conditions, as determined by single-molecule stepwise-photobleaching and intensity analysis. The number of peptides per fluorescent spot as determined by HMM analysis as a function of environmental condition are shown. Distributions were obtained from a freshly prepared sample of 10 pM Aβ₅₅₅ in (a) 50 mM Tris buffer (pH8) and (b) after injection of 1.5% (v/v) HFIP after 15 min and (c) 1 h. (d) Representative Aβ₅₅₅ intensity histograms are shown at the beginning (top panel) and end stage (bottom panel) of the oligomerization process. As expected, the oligomerized Aβ₅₅₅ sample has an intensity distribution shifted towards higher values than for the freshly prepared sample. (e) Also shown are the number of peptides-per-oligomer observed for a 10 pM sample of Aβ₅₅₅ in the presence of 1.5% (v/v) HFIP and the oligomer inhibitor BSA (1 μM) after 1 h incubation. Data shown in (a-c and e) is expressed as the mean ± the standard error of the mean from three experimental runs. The histograms in (a), (b), (c) and (e) were constructed from a total of 6808, 1333, 4308 and 1631 fluorescent spots, respectively.