Low MW Peptide Oligomers at Medium and High Resolution
Low molecular weight oligomers of the amyloid beta 1-42 peptide, aBeta 42, implicated in Alzheimer’s Disease, are relatively compact and have significant order where none has been previously observed. |
Medium resolution in 500 nm fields
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The smallest soluble low MW oligomers are indicated by arrows.
Lateral dimensions (corrected for tip width). range from 5 - 10 nm and heights from 1 - 3 nm.
The scale bar is coded to show small differences in height.
Imaging is in phosphate buffer using super sharp silicon tips.
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High resolution in 150 nm fields
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In 150 nm fields, higher resolution imaging is possible. Distinct elements are visible in soluble oligomers of the Alzheimer’s peptide aBeta42 that may correspond to monomers in the process of forming the cross B-sheet structure characteristic of mature protofibrils.
Top molecules are color-coded for height, as indicated in the bar. Below, continuous color is used to better see finer structure.
The largest oligomer contains four distinct ridges; the next smallest molecule at one-half the length has two ridges.
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The drawings interpret the early oligomers according to models proposed by the Tycko and Reik groups based on NMR studies of aBeta structures. In the monomer, two beta-strand segments are separated by a bend and the N-terminal amino acids are thought to be disordered.
Interestingly, height (1.5 - 2 nm), widths (6 - 8 the nm) and disordered regions in the AFM images are similar to the model. The length is greater perhaps due to incomplete cross B-sheet formation between monomers.
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