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      Self-assembly of stabilized droplets from liquid–liquid phase separation for higher-order structures and functions

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          Abstract

          Dynamic microscale droplets produced by liquid–liquid phase separation (LLPS) have emerged as appealing biomaterials due to their remarkable features. However, the instability of droplets limits the construction of population-level structures with collective behaviors. Here we first provide a brief background of droplets in the context of materials properties. Subsequently, we discuss current strategies for stabilizing droplets including physical separation and chemical modulation. We also discuss the recent development of LLPS droplets for various applications such as synthetic cells and biomedical materials. Finally, we give insights on how stabilized droplets can self-assemble into higher-order structures displaying coordinated functions to fully exploit their potentials in bottom-up synthetic biology and biomedical applications.

          Abstract

          Dynamic microscale droplets produced by liquid–liquid phase separation (LLPS) have emerged as appealing biomaterials, but their instability hinders their assembly into high-order structures with collective behaviors. Here, the authors review current strategies for stabilizing droplets, as well as recent developments in the applications of such LLPS droplets, and provide insights into how stabilized droplets can self-assemble into higher-order structures that display coordinated functions.

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          Most cited references137

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          Biomolecular condensates: organizers of cellular biochemistry

          In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge.
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            Phase separation of signaling molecules promotes T cell receptor signal transduction.

            Activation of various cell surface receptors triggers the reorganization of downstream signaling molecules into micrometer- or submicrometer-sized clusters. However, the functional consequences of such clustering have been unclear. We biochemically reconstituted a 12-component signaling pathway on model membranes, beginning with T cell receptor (TCR) activation and ending with actin assembly. When TCR phosphorylation was triggered, downstream signaling proteins spontaneously separated into liquid-like clusters that promoted signaling outputs both in vitro and in human Jurkat T cells. Reconstituted clusters were enriched in kinases but excluded phosphatases and enhanced actin filament assembly by recruiting and organizing actin regulators. These results demonstrate that protein phase separation can create a distinct physical and biochemical compartment that facilitates signaling.
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              • Article: not found

              Polymer physics of intracellular phase transitions

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                Author and article information

                Contributors
                sjtu1578252@sjtu.edu.cn
                hjdou@sjtu.edu.cn
                s.mann@bristol.ac.uk
                jianwei.li@utu.fi
                Journal
                Commun Chem
                Commun Chem
                Communications Chemistry
                Nature Publishing Group UK (London )
                2399-3669
                9 April 2024
                9 April 2024
                2024
                : 7
                : 79
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, , Shanghai Jiao Tong University, ; Shanghai, 200240 China
                [2 ]Zhangjiang Institute for Advanced Study (ZIAS), Shanghai Jiao Tong University, ( https://ror.org/0220qvk04) 429 Zhangheng Road, Shanghai, 201203 China
                [3 ]MediCity Research Laboratory, University of Turku, ( https://ror.org/05vghhr25) Tykistökatu 6, Turku, 20520 Finland
                [4 ]Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, ( https://ror.org/0524sp257) Bristol, UK
                [5 ]GRID grid.5337.2, ISNI 0000 0004 1936 7603, Max Planck-Bristol Centre for Minimal Biology, School of Chemistry, , University of Bristol, ; Bristol, BS8 1TS UK
                Author information
                http://orcid.org/0000-0001-8963-260X
                http://orcid.org/0009-0001-0963-5737
                http://orcid.org/0000-0001-5850-9174
                http://orcid.org/0000-0003-3012-8964
                http://orcid.org/0000-0002-3682-6934
                Article
                1168
                10.1038/s42004-024-01168-5
                11004187
                38594355
                e70d73ec-d6b0-49bd-a956-49313ab5b6df
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 December 2023
                : 3 April 2024
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100006306, Sigrid Juséliuksen Säätiö (Sigrid Jusélius Foundation);
                Award ID: Senior Researcher Fellowship
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002341, Academy of Finland (Suomen Akatemia);
                Award ID: 355798
                Award Recipient :
                Funded by: the National Key R&D Program of China (2022YFE0100600), the Tracking Program for Professor of Special Appointment (Eastern Scholar) at the Shanghai Institutions of Higher Learning (SHDP201802), Shanghai Jiao Tong University Translation Medicine Cross Research Fund (YG2021QN09)
                Categories
                Review Article
                Custom metadata
                © Springer Nature Limited 2024

                supramolecular chemistry,self-assembly
                supramolecular chemistry, self-assembly

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