The aggregation of proteins into amyloid fibrils is of key importance for many diseases. Amyloid is an abnormal, insoluble protein that accumulates in tissues and organs, leading to their damage and dysfunction. It is a characteristic feature of a group of diseases called amyloidoses. Fibrillar proteins are a heterogeneous group of elongated structural proteins, diverse in structure, location and function. They are characterised by a tendency to form fibres, known as fibrils, poor solubility in water and resistance to enzymes. Despite their key role in amyloid formation, the role of spin interactions in this process has never been studied before.
As a result of cooperation between the Institute of Physics of the Polish Academy of Sciences and the Hebrew University of Jerusalem, new aspects of the formation of the A-β(1-42) polypeptide amyloid, associated e.g. with Alzheimer's disease, have been discovered. In spite of its key role in amyloid formation, the role of spin interactions in this process was never explored.
Our research shows that spin polarisation, associated with the Chiral Induced Spin Selectivity (CISS) effect, plays a significant role in the formation of amyloid-like fibrils. Notably, electron spin effects are rather unexpected in biological systems due to their size and fragmentation. The average length of a single fibril is 200 nm, and aggregation is 1-100 μm in size. Both are much longer than the expected distance for spin effects under these conditions, which is typically in the nanometre range.
This surprising relationship is probably related to a change in the dynamics of the self-assembly process through dipole interactions during protein self-organisation. Using different spin-polarised interfaces, through the adsorption of proteins on a magnetic substrate, we observe a preferential orientation of the magnetisation for fibril formation. It results in up to twice as many fibrils being formed and significantly longer fibrils in the favored magnetisation. So, by tailoring the spin-polarized interface, we were able to control the amyloid assembly process. In addition, structural changes such as shifts between oligomers to mature fibrils were observed, highlighting the unexpected role of spin interactions in protein structural dynamics.
These findings not only provide insight into an additional mechanism behind amyloid formation, but also open possibilities for the use of magnetic particles in therapeutic strategies for amyloid-related disorders. In particular, using magnetic nanoparticles to selectively affect amyloid formation in the treatment of neurodegenerative diseases and the use of spin-selective interfaces in dialysis systems to alleviate amyloidosis.
