Dehydration entropy drives liquid-liquid phase separation by molecular crowding

Sohee Park; Ryan Barnes; Yanxian Lin; Byoung jin Jeon; Saeed Najafi; Kris T. Delaney; Glenn H. Fredrickson; Joan Emma Shea; Dong Soo Hwang; Songi Han

doi:10.1038/s42004-020-0328-8

Dehydration entropy drives liquid-liquid phase separation by molecular crowding

Sohee Park, Ryan Barnes, Yanxian Lin, Byoung jin Jeon, Saeed Najafi, Kris T. Delaney, Glenn H. Fredrickson, Joan Emma Shea, Dong Soo Hwang^*, Songi Han^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

Abstract

Complex coacervation driven liquid-liquid phase separation (LLPS) of biopolymers has been attracting attention as a novel phase in living cells. Studies of LLPS in this context are typically of proteins harboring chemical and structural complexity, leaving unclear which properties are fundamental to complex coacervation versus protein-specific. This study focuses on the role of polyethylene glycol (PEG)—a widely used molecular crowder—in LLPS. Significantly, entropy-driven LLPS is recapitulated with charged polymers lacking hydrophobicity and sequence complexity, and its propensity dramatically enhanced by PEG. Experimental and field-theoretic simulation results are consistent with PEG driving LLPS by dehydration of polymers, and show that PEG exerts its effect without partitioning into the dense coacervate phase. It is then up to biology to impose additional variations of functional significance to the LLPS of biological systems.

Original language	English (US)
Article number	83
Journal	Communications Chemistry
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42004-020-0328-8
State	Published - Dec 1 2020

Funding

The work of B.-j.J. was supported by the U.S. Department of Energy (DOE), Office of Science, Basic Energy Sciences (BES), under Award # DESC0014427. D.S.H. was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M1A5A1027592, NRF-2016M1A5A1027594, and NRF-2017R1A2B3006354). Support for the ODNP studies was provided by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2033— Project number 390677874. Studies of LLPS by S.H. and J.-E.S. were supported by the National Institutes of Health (NIH) under Grant Number R01AG05605, while computational method development for CC by J.-E.S. and G.H.F. was supported by the MRSEC Program of the National Science Foundation under Award No. DMR 1720256. J.-E.S. acknowledges support from the National Science Foundation NSF under Award No. MCB-1716956 for the CC simulations. FTS used resources of the Extreme Science and Engineering Discovery Environment (XSEDE, supported by the NSF Project TG-MCA05S027) and the Center for Scientific Computing from the California NanoSystems Institute UC Santa Barbara (CNSI) available through the Materials Research Laboratory (MRL): an NSF MRSEC (DMR-1720256) and NSF CNS-1725797.

ASJC Scopus subject areas

General Chemistry
Environmental Chemistry
Biochemistry
Materials Chemistry

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abstract = "Complex coacervation driven liquid-liquid phase separation (LLPS) of biopolymers has been attracting attention as a novel phase in living cells. Studies of LLPS in this context are typically of proteins harboring chemical and structural complexity, leaving unclear which properties are fundamental to complex coacervation versus protein-specific. This study focuses on the role of polyethylene glycol (PEG)—a widely used molecular crowder—in LLPS. Significantly, entropy-driven LLPS is recapitulated with charged polymers lacking hydrophobicity and sequence complexity, and its propensity dramatically enhanced by PEG. Experimental and field-theoretic simulation results are consistent with PEG driving LLPS by dehydration of polymers, and show that PEG exerts its effect without partitioning into the dense coacervate phase. It is then up to biology to impose additional variations of functional significance to the LLPS of biological systems.",

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AU - Delaney, Kris T.

AU - Fredrickson, Glenn H.

AU - Shea, Joan Emma

AU - Hwang, Dong Soo

AU - Han, Songi

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Dehydration entropy drives liquid-liquid phase separation by molecular crowding

Abstract

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