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1. Proximity to criticality predicts surface properties of biomolecular condensates

   Andrew G. T. Pyo, Yaojun Zhang (June 2023, PNAS nexus)

   It has recently become appreciated that cells self-organize their interiors through the formation of biomolecular condensates. These condensates, typically formed through liquid–liquid phase separation of proteins, nucleic acids, and other biopolymers, exhibit reversible assembly/disassembly in response to changing conditions. Condensates play many functional roles, aiding in biochemical reactions, signal transduction, and sequestration of certain components. Ultimately, these functions depend on the physical properties of condensates, which are encoded in the microscopic features of the constituent biomolecules. In general, the mapping from microscopic features to macroscopic properties is complex, but it is known that near a critical point, macroscopic properties follow power laws with only a small number of parameters, making it easier to identify underlying principles. How far does this critical region extend for biomolecular condensates and what principles govern condensate properties in the critical regime? Using coarse-grained molecular-dynamics simulations of a representative class of biomolecular condensates, we found that the critical regime can be wide enough to cover the full physiological range of temperatures. Within this critical regime, we identified that polymer sequence influences surface tension predominately via shifting the critical temperature. Finally, we show that condensate surface tension over a wide range of temperatures can be calculated from the critical temperature and a single measurement of the interface width. 

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2. RNA in formation and regulation of transcriptional condensates

   https://doi.org/10.1261/rna.078997.121  

   Sharp, Phillip A.; Chakraborty, Arup K.; Henninger, Jonathan E.; Young, Richard A. (December 2021, RNA)

   Macroscopic membraneless organelles containing RNA such as the nucleoli, germ granules, and the Cajal body have been known for decades. These biomolecular condensates are liquid-like bodies that can be formed by a phase transition. Recent evidence has revealed the presence of similar microscopic condensates associated with the transcription of genes. This brief article summarizes thoughts about the importance of condensates in the regulation of transcription and how RNA molecules, as components of such condensates, control the synthesis of RNA. Models and experimental data suggest that RNAs from enhancers facilitate the formation of a condensate that stabilizes the binding of transcription factors and accounts for a burst of transcription at the promoter. Termination of this burst is pictured as a nonequilibrium feedback loop where additional RNA destabilizes the condensate. 

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3. Stress-related biomolecular condensates in plants

   https://doi.org/10.1093/plcell/koad127  

   Solis-Miranda, Jorge; Chodasiewicz, Monika; Skirycz, Aleksandra; Fernie, Alisdair R; Moschou, Panagiotis N; Bozhkov, Peter V; Gutierrez-Beltran, Emilio (May 2023, The Plant Cell)

   Abstract Biomolecular condensates are membraneless organelle-like structures that can concentrate molecules and often form through liquid-liquid phase separation. Biomolecular condensate assembly is tightly regulated by developmental and environmental cues. Although research on biomolecular condensates has intensified in the past 10 years, our current understanding of the molecular mechanisms and components underlying their formation remains in its infancy, especially in plants. However, recent studies have shown that the formation of biomolecular condensates may be central to plant acclimation to stress conditions. Here, we describe the mechanism, regulation, and properties of stress-related condensates in plants, focusing on stress granules and processing bodies, two of the most well-characterized biomolecular condensates. In this regard, we showcase the proteomes of stress granules and processing bodies, in an attempt to suggest methods for elucidating the composition and function of biomolecular condensates. Finally, we discuss how biomolecular condensates modulate stress responses and how they might be used as targets for biotechnological efforts to improve stress tolerance. 

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4. Biomolecular condensate drives polymerization and bundling of the bacterial tubulin FtsZ to regulate cell division

   https://doi.org/10.1038/s41467-023-39513-2  

   Ramm, Beatrice; Schumacher, Dominik; Harms, Andrea; Heermann, Tamara; Klos, Philipp; Müller, Franziska; Schwille, Petra; Søgaard-Andersen, Lotte (June 2023, Nature Communications)

   Abstract Cell division is spatiotemporally precisely regulated, but the underlying mechanisms are incompletely understood. In the social bacteriumMyxococcus xanthus, the PomX/PomY/PomZ proteins form a single megadalton-sized complex that directly positions and stimulates cytokinetic ring formation by the tubulin homolog FtsZ. Here, we study the structure and mechanism of this complex in vitro and in vivo. We demonstrate that PomY forms liquid-like biomolecular condensates by phase separation, while PomX self-assembles into filaments generating a single large cellular structure. The PomX structure enriches PomY, thereby guaranteeing the formation of precisely one PomY condensate per cell through surface-assisted condensation. In vitro, PomY condensates selectively enrich FtsZ and nucleate GTP-dependent FtsZ polymerization and bundle FtsZ filaments, suggesting a cell division site positioning mechanism in which the single PomY condensate enriches FtsZ to guide FtsZ-ring formation and division. This mechanism shares features with microtubule nucleation by biomolecular condensates in eukaryotes, supporting this mechanism’s ancient origin. 

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5. Liquid–liquid phase separation within fibrillar networks

   https://doi.org/10.1038/s41467-023-41528-8  

   Liu, Jason X.; Haataja, Mikko P.; Košmrlj, Andrej; Datta, Sujit S.; Arnold, Craig B.; Priestley, Rodney D. (September 2023, Nature Communications)

   Abstract Complex fibrillar networks mediate liquid–liquid phase separation of biomolecular condensates within the cell. Mechanical interactions between these condensates and the surrounding networks are increasingly implicated in the physiology of the condensates and yet, the physical principles underlying phase separation within intracellular media remain poorly understood. Here, we elucidate the dynamics and mechanics of liquid–liquid phase separation within fibrillar networks by condensing oil droplets within biopolymer gels. We find that condensates constrained within the network pore space grow in abrupt temporal bursts. The subsequent restructuring of condensates and concomitant network deformation is contingent on the fracture of network fibrils, which is determined by a competition between condensate capillarity and network strength. As a synthetic analog to intracellular phase separation, these results further our understanding of the mechanical interactions between biomolecular condensates and fibrillar networks in the cell. 

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