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      Phase Transitions of Associative Biomacromolecules

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          Abstract

          <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" id="d3282571e99">Multivalent proteins and nucleic acids, collectively referred to as multivalent associative biomacromolecules, provide the driving forces for the formation and compositional regulation of biomolecular condensates. Here, we review the key concepts of phase transitions of aqueous solutions of associative biomacromolecules, specifically proteins that include folded domains and intrinsically disordered regions. The phase transitions of these systems come under the rubric of coupled associative and segregative transitions. The concepts underlying these processes are presented, and their relevance to biomolecular condensates is discussed. </p>

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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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            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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              Liquid-liquid phase separation in biology.

              Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary to understand the consequences of liquid-like states for biological functions.
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                Author and article information

                Contributors
                Journal
                Chemical Reviews
                Chem. Rev.
                American Chemical Society (ACS)
                0009-2665
                1520-6890
                March 07 2023
                Affiliations
                [1 ]Department of Biomedical Engineering, Center for Biomolecular Condensates (CBC), Washington University in St. Louis, St. Louis, Missouri 63130, United States
                [2 ]Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, Missouri 63130, United States
                [3 ]Max Planck Institute of Cell Biology and Genetics, 01307 Dresden, Germany
                Article
                10.1021/acs.chemrev.2c00814
                36881934
                0d332bc3-c239-47cb-92e3-2d99a919ffb4
                © 2023

                https://doi.org/10.15223/policy-029

                https://doi.org/10.15223/policy-037

                https://doi.org/10.15223/policy-045

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