Self-Assembly of Biomolecular Condensates with Shared Components

Biomolecular condensates self-assemble when proteins and nucleic acids spontaneously demix to form droplets within the crowded intracellular milieu. This simple mechanism underlies the formation of a wide variety of membraneless compartments in living cells. To understand how multiple condensates with distinct compositions can self-assemble in such a heterogeneous system, which may not be at thermodynamic equilibrium, we study a minimal model in which we can program the pairwise interactions among hundreds of species. We show that the number of distinct condensates that can be reliably assembled grows superlincarly with the number of species in the mixture when the condensates share components. Furthermore, we show that we can predict the maximum number of distinct condensates in a mixture without knowing the details of the pairwise interactions. Simulations of condensate growth confirm these predictions and suggest that the physical rules governing the achievable complexity of condensate-mediated spatial organization are broadly applicable to biomolecular mixtures.

Automated summary

Biomolecular condensates are droplets formed by proteins and nucleic acids spontaneously separating in the crowded intracellular environment, serving as the foundation for membraneless compartments in cells. Research shows that in a system that may not be at thermodynamic equilibrium, the number of reliably assembled distinct condensates increases superlinearly with the number of species when they share components. Additionally, it is possible to predict the maximum number of distinct condensates in a mixture without knowing the details of pairwise interactions.