Model biomolecular condensates have heterogeneous structure quantitatively dependent on the interaction profile of their constituent macromolecules

Shillcock, Julian C.; Lagisquet, Clément; Alexandre, Jérémy; Vuillon, Laurent; Ipsen, John Hjort

doi:10.1039/d2sm00387b

Cited by 16 publications

(26 citation statements)

References 147 publications

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“…Recently, Hazra and Levy showed that generic polymers featuring a mixture of long- and short-range interactions are more expanded in dense vs. coexisting dilute phases 37 . Given observations of similar phenomena using very different models 37 , 38 , we analyzed results for variants where we either titrated the number of aromatic stickers or we altered the identities of the aromatic stickers Y vs. F. The goal was to assess the robustness of chain swelling across the phase boundary.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, Shillcock et al 38 , used a specific implementation of graph-theoretical approaches to analyze their simulations of condensates formed off a lattice for generic sticker-and-spacer models. They concluded that the connectivity of condensate networks is much greater than that of random networks, highlighting the fact that these condensates are more elastic than pure fluids.…”

Section: Resultsmentioning

confidence: 99%

“…They concluded that the connectivity of condensate networks is much greater than that of random networks, highlighting the fact that these condensates are more elastic than pure fluids. It is worth noting that the simulations of Shillcock et al 38 , are of model semi-flexible chains in a good solvent. Under these conditions, segregative transitions such as phase separation cannot be realized 25 , 49 .…”

Section: Resultsmentioning

confidence: 99%

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Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations

et al. 2022

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Biomolecular condensates form via coupled associative and segregative phase transitions of multivalent associative macromolecules. Phase separation coupled to percolation is one example of such transitions. Here, we characterize molecular and mesoscale structural descriptions of condensates formed by intrinsically disordered prion-like low complexity domains (PLCDs). These systems conform to sticker-and-spacers architectures. Stickers are cohesive motifs that drive associative interactions through reversible crosslinking and spacers affect the cooperativity of crosslinking and overall macromolecular solubility. Our computations reproduce experimentally measured sequence-specific phase behaviors of PLCDs. Within simulated condensates, networks of reversible inter-sticker crosslinks organize PLCDs into small-world topologies. The overall dimensions of PLCDs vary with spatial location, being most expanded at and preferring to be oriented perpendicular to the interface. Our results demonstrate that even simple condensates with one type of macromolecule feature inhomogeneous spatial organizations of molecules and interfacial features that likely prime them for biochemical activity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations

et al. 2022

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“…[41][42][43][44] Computational modelling has also been used to study the phase behaviour of FUS. [43,[45][46][47][48][49][50] But models that are sufficiently complex to be biologically relevant suffer from a common limitationtheir parameter space is huge because many properties of the constituent molecules might a priori be important for their behaviour. [51] A popular conceptual model for IDPs is the socalled stickers and spacers model, in which the molecules are regarded as semi-flexible polymers with multiple attractive domains (stickers) connected by weakly-interacting linkers (spacers).…”

Section: Introductionmentioning

confidence: 99%

“…We have previously used Dissipative Particle Dynamics (DPD) simulations to explore the phase behaviour and structure of a model biomolecular condensate formed of a single type of IDP modelled on the FUS low-complexity domain (FUS LC). [50,[54][55][56] Here we ask the simplest question related to the response of a biomolecular condensate to its environment: how does its phase behaviour and internal structure respond to the crowding effect of other macromolecules?…”

Section: Introductionmentioning

confidence: 99%

Macromolecular crowding is surprisingly unable to deform the structure of a model biomolecular condensate

Shillcock

Thomas

Ipsen

et al. 2022

Preprint

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The crowded interior of a living cell makes experiments on simpler systems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically disordered proteins into biomolecular condensates, which is proposed to underlie the membraneless compartmentalisation of many cellular functions. How a cell reliably controls biochemical reactions in compartments open to the compositionally varying cytoplasm is an important question for understanding cellular homeostasis. Computer simulations are often used to study the phase behaviour of model biomolecular condensates, but the number of relevant parameters explodes as the number of protein components increases. It is unfeasible to exhaustively simulate such models for all parameter combinations, although interesting phenomena are almost certainly hidden in the jungle of their high dimensional parameter space. Here we have studied the phase behaviour of a model biomolecular condensate in the presence of a polymeric crowding agent. We used a novel compute framework to execute dozens of simultaneous simulations spanning the protein crowder concentration space. We then combined the results into a graphical representation for human interpretation, which provided an efficient way to search the high-dimensional parameter space. We found that steric repulsion from the crowder drives a near-critical system across the phase boundary, but the molecular arrangement within the resulting biomolecular condensate is rather insensitive to the crowder concentration and molecular weight. We propose that a cell may use the local cytoplasmic concentration to assist formation of biomolecular condensates, while relying on the dense phase reliably providing a stable, structured, fluid milieu for cellular biochemistry despite being open to its changing environment.

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A Versatile Approach to Stabilize Liquid–Liquid Interfaces using Surfactant Self‐Assembly

Honaryar,

Amirfattahi,

Nguyen

et al. 2024

Small

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Stabilizing liquid–liquid interfaces, whether between miscible or immiscible liquids, is crucial for a wide range of applications, including energy storage, microreactors, and biomimetic structures. In this study, a versatile approach for stabilizing the water‐oil interface is presented using the morphological transitions that occur during the self‐assembly of anionic, cationic, and nonionic surfactants mixed with fatty acid oils. The morphological transitions underlying this approach are characterized and extensively studied through small‐angle X‐ray scattering (SAXS), rheometry, and microscopy techniques. Dissipative particle dynamics (DPD) as a simulation tool is adopted to investigate these morphological transitions both in the equilibrium ternary system as well as in the dynamic condition of the water‐oil interface. Such a versatile strategy holds promise for enhancing applications such as liquid‐in‐liquid 3D printing. Moreover, it has the potential to revolutionize a wide range of fields where stabilizing liquid–liquid interfaces not only offers unprecedented opportunities for fine‐tuning nanostructural morphologies but also imparts interesting practical features to the resulting liquid shapes. These features include perfusion capabilities, self‐healing, and porosity, which could have significant implications for various industries.

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Model biomolecular condensates have heterogeneous structure quantitatively dependent on the interaction profile of their constituent macromolecules

Abstract: Model biomolecular condensates have heterogeneous material properties that are tuned by the number and distribution of their constituent proteins’ sticky binding sites.

Cited by 16 publications

References 147 publications

Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations

Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations

Macromolecular crowding is surprisingly unable to deform the structure of a model biomolecular condensate

A Versatile Approach to Stabilize Liquid–Liquid Interfaces using Surfactant Self‐Assembly

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