Wolfram Ponisch

How droplets affect the irreversible formation of linear aggregates

The formation of membrane-less compartments resulting from liquid-liquid phase separation has been observed in many biological systems, yet their role in the formation of linear aggregates, such as cytoskeletal proteins or amyloids, remains unclear. In this talk, we will explore how the internal properties of droplets can control linear aggregation.
We will focus on the impact of droplet rheology, which refers to the ability of monomers and aggregates to move within and be exchanged between the droplets. Using a kinetic theory of the irreversible aggregation of dilute fibrils interacting with proteins undergoing phase separation, we will examine how the rheology of the droplets influences the distribution of aggregate as a function of size. Our results demonstrate that depending on the mobility of the monomers and aggregates, the distribution of monomers and fibrils can exhibit a switch-like behaviour.
Our findings suggest that by inducing liquid-liquid phase separation and altering the properties of the resulting compartments, a cell may be able to control linear aggregation, which could be utilized to confine cytotoxic protein aggregates. As a result, our work may shed light on new strategies for developing treatments for protein misfolding diseases.
In summary, this talk will present our latest research on the role of membrane-less compartments in linear aggregation and demonstrate the potential for controlling this process through droplet rheology and liquid-liquid phase separation.