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      Micropolarity governs the structural organization of biomolecular condensates

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          Abstract

          Microenvironment is critical to the function of cells and organisms. One example is provided by biomolecular condensates, whose microenvironment can be vastly different from the surrounding cellular environments to engage unique biological functions. How microenvironments of biomolecular condensates affect their structure and function remains unknown. Here, we show that the arrangements and partitioning of biomolecules are dictated by the differences between the micropolarity of each subcompartment. Sufficient difference in micropolarity results in layered structures with the exterior shell presenting a more polar microenvironment than the interior core. Accordingly, micropolarity inversion is accompanied by conversions of the layered structures. These findings demonstrated the central role of the previously overlooked microenvironment in regulating the structural organization and function of membraneless organelles.

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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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            CHARMM36m: an improved force field for folded and intrinsically disordered proteins

            An all-atom protein force field, CHARMM36m, offers improved accuracy for simulating intrinsically disordered peptides and proteins.
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              Liquid phase condensation in cell physiology and disease.

              Phase transitions are ubiquitous in nonliving matter, and recent discoveries have shown that they also play a key role within living cells. Intracellular liquid-liquid phase separation is thought to drive the formation of condensed liquid-like droplets of protein, RNA, and other biomolecules, which form in the absence of a delimiting membrane. Recent studies have elucidated many aspects of the molecular interactions underlying the formation of these remarkable and ubiquitous droplets and the way in which such interactions dictate their material properties, composition, and phase behavior. Here, we review these exciting developments and highlight key remaining challenges, particularly the ability of liquid condensates to both facilitate and respond to biological function and how their metastability may underlie devastating protein aggregation diseases.
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                Author and article information

                Journal
                bioRxiv
                BIORXIV
                bioRxiv
                Cold Spring Harbor Laboratory
                30 March 2023
                : 2023.03.30.534881
                Affiliations
                [1 ]Department of Chemistry, Research Center for Industries of the Future, Westlake University, 600 Dunyu Road, Hangzhou 310030, Zhejiang Province, China; Institute of Natural Sciences, Westlake Institute for Advanced Study; Hangzhou 310030, Zhejiang Province, China
                [2 ]Department of Chemistry, Massachusetts Institute of Technology; Cambridge, MA 02139
                [3 ]CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
                [4 ]Westlake Laboratory of Life Sciences and Biomedicine; Hangzhou 310024, Zhejiang Province, China
                Author notes
                [* ]Corresponding author. zhangxin@ 123456westlake.edu.cn (X.Z.)

                AUTHOR CONTRIBUTIONS:

                S.Y. and X.Z. conceived the project; S.Y., Y.T., C.H., performed experiments; A.P.L performed computational analysis; J.C. assisted with plasmids cloning; F.L. assisted with organic synthesis and characterization; Y.L., B.Z., and X.Z., supervised the project. S.Y. and X.Z. wrote the paper with help from other coauthors.

                Article
                10.1101/2023.03.30.534881
                10081268
                37034692
                81487324-d4c5-4497-a062-ce27831fe170

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

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