FIGURE 2.

Simplified overview on phase separation and aggregation. (A) Upon presence of scaffold proteins with potent liquid-liquid phase separation (LLPS)-enabling features, de-mixing of a protein solution can take place, eventuation in liquid-like condensates, consisting of both scaffold (dark blue) and client (light blue) proteins. Ageing processes result in solid-like condensates that no longer support dynamic exchange of constituents with the surrounding milieu. Please note that also chaperones and protein quality control factors are involved in these processes. (B) Unfolded resp. partially unfolded protein species can adopt different aggregate forms. Depending on the intrinsic nature, amorphous as well as amyloid aggregates can occur, with a limited potential for recovery. Small heats hock proteins (sHsps) are responsible for targeted and regulated sequestration and alleviate subsequent recovery/refolding.