Evolved interactions stabilize many coexisting phases in multicomponent liquids

Abstract

Phase separation has emerged as an essential concept for the spatial organization inside biological cells. However, despite the clear relevance to virtually all physiological functions, we understand surprisingly little about what phases form in a system of many interacting components, like in cells. Here we introduce a numerical method based on physical relaxation dynamics to study the coexisting phases in such systems. We use our approach to optimize interactions between components, similar to how evolution might have optimized the interactions of proteins. These evolved interactions robustly lead to a defined number of phases, despite substantial uncertainties in the initial composition, while random or designed interactions perform much worse. Moreover, the optimized interactions are robust to perturbations, and they allow fast adaption to new target phase counts. We thus show that genetically encoded interactions of proteins provide versatile control of phase behavior. The phases forming in our system are also a concrete example of a robust emergent property that does not rely on fine-tuning the parameters of individual constituents.

Phase Transitions of Associative Biomacromolecules

“…The constraints refer to concentrations that cannot change due to the nature of the system. If there are n ph possible coexisting phases, 240 then for fixed temperature and pressure, there are n df thermodynamic degrees of freedom in the system. This is estimated as n df = n am − n con − n ph .…”

Dynamical control enables the formation of demixed biomolecular condensates

“…Biomolecular condensates arise via spontaneous and driven phase transitions of complex mixtures of multivalent protein and RNA molecules 1–5 . A key challenge is understanding how condensates with shared and distinct macromolecular compositions can coexist as distinct functional entities 6 ( Figure 1a ). The importance of this issue is emphasized by observations in the filamentous fungus Ashbya gossypii where Langdon et al, 7 reported the presence of coexisting ribonucleoprotein condensates that share the protein Whi3.…”

Open questions on liquid–liquid phase separation

“…Moreover, mixtures of phase-separating molecules can exhibit synergy or interference of LLPS. In general, multicomponent mixtures are more likely to separate in multiple coexisting phases and those phases are more robust to fluctuations in the number or concentration of components 5 . Nevertheless, a deeper understanding of LLPS and multiphase organization in complex mixtures is required, as protocell organization may underlie their function as reactors.…”