SFB Transregio 102: Polymers under multiple constraints: restricted and controlled molecular order and mobility

Sub-project:  “Amyloid protein aggregation and fibril formation near interfaces and nanoparticles“

The molecular mechanisms of amyloid peptide and protein aggregation are still not very well understood. There is growing concern that nanoparticles may catalyze amyloid protein aggregation and thus cause amyloid related diseases. In the previous funding period we have discovered that metal nanoparticles

(external constraint) may accelerate short amyloid peptide aggregation and fibrillation. We have found a nucleation mechanism starting with biomolecule interaction, adsorption, and selforganization in a nanoparticle peptide corona that seeds amyloid peptide/protein aggregation and fibrillation and ends up in large fibrils embedding the nanoparticles. Interestingly, also similar but not exactly matching templates induce fast fibrillation, causing a cross-seeding effect. We specifically aim at (spectroscopic) investigations of the biomolecule corona (structure, composition, dynamics, and function), the cross-seeding effect, as well as answeringthe question, whether catalysis of fibrillation though nanoparticles is indeed a general effect orif also situations exist, in which nanoparticles act as inhibitors. Toxicity studies may help to rationalize the observed effect in vitro. Finally, we aim at developing simple coarse-grained models for the molecularunderstanding of the effect of nanoparticles on the mechanism of aggregation and fibrillation ofamyloid systems.