The amyloid-cell membrane system. The interplay between the biophysical features of oligomers/fibrils and cell membrane defines amyloid toxicity

- Amyloid aggregation and aggregate cytotoxicity are generic properties of any polypeptide chain.
- A close relation between amyloid biophysical features and cytotoxicity does exist.
- Biological surfaces are important inductors of protein misfolding/aggregation and sites of amyloid interaction.
- A close relation between cell membrane biophysical features and amyloid cytotoxicity does exist.
- Amyloid cytotoxicity appears as an emerging property depending on the biophysical features of the amyloid-membrane system.

Amyloid cytotoxicity, structure and polymorphisms are themes of increasing importance. Present knowledge considers any peptide/protein able to undergo misfolding and aggregation generating intrinsically cytotoxic amyloids. It also describes growth and structure of amyloid fibrils and their possible disassembly, whereas reduced information is available on oligomer structure. Recent research has highlighted the importance of the environmental conditions as determinants of the amyloid polymorphisms and cytotoxicity. Another body of evidence describes chemical or biological surfaces as key sites of protein misfolding and aggregation or of interaction with amyloids and the resulting biochemical modifications inducing cell functional/viability impairment. In particular, the membrane lipid composition appears to modulate cell response to toxic amyloids, thus contributing to explain the variable vulnerability to the same amyloids of different cell types. Finally, a recent view describes amyloid toxicity as an emerging property dependent on a complex interplay between the biophysical features of early aggregates and the interacting cell membranes taken as a whole system.