What do ßamyloid, buckyballs, and dark matter have in common? They were all mentioned in an intriguing presentation by Dr. Westlind-Danielsson (AstraZeneca, Abstract 299.2) on the formation of spheroidal "supramolecular structures" by amyloid 1-40 under "near-physiological conditions (50mM NaHPO.NaHPO, pH7.4, 100mM NaCl at 30oC)". These "ßamy-balls" (in honor of the buckyballs formed by buckminsterfullerene) range in diameter from 20-200 µm (similar in size to AD plaques) and consist of 6-10 nm diameter fibrils. They are stable for up to three weeks and, if left to dry, form an intriguing network-like structure (reminiscent of the large scale structure of the universe based on the distribution of dark matter and the lattice of buckyballs). They do not form from pure Aß1-42, although mixtures of the two amyloid peptides do give rise to the structures.
Perhaps what is most remarkable about amy-balls is that they form in a completely cell-free environment. In other words, this molecular behavior arises from the biochemical features of this peptide, which has been known for many years to spontaneously form fibrils. Other aggregating peptides do not show the same behavior under the same conditions. A century ago, D’Arcy Thompson was a proponent of the importance of understanding physical constraints on biological systems. His opus, "On Growth and Form", emphasized the molding influence of physico-chemical forces on the shape and function of cells and larger organisms. The amy-balls are reminiscent of such phenomena and may provide a means of modeling some of the physical properties of the spheroidal pathological features found in a variety of neurodegenerative diseases, including Alzheimer’s plaques. Certainly, the fact that such structures emerge spontaneously in a test tube point to the possibility that some of the structure of plaques could be due to similar physicochemical forces. What it may reveal about the large scale structure of dark matter in the universe will no doubt require further investigation. (I’d love to see the grant proposal for that!)-Keith Crutcher.
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