Thermodynamic stability and critical points in multicomponent mixtures with structured interactions

Graf, Isabella R.; Machta, Benjamin B.

doi:10.1103/physrevresearch.4.033144

Cited by 15 publications

(17 citation statements)

References 44 publications

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“…The formation of many different phases can be studied elegantly when molecules are provided by reservoirs ( 37 – 39 ), but phase coexistence cannot be directly examined with this method. Instead, random matrix theory has been used to unveil parameter regimes of multicomponent fluids that lead to many coexisting phases ( 36 , 40 – 43 ). However, it is unclear how well random interactions capture real proteins, which have evolved for millions of generations.…”

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confidence: 99%

Evolved interactions stabilize many coexisting phases in multicomponent liquids

Zwicker

Laan

2022

Proc. Natl. Acad. Sci. U.S.A.

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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.

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confidence: 99%

Evolved interactions stabilize many coexisting phases in multicomponent liquids

Zwicker

Laan

2022

Proc. Natl. Acad. Sci. U.S.A.

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“…The relationship between this ansatz and findings from sequence-dependent theories will be discussed in Section IV. The work of ref has also suggested a useful method for coarse-graining a multicomponent fluid into an equivalent binary mixture with the same spinodal and critical points by preserving the second and third cumulants along the first principal component of the concentration-weighted feature distribution. However, it is unclear whether the coexistence manifolds of multicomponent mixtures with low-rank interaction matrices can be simplified in the same way.…”

Section: Predicting and Designing Phase Behavior In Multicomponent Fl...mentioning

confidence: 99%

Theory and Simulation of Multiphase Coexistence in Biomolecular Mixtures

Jacobs

2023

J. Chem. Theory Comput.

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Biomolecular condensates constitute a newly recognized form of spatial organization in living cells. Although many condensates are believed to form as a result of phase separation, the physicochemical properties that determine the phase behavior of heterogeneous biomolecular mixtures are only beginning to be explored. Theory and simulation provide invaluable tools for probing the relationship between molecular determinants, such as protein and RNA sequences, and the emergence of phase-separated condensates in such complex environments. This review covers recent advances in the prediction and computational design of biomolecular mixtures that phase-separate into many coexisting phases. First, we review efforts to understand the phase behavior of mixtures with hundreds or thousands of species using theoretical models and statistical approaches. We then describe progress in developing analytical theories and coarse-grained simulation models to predict multiphase condensates with the molecular detail required to make contact with biophysical experiments. We conclude by summarizing the challenges ahead for modeling the inhomogeneous spatial organization of biomolecular mixtures in living cells.

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“…Although it is not surprising that heteropolymers can phase separate at high concentrations, it is remarkable that LLPS can establish coexisting condensates with distinct molecular compositions required for carrying out specific biological functions [10,11]. Despite recent progress in modeling multicomponent phase separation [12][13][14][15][16][17][18][19], the relationship between the "design space" of such specific interactions and the capacity for biological fluids to selforganize into chemically diverse droplets via LLPS remains poorly understood.…”

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confidence: 99%

Programmable phase behavior in fluids with designable interactions

Chen¹,

Jacobs²

2023

Preprint

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Intracellular fluids can self-organize into phase-separated condensates as a result of evolved biomolecular interactions. However, the extent to which the equilibrium phase behavior of a complex fluid can be controlled by tuning such interactions remains unclear. Here we apply convex optimization to design fluids that demix into phases with prescribed compositions at thermodynamic equilibrium. We then show how multicomponent phase diagrams can differ qualitatively from those of simple fluids. Our approach enables the rational design of multicomponent fluids with phase diagrams of arbitrary complexity.

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Thermodynamic stability and critical points in multicomponent mixtures with structured interactions

Cited by 15 publications

References 44 publications

Evolved interactions stabilize many coexisting phases in multicomponent liquids

Evolved interactions stabilize many coexisting phases in multicomponent liquids

Theory and Simulation of Multiphase Coexistence in Biomolecular Mixtures

Programmable phase behavior in fluids with designable interactions

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