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Biomolecules 2019, 9(2), 71; https://doi.org/10.3390/biom9020071

Molecular Crowding Tunes Material States of Ribonucleoprotein Condensates

1
Department of Physics, University at Buffalo, SUNY, NY 14260, USA
2
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Received: 31 December 2018 / Revised: 5 February 2019 / Accepted: 5 February 2019 / Published: 19 February 2019
(This article belongs to the Special Issue Intrinsically Disordered Proteins and Chronic Diseases)
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Abstract

Ribonucleoprotein (RNP) granules are membraneless liquid condensates that dynamically form, dissolve, and mature into a gel-like state in response to a changing cellular environment. RNP condensation is largely governed by promiscuous attractive inter-chain interactions mediated by low-complexity domains (LCDs). Using an archetypal disordered RNP, fused in sarcoma (FUS), here we study how molecular crowding impacts the RNP liquid condensation. We observe that the liquid–liquid coexistence boundary of FUS is lowered by polymer crowders, consistent with an excluded volume model. With increasing bulk crowder concentration, the RNP partition increases and the diffusion rate decreases in the condensed phase. Furthermore, we show that RNP condensates undergo substantial hardening wherein protein-dense droplets transition from viscous fluid to viscoelastic gel-like states in a crowder concentration-dependent manner. Utilizing two distinct LCDs that broadly represent commonly occurring sequence motifs driving RNP phase transitions, we reveal that the impact of crowding is largely independent of LCD charge and sequence patterns. These results are consistent with a thermodynamic model of crowder-mediated depletion interaction, which suggests that inter-RNP attraction is enhanced by molecular crowding. The depletion force is likely to play a key role in tuning the physical properties of RNP condensates within the crowded cellular space. View Full-Text
Keywords: membraneless organelles; optical tweezer; liquid–liquid phase separation; protein diffusion; depletion interaction; entropic force; low-complexity sequences; intrinsically disordered proteins membraneless organelles; optical tweezer; liquid–liquid phase separation; protein diffusion; depletion interaction; entropic force; low-complexity sequences; intrinsically disordered proteins
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kaur, T.; Alshareedah, I.; Wang, W.; Ngo, J.; Moosa, M.M.; Banerjee, P.R. Molecular Crowding Tunes Material States of Ribonucleoprotein Condensates. Biomolecules 2019, 9, 71.

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