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Dynamics of Aging Biomolecular Condensates

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SPLW03 - Biological condensates: cellular mechanisms governed by phase transitions

Biomolecular condensates that form via phase separation are complex viscoelastic materials whose properties are thought to influence cellular functions and pathology. In this talk, I will present our experimental and computational results from measurements of sequence-encoded and age-dependent material properties of condensates formed by intrinsically disordered prion-like low-complexity domains (PLCDs) [1, 2]. These measurements have revealed that nascent PLCD condensates are viscoelastic Maxwell fluids, and their sequence-specific dynamical moduli are governed by the strengths of inter-chain interactions. Further, PLCD condensates can undergo physical aging that leads to dynamical arrest on sequence-specific timescales. However, the aged PLCD condensates are non-fibrillar, terminally elastic, Kelvin-Voigt solids. The timescales of fluid-to-solid transitions can be controlled by mutations to spacers that weaken the metastability of fluids. Finally, I will discuss the dynamical properties of aging condensates beyond PLCD systems and biological mechanisms that enhance the metastabilities of terminally viscous condensates.    References:

Alshareedah I, Moosa MM, Pham M, Potoyan DA and Banerjee PR (2021) Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides. Nat Commun 12:6620. doi: 10.1038/s41467-021-26733-7

Alshareedah I, Borcherds WM, Cohen SR, Farag M, Singh A, Bremer A, Pappu RV, Mittag T, and Banerjee PR (2023) Sequence-encoded grammars determine material properties and physical aging of protein condensates. bioRxiv. doi: 10.1101/2023.04.06.535902


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