Issue 31, 2024

Effects of charge asymmetry on the liquid–liquid phase separation of polyampholytes and their condensate properties

Abstract

Liquid–liquid phase separation (LLPS) is the mechanism underlying the formation of bio-molecular condensates which are important compartments regulating intra- and extra-cellular functions. Electrostatic interactions are some of the important driving forces of the LLPS behaviors of biomolecules. However, the understanding of the electrostatic interactions is still limited, especially in the mixtures of biomolecules with different charge patterns. Here, we focus on the electrostatic interactions in mixtures of charge-asymmetric and charge-symmetric polyampholytes and their roles in the phase separation behaviors. We build charge-asymmetric and charge-symmetric model proteins consisting of both glutamic acid (E, negatively charged) and lysine (K, positively charged), i.e. polyampholytes of E35K15 (charge asymmetric) and E25K25 (charge symmetric). Pure E25K25 can undergo LLPS. To investigate the effects of charge-asymmetric polyampholytes on the mixtures of E25K25/E35K15, we perform coarse-grained simulations to determine their phase separation. The charge-asymmetric polyampholyte E35K15 is resistant to the LLPS of the mixtures of E25K25/E35K15. The condensate density decreases with the molar fraction of E35K15 increasing to 0.4, and no LLPS occurs at the molar fraction of 0.5 and above. This can be attributed to the electrostatic repulsion between the negatively charged E35K15 polymers. We further investigate the effects of charge asymmetry on the conformations and properties of the condensates. The E35K15 polymers in the condensates exhibit a more collapsed state as the molar fraction of E35K15 increases. However, the conformation of E25K25 polymers changes slightly across different condensates. The surface tensions of condensates decline with the increase of the molar fraction of E35K15 polymers, while the diffusivity of polymers in the condensed phases is enhanced. This work elucidates the role of charge-asymmetric polyampholytes in determining the LLPS behaviours of binary mixtures of charge-symmetric and charge-asymmetric proteins as well as the properties of condensed phases.

Graphical abstract: Effects of charge asymmetry on the liquid–liquid phase separation of polyampholytes and their condensate properties

Supplementary files

Article information

Article type
Paper
Submitted
03 May 2024
Accepted
11 Jul 2024
First published
12 Jul 2024

Soft Matter, 2024,20, 6150-6159

Effects of charge asymmetry on the liquid–liquid phase separation of polyampholytes and their condensate properties

Y. An, T. Gao, T. Wang, D. Zhang and B. Bharti, Soft Matter, 2024, 20, 6150 DOI: 10.1039/D4SM00532E

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