Two timescales control the creation of large protein aggregates in cells

TL;DR

This study identifies two distinct physical timescales governing protein aggregate formation in cells, revealing how diffusion and active forces influence aggregation size and dynamics, with implications for cellular organization and disease.

Contribution

The paper combines experimental and theoretical approaches to uncover two physical timescales that control protein aggregation in cells, highlighting the role of diffusion and active forces.

Findings

Fast aggregation of small clusters due to diffusion

Large aggregates experience slowed growth due to pore size constraints

Active forces may continue to stir aggregates despite slow diffusion

Abstract

Protein aggregation is of particular interest due to its connection with many diseases and disorders. Many factors can alter the dynamics and result of this process, one of them being the diffusivity of the monomers and aggregates in the system. Here, we study experimentally and theoretically an aggregation process in cells, and we identify two distinct physical timescales that set the number and size of aggregates. The first timescale involves fast aggregation of small clusters freely diffusing in the cytoplasm, while, in the second one, the aggregates are larger than the pore size of the cytoplasm and thus barely diffuse, and the aggregation process is slowed down. However, the process is not entirely halted, potentially reflecting a myriad of active but random forces forces that stir the aggregates. Such slow timescale is essential to account for the experimental results of the aggregation process. These results could also have implications in other processes of spatial organization in cell biology, such as phase-separated droplets.