In this paper, we ask the following molecular recognition-related question: ‘when two proteins aggregate under the same conditions, do they homo-aggregate with likenesses of themselves, or do they hetero-aggregate, with chains sections of one protein forming intermolecular beta sheets with the chain sections of another protein?’. We take differentially fluorescently-labelled forms of two proteins that aggregate, under similar conditions, into amyloid-like microstructures (even if these are in amorphous ‘macro’ forms initially) and show that they are uniformly hetero-aggregated, to the extent that this can be resolved through confocal fluorescence microscopy examining small volumes within aggregates. Each volume examined contains about a million protein chains, and within this resolution, all sections of the aggregates show fluorescence signals derived from both chains, suggesting hetero-aggregation. Of course, it must be mentioned that this technique would probably not work with proteins that retain significant native structure while aggregating, because such proteins would very likely homo-aggregate by recognizing likenesses of chains possessing the same identity.

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