Clifford P. Brangwynne

Contact
cbrangwy@princeton.eduResearch Area
Cell Biology, Development & CancerResearch Focus
Biophysical approaches to understanding growth of RNA/protein assemblies, cells, and tissuesWe are interested in understanding the physical principles underlying self-assembly of biological materials, including the cytoskeleton, sub-cellular organelles, cells, and tissues. Our research combines the tools of soft matter physics and molecular cell biology to understand the way in which the properties of biological materials play a role in fundamental biological processes, in particular embryonic development. To address these questions we work with the worm C. elegans, as well as the frog X. Laevis. We aim to ultimately use the understanding gained in these model organisms to develop self-assembling biomaterials for medical applications.
Patterning in Developing Embryos
Tissue patterning in early development is facilitated in part by asymmetric cell divisions, where a cell divides into two daughter cells that may be different in size, contain different molecular components, and ultimately give rise to different tissues in the adult organism. In C. elegans asymmetric divisions establish germ cells that will go on to form the reproductive gonad in the adult organism. As with many organisms, C. elegans germ cells contain RNA and protein rich germ granules ("P-granules") that are thought to play a role in keeping the germ cells in an un-differentiated stem-cell like state. P-granules localize within the cell cytoplasm in a complex process that relies on the formation of intracellular morphogen gradients that control P-granule assembly. The biophysical nature of these gradients, and the mechanism by which they control P granule stability, are still poorly understood.
Physical Properties and Function of RNA/Protein Bodies
Unlike conventional sub-cellular compartments such as vesicles, cells contain many compartments that form in the absence of membranes. These typically consist of assemblies of RNA and proteins, and include many cytoplasmic bodies such as P-granules. There are also many similar bodies within the nucleus, including Cajal bodies and nucleoli. We are interested in how these bodies form, how they carry out their biological functions, and the role their biophysical properties play. Together with the powerful genetics possible in the worm C. elegans, we also work with the large eggs of the frog X. Laevis.
Architecture and Dynamics of the Cytoskeleton
The cytoskeleton is a dynamic network of biopolymer filaments that plays a central role in many fundamental biological processes, including cell migration, cell division, and intracellular transport. We are interested in collective properties of the cytoskeleton, and the way in which these collective properties can function to spatially organize the cytoplasm of developing cells.
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Capillary forces generated by biomolecular condensates. Nature. 2022 ;609(7926):255-264. .
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The mechanobiology of nuclear phase separation. APL Bioeng. 2022 ;6(2):021503. .
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Compartmentalization of telomeres through DNA-scaffolded phase separation. Dev Cell. 2022 ;57(2):277-290.e9. .
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Phase separation vs aggregation behavior for model disordered proteins. J Chem Phys. 2021 ;155(12):125101. .
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Interaction of spindle assembly factor TPX2 with importins-α/β inhibits protein phase separation. J Biol Chem. 2021 ;297(3):100998. .
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Polycomb condensates can promote epigenetic marks but are not required for sustained chromatin compaction. Nat Commun. 2021 ;12(1):5888. .
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Nucleation landscape of biomolecular condensates. Nature. 2021 ;599(7885):503-506. .
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Properties of repression condensates in living Ciona embryos. Nat Commun. 2021 ;12(1):1561. .
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The nucleolus as a multiphase liquid condensate. Nat Rev Mol Cell Biol. 2021 ;22(3):165-182. .
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TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis. Nat Cell Biol. 2021 ;23(3):257-267. .
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Mechanical Frustration of Phase Separation in the Cell Nucleus by Chromatin. Phys Rev Lett. 2021 ;126(25):258102. .
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Nucleated transcriptional condensates amplify gene expression. Nat Cell Biol. 2020 ;22(10):1187-1196. .
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Composition-dependent thermodynamics of intracellular phase separation. Nature. 2020 ;581(7807):209-214. .
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Can phase separation buffer cellular noise?. Science. 2020 ;367(6476):364-365. .
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Model for disordered proteins with strongly sequence-dependent liquid phase behavior. J Chem Phys. 2020 ;152(7):075101. .
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Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization. Cell. 2020 ;181(2):306-324.e28. .
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Can phase separation buffer cellular noise?. Science. 2020 ;367(6476):364-365. .
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Can phase separation buffer cellular noise?. Science. 2020 ;367(6476):364-365. .
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Quantifying Dynamics in Phase-Separated Condensates Using Fluorescence Recovery after Photobleaching. Biophys J. 2019 ;117(7):1285-1300. .
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The liquid nucleome - phase transitions in the nucleus at a glance. J Cell Sci. 2019 ;132(22). .
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Probing and engineering liquid-phase organelles. Nat Biotechnol. 2019 ;37(12):1435-1445. .
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Controlling the material properties and rRNA processing function of the nucleolus using light. Proc Natl Acad Sci U S A. 2019 ;116(35):17330-17335. .
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Mapping Local and Global Liquid Phase Behavior in Living Cells Using Photo-Oligomerizable Seeds. Cell. 2018 ;175(6):1467-1480.e13. .
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Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome. Cell. 2018 ;175(6):1481-1491.e13. .
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Protein Phase Separation Provides Long-Term Memory of Transient Spatial Stimuli. Cell Syst. 2018 ;6(6):655-663.e5. .
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Liquid phase condensation in cell physiology and disease. Science. 2017 ;357(6357). .
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Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles. Nat Chem. 2017 ;9(11):1118-1125. .
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Neurodegenerative disease: RNA repeats put a freeze on cells. Nature. 2017 ;546(7657):215-216. .
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Spatiotemporal Control of Intracellular Phase Transitions Using Light-Activated optoDroplets. Cell. 2017 ;168(1-2):159-171.e14. .
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Farming and public goods production in populations. Proc Natl Acad Sci U S A. 2017 ;114(9):2289-2294. .
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Hierarchical Size Scaling during Multicellular Growth and Development. Cell Rep. 2016 ;17(2):345-352. .
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Biophysical characterization of organelle-based RNA/protein liquid phases using microfluidics. Soft Matter. 2016 ;12(45):9142-9150. .
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Coexisting Liquid Phases Underlie Nucleolar Subcompartments. Cell. 2016 ;165(7):1686-1697. .
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Cell division: A sticky problem for chromosomes. Nature. 2016 ;535(7611):234-5. .
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RNA transcription modulates phase transition-driven nuclear body assembly. Proc Natl Acad Sci U S A. 2015 ;112(38):E5237-45. .
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Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion. Proc Natl Acad Sci U S A. 2015 ;112(42):E5725-33. .
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RNA Controls PolyQ Protein Phase Transitions. Mol Cell. 2015 ;60(2):220-30. .
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Soft viscoelastic properties of nuclear actin age oocytes due to gravitational creep. Sci Rep. 2015 ;5:16607. .
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Liquids, Fibers, and Gels: The Many Phases of Neurodegeneration. Dev Cell. 2015 ;35(5):531-532. .
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A size threshold governs Caenorhabditis elegans developmental progression. Proc Biol Sci. 2015 ;282(1813):20151283. .