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Mol. Cells

Published online December 30, 2021

© The Korean Society for Molecular and Cellular Biology

Rich Phase Separation Behavior of Biomolecules

Yongdae Shin1,2,*

1Department of Mechanical Engineering, Seoul National University, Seoul 08826, Korea, 2Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Korea

Correspondence to : ydshin@snu.ac.kr

Received: August 1, 2021; Revised: September 10, 2021; Accepted: September 10, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Phase separation is a thermodynamic process leading to the formation of compositionally distinct phases. For the past few years, numerous works have shown that biomolecular phase separation serves as biogenesis mechanisms of diverse intracellular condensates, and aberrant phase transitions are associated with disease states such as neurodegenerative diseases and cancers. Condensates exhibit rich phase behaviors including multiphase internal structuring, noise buffering, and compositional tunability. Recent studies have begun to uncover how a network of intermolecular interactions can give rise to various biophysical features of condensates. Here, we review phase behaviors of biomolecules, particularly with regard to regular solution models of binary and ternary mixtures. We discuss how these theoretical frameworks explain many aspects of the assembly, composition, and miscibility of diverse biomolecular phases, and highlight how a model-based approach can help elucidate the detailed thermodynamic principle for multicomponent intracellular phase separation.

Keywords condensate, membrane-less organelle, phase diagram, phase separation, regular solution model

Article

On-line First

Mol. Cells

Published online December 30, 2021

Copyright © The Korean Society for Molecular and Cellular Biology.

Rich Phase Separation Behavior of Biomolecules

Yongdae Shin1,2,*

1Department of Mechanical Engineering, Seoul National University, Seoul 08826, Korea, 2Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Korea

Correspondence to:ydshin@snu.ac.kr

Received: August 1, 2021; Revised: September 10, 2021; Accepted: September 10, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Phase separation is a thermodynamic process leading to the formation of compositionally distinct phases. For the past few years, numerous works have shown that biomolecular phase separation serves as biogenesis mechanisms of diverse intracellular condensates, and aberrant phase transitions are associated with disease states such as neurodegenerative diseases and cancers. Condensates exhibit rich phase behaviors including multiphase internal structuring, noise buffering, and compositional tunability. Recent studies have begun to uncover how a network of intermolecular interactions can give rise to various biophysical features of condensates. Here, we review phase behaviors of biomolecules, particularly with regard to regular solution models of binary and ternary mixtures. We discuss how these theoretical frameworks explain many aspects of the assembly, composition, and miscibility of diverse biomolecular phases, and highlight how a model-based approach can help elucidate the detailed thermodynamic principle for multicomponent intracellular phase separation.

Keywords: condensate, membrane-less organelle, phase diagram, phase separation, regular solution model

Mol. Cells
Dec 31, 2021 Vol.44 No.12, pp. 861~919
COVER PICTURE
Structure of the fly peripheral neurons in the fly head. Flies have basic sensory organs including eyes for vision, antennae and maxillary palps for olfaction, and proboscis (magenta) for gustation which can be labelled with monoclonal antibody 22C10. The figure is a 3D reconstructed image with 30 slices of confocal sections with 3 μm interval. It shows that the proboscis is required for sensing attractive carboxylic acids such as glycolic acid, citric acid, and lactic acid (Shrestha and Lee, pp. 900-910).

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