Affinity between Macromolecular Regulators Leads to Precise Control of Liquid-Liquid Phase Separation

et al. 2021

Sci Rep

Biomolecular condensates are liquid-like membraneless compartments that contribute to the spatiotemporal organization of proteins, RNA, and other biomolecules inside cells. Some membraneless compartments, such as nucleoli, are dispersed as different condensates that do not grow beyond a certain size, or do not present coalescence over time. In this work, using a minimal protein model, we show that phase separation of binary mixtures of scaffolds and low-valency clients that can act as surfactants—i.e., that significantly reduce the droplet surface tension—can yield either a single drop or multiple droplets that conserve their sizes on long timescales (herein ‘multidroplet size-conserved’ scenario’), depending on the scaffold to client ratio. Our simulations demonstrate that protein connectivity and condensate surface tension regulate the balance between these two scenarios. The multidroplet size-conserved scenario spontaneously arises at increasing surfactant-to-scaffold concentrations, when the interfacial penalty for creating small liquid droplets is sufficiently reduced by the surfactant proteins that are preferentially located at the interface. In contrast, low surfactant-to-scaffold concentrations enable continuous growth and fusion of droplets without restrictions. Overall, our work proposes one thermodynamic mechanism to help rationalize how size-conserved coexisting condensates can persist inside cells—shedding light on the roles of protein connectivity, binding affinity, and droplet composition in this process.

Section: Resultsmentioning

confidence: 99%

Size conservation emerges spontaneously in biomolecular condensates formed by scaffolds and surfactant clients

et al. 2021

Sci Rep

“…The presence of surfactant clients within the condensate substantially lowers the liquid network connectivity 62,82,83 , and therefore, reduces the enthalpic gain sustaining LLPS. Consequently, the system minimizes its free energy by optimizing the number of surfactants that are incorporated into the bulk condensed phase; i.e., by creating higher surface/volume ratios, where surfactants are preferentially located towards the interface rather than in the core.…”

Section: Box Geometrymentioning

confidence: 99%

Size Conservation Emerges Spontaneously in Biomolecular Condensates Formed by Scaffolds and Surfactant Clients

et al. 2021

Preprint

Biomolecular condensates are liquid-like membraneless compartments that contribute to the spatiotemporal organization of proteins, RNA, and other biomolecules inside cells. Some membraneless compartments, such as nucleoli, are dispersed as different condensates that do not grow beyond a certain size, or do not present coalescence over time. In this work, using a minimal protein model, we show that phase separation of binary mixtures of scaffolds and low-valency clients that can act as surfactants—i.e., that significantly reduce the droplet surface tension—can yield either a single drop or multiple droplets that conserve their sizes on long timescales (herein ‘multidroplet size-conserved’), depending on the scaffold to client ratio. Our simulations demonstrate that protein connectivity and condensate surface tension regulate the balance between these two scenarios. Multidroplet size-conserved behavior spontaneously arises at increasing surfactant-to-scaffold concentrations, when the interfacial penalty for creating small liquid droplets is sufficiently reduced by the surfactant proteins that are preferentially located at the interface. In contrast, low surfactant-to-scaffold concentrations enable continuous growth and fusion of droplets without restrictions. Overall, our work proposes one potential thermodynamic mechanism to help rationalize how size-conserved coexisting condensates can persist inside cells—shedding light on the roles of general biomolecular features such as protein connectivity, binding affinity, and droplet composition in this process.

Size conservation emerges spontaneously in biomolecular condensates formed by scaffolds and surfactant clients

et al. 2021

Preprint

Biomolecular condensates are liquid-like membraneless compartments that contribute to the spatiotemporal organization of proteins, RNA, and other biomolecules inside cells. Some membraneless compartments, such as nucleoli, are dispersed as different condensates that do not grow beyond a certain size, or do not present coalescence over time. In this work, using a minimal protein model, we show that phase separation of binary mixtures of scaffolds and low-valency clients that can act as surfactants—i.e., that significantly reduce the droplet surface tension—can yield either a single drop or multiple droplets that conserve their sizes on long timescales (herein ‘multidroplet size-conserved’), depending on the scaffold to client ratio. Our simulations demonstrate that protein connectivity and condensate surface tension regulate the balance between these two scenarios. Multidroplet size-conserved behavior spontaneously arises at increasing surfactant-to-scaffold concentrations, when the interfacial penalty for creating small liquid droplets is sufficiently reduced by the surfactant proteins that are preferentially located at the interface. In contrast, low surfactant-to-scaffold concentrations enable continuous growth and fusion of droplets without restrictions. Overall, our work proposes one potential thermodynamic mechanism to help rationalize how size-conserved coexisting condensates can persist inside cells—shedding light on the roles of general biomolecular features such as protein connectivity, binding affinity, and droplet composition in this process.