Abstract

Soluble protein oligomers have only recently been shown to be a better predictor of cell cytotoxicity compared to insoluble fibrils, however the intrinsic heterogeneity of oligomers makes them difficult to characterize using ensemble biophysical techniques alone. For example, methods to separate proteins by size, such as SDS-PAGE or size exclusion chromatography, have largely been inadequate to describe oligomers, and do not recapitulate apparent oligomer sizes in electron micrographs. Similarly, the use of denaturing detergents (e.g., SDS) can actively induce protein oligomerization, thereby perturbing the states one wishes to measure.

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