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      Phase transitions and size scaling of membrane-less organelles

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      The Journal of Cell Biology
      The Rockefeller University Press

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          Abstract

          The coordinated growth of cells and their organelles is a fundamental and poorly understood problem, with implications for processes ranging from embryonic development to oncogenesis. Recent experiments have shed light on the cell size–dependent assembly of membrane-less cytoplasmic and nucleoplasmic structures, including ribonucleoprotein (RNP) granules and other intracellular bodies. Many of these structures behave as condensed liquid-like phases of the cytoplasm/nucleoplasm. The phase transitions that appear to govern their assembly exhibit an intrinsic dependence on cell size, and may explain the size scaling reported for a number of structures. This size scaling could, in turn, play a role in cell growth and size control.

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          Most cited references37

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          Systematic identification of pathways that couple cell growth and division in yeast.

          Size homeostasis in budding yeast requires that cells grow to a critical size before commitment to division in the late prereplicative growth phase of the cell cycle, an event termed Start. We determined cell size distributions for the complete set of approximately 6000 Saccharomyces cerevisiae gene deletion strains and identified approximately 500 abnormally small (whi) or large (lge) mutants. Genetic analysis revealed a complex network of newly found factors that govern critical cell size at Start, the most potent of which were Sfp1, Sch9, Cdh1, Prs3, and Whi5. Ribosome biogenesis is intimately linked to cell size through Sfp1, a transcription factor that controls the expression of at least 60 genes implicated in ribosome assembly. Cell growth and division appear to be coupled by multiple conserved mechanisms.
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            Getting RNA and protein in phase.

            Nonmembrane-bound organelles such as RNA granules behave like dynamic droplets, but the molecular details of their assembly are poorly understood. Several recent papers identify structural features that drive granule assembly, shedding light on how phase transitions functionally organize the cell and may lead to pathological protein aggregation. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Peptide-nucleotide microdroplets as a step towards a membrane-free protocell model.

              Although phospholipid bilayers are ubiquitous in modern cells, their impermeability, lack of dynamic properties, and synthetic complexity are difficult to reconcile with plausible pathways of proto-metabolism, growth and division. Here, we present an alternative membrane-free model, which demonstrates that low-molecular-weight mononucleotides and simple cationic peptides spontaneously accumulate in water into microdroplets that are stable to changes in temperature and salt concentration, undergo pH-induced cycles of growth and decay, and promote α-helical peptide secondary structure. Moreover, the microdroplets selectively sequester porphyrins, inorganic nanoparticles and enzymes to generate supramolecular stacked arrays of light-harvesting molecules, nanoparticle-mediated oxidase activity, and enhanced rates of glucose phosphorylation, respectively. Taken together, our results suggest that peptide-nucleotide microdroplets can be considered as a new type of protocell model that could be used to develop novel bioreactors, primitive artificial cells and plausible pathways to prebiotic organization before the emergence of lipid-based compartmentalization on the early Earth.
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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                23 December 2013
                : 203
                : 6
                : 875-881
                Affiliations
                Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544
                Author notes
                Correspondence to Clifford P. Brangwynne: cbrangwy@ 123456princeton.edu
                Article
                201308087
                10.1083/jcb.201308087
                3871435
                24368804
                4a8208a5-e941-4897-ac25-5279975f176c
                © 2013 Brangwynne

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 15 August 2013
                : 27 November 2013
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                Cell biology
                Cell biology

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