Spatially non-uniform condensates emerge from dynamically arrested phase separation

Biomolecular condensates with internal structure allow cells to further organise their processes. In this work the authors investigate how condensates can obtain an internal structure with droplets of dilute phase inside via kinetic, rather than purely thermodynamic driving forces. The formation of biomolecular condensates through phase separation from proteins and nucleic acids is emerging as a spatial organisational principle used broadly by living cells. Many such biomolecular condensates are not, however, homogeneous fluids, but possess an internal structure consisting of distinct sub-compartments with different compositions. Notably, condensates can contain compartments that are depleted in the biopolymers that make up the condensate. Here, we show that such double-emulsion condensates emerge via dynamically arrested phase transitions. The combination of a change in composition coupled with a slow response to this change can lead to the nucleation of biopolymer-poor droplets within the polymer-rich condensate phase. Our findings demonstrate that condensates with a complex internal architecture can arise from kinetic, rather than purely thermodynamic driving forces, and provide more generally an avenue to understand and control the internal structure of condensates in vitro and in vivo.

Automated summary

In this study, the authors investigate how biomolecular condensates can form an internal structure with dilute phase droplets via kinetic driving forces. The formation of biomolecular condensates through phase separation from proteins and nucleic acids is widely used by cells as a spatial organizational principle. This study demonstrates that complex internal architecture of condensates can arise from kinetic driving forces, providing insights into understanding and controlling the structure of condensates in vitro and in vivo.