Associated Faculty, Chemical and Biological Engineering

Contact

cbrangwy@princeton.edu
609-258-4528
Hoyt Chemical Laboratory, 301
Brangwynne Lab

Research Area

Cell Biology, Development & Cancer

Research Focus

Biophysical approaches to understanding growth of RNA/protein assemblies, cells, and tissues



Research
Selected Publications
We 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.




Lee DSW, Strom AR, Brangwynne CP. The mechanobiology of nuclear phase separation. APL Bioeng. 2022 ;6(2):021503. PubMed
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Gouveia B, Kim Y, Shaevitz JW, Petry S, Stone HA, Brangwynne CP. Capillary forces generated by biomolecular condensates. Nature. 2022 ;609(7926):255-264. PubMed
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Jack A, Kim Y, Strom AR, Lee DSW, Williams B, Schaub JM, et al. Compartmentalization of telomeres through DNA-scaffolded phase separation. Dev Cell. 2022 ;57(2):277-290.e9. PubMed
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Rana U, Brangwynne CP, Panagiotopoulos AZ. Phase separation vs aggregation behavior for model disordered proteins. J Chem Phys. 2021 ;155(12):125101. PubMed
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Zhang Y, Lee DSW, Meir Y, Brangwynne CP, Wingreen NS. Mechanical Frustration of Phase Separation in the Cell Nucleus by Chromatin. Phys Rev Lett. 2021 ;126(25):258102. PubMed
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Shimobayashi SF, Ronceray P, Sanders DW, Haataja MP, Brangwynne CP. Nucleation landscape of biomolecular condensates. Nature. 2021 ;599(7885):503-506. PubMed
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Eeftens JM, Kapoor M, Michieletto D, Brangwynne CP. Polycomb condensates can promote epigenetic marks but are not required for sustained chromatin compaction. Nat Commun. 2021 ;12(1):5888. PubMed
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Safari MS, King MR, Brangwynne CP, Petry S. Interaction of spindle assembly factor TPX2 with importins-α/β inhibits protein phase separation. J Biol Chem. 2021 ;297(3):100998. PubMed
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Strom AR, Biggs RJ, Banigan EJ, Wang X, Chiu K, Herman C, et al. HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics. Elife. 2021 ;10. PubMed
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Sanders DW, Jumper CC, Ackerman PJ, Bracha D, Donlic A, Kim H, et al. SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation. Elife. 2021 ;10. PubMed
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Treen N, Shimobayashi SF, Eeftens J, Brangwynne CP, Levine M. Properties of repression condensates in living Ciona embryos. Nat Commun. 2021 ;12(1):1561. PubMed
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Lafontaine DLJ, Riback JA, Bascetin R, Brangwynne CP. The nucleolus as a multiphase liquid condensate. Nat Rev Mol Cell Biol. 2021 ;22(3):165-182. PubMed
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Esposito M, Fang C, Cook KC, Park N, Wei Y, Spadazzi C, et al. TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis. Nat Cell Biol. 2021 ;23(3):257-267. PubMed
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Statt A, Casademunt H, Brangwynne CP, Panagiotopoulos AZ. Model for disordered proteins with strongly sequence-dependent liquid phase behavior. J Chem Phys. 2020 ;152(7):075101. PubMed
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Wei M-T, Chang Y-C, Shimobayashi SF, Shin Y, Strom AR, Brangwynne CP. Nucleated transcriptional condensates amplify gene expression. Nat Cell Biol. 2020 ;22(10):1187-1196. PubMed
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Riback JA, Zhu L, Ferrolino MC, Tolbert M, Mitrea DM, Sanders DW, et al. Composition-dependent thermodynamics of intracellular phase separation. Nature. 2020 ;581(7807):209-214. PubMed
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Sanders DW, Kedersha N, Lee DSW, Strom AR, Drake V, Riback JA, et al. Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization. Cell. 2020 ;181(2):306-324.e28. PubMed
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Riback JA, Brangwynne CP. Can phase separation buffer cellular noise?. Science. 2020 ;367(6476):364-365. PubMed
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Riback JA, Brangwynne CP. Can phase separation buffer cellular noise?. Science. 2020 ;367(6476):364-365. PubMed
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Riback JA, Brangwynne CP. Can phase separation buffer cellular noise?. Science. 2020 ;367(6476):364-365. PubMed
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Bracha D, Walls MT, Brangwynne CP. Probing and engineering liquid-phase organelles. Nat Biotechnol. 2019 ;37(12):1435-1445. PubMed
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Strom AR, Brangwynne CP. The liquid nucleome - phase transitions in the nucleus at a glance. J Cell Sci. 2019 ;132(22). PubMed
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Taylor NO, Wei M-T, Stone HA, Brangwynne CP. Quantifying Dynamics in Phase-Separated Condensates Using Fluorescence Recovery after Photobleaching. Biophys J. 2019 ;117(7):1285-1300. PubMed
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Zhu L, Richardson TM, Wacheul L, Wei M-T, Feric M, Whitney G, et al. 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. PubMed
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Bracha D, Walls MT, Wei M-T, Zhu L, Kurian M, Avalos JL, et al. Mapping Local and Global Liquid Phase Behavior in Living Cells Using Photo-Oligomerizable Seeds. Cell. 2018 ;175(6):1467-1480.e13. PubMed
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Shin Y, Chang Y-C, Lee DSW, Berry J, Sanders DW, Ronceray P, et al. Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome. Cell. 2018 ;175(6):1481-1491.e13. PubMed
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Dine E, Gil AA, Uribe G, Brangwynne CP, Toettcher JE. Protein Phase Separation Provides Long-Term Memory of Transient Spatial Stimuli. Cell Syst. 2018 ;6(6):655-663.e5. PubMed
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Shin Y, Berry J, Pannucci N, Haataja MP, Toettcher JE, Brangwynne CP. Spatiotemporal Control of Intracellular Phase Transitions Using Light-Activated optoDroplets. Cell. 2017 ;168(1-2):159-171.e14. PubMed
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Wei M-T, Elbaum-Garfinkle S, Holehouse AS, Chen CChih-Hsiun, Feric M, Arnold CB, et al. Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles. Nat Chem. 2017 ;9(11):1118-1125. PubMed
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Shin Y, Brangwynne CP. Liquid phase condensation in cell physiology and disease. Science. 2017 ;357(6357). PubMed
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Sanders DW, Brangwynne CP. Neurodegenerative disease: RNA repeats put a freeze on cells. Nature. 2017 ;546(7657):215-216. PubMed
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Thutupalli S, Uppaluri S, Constable GWA, Levin SA, Stone HA, Tarnita CE, et al. Farming and public goods production in populations. Proc Natl Acad Sci U S A. 2017 ;114(9):2289-2294. PubMed
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Taylor N, Elbaum-Garfinkle S, Vaidya N, Zhang H, Stone HA, Brangwynne CP. Biophysical characterization of organelle-based RNA/protein liquid phases using microfluidics. Soft Matter. 2016 ;12(45):9142-9150. PubMed
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Feric M, Vaidya N, Harmon TS, Mitrea DM, Zhu L, Richardson TM, et al. Coexisting Liquid Phases Underlie Nucleolar Subcompartments. Cell. 2016 ;165(7):1686-1697. PubMed
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Uppaluri S, Weber SC, Brangwynne CP. Hierarchical Size Scaling during Multicellular Growth and Development. Cell Rep. 2016 ;17(2):345-352. PubMed
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Brangwynne CP, Marko JF. Cell division: A sticky problem for chromosomes. Nature. 2016 ;535(7611):234-5. PubMed
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Berry J, Weber SC, Vaidya N, Haataja M, Brangwynne CP. RNA transcription modulates phase transition-driven nuclear body assembly. Proc Natl Acad Sci U S A. 2015 ;112(38):E5237-45. PubMed
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Bosse JB, Hogue IB, Feric M, Thiberge SY, Sodeik B, Brangwynne CP, et al. Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion. Proc Natl Acad Sci U S A. 2015 ;112(42):E5725-33. PubMed
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Zhang H, Elbaum-Garfinkle S, Langdon EM, Taylor N, Occhipinti P, Bridges AA, et al. RNA Controls PolyQ Protein Phase Transitions. Mol Cell. 2015 ;60(2):220-30. PubMed
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Feric M, Broedersz CP, Brangwynne CP. Soft viscoelastic properties of nuclear actin age oocytes due to gravitational creep. Sci Rep. 2015 ;5:16607. PubMed
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Elbaum-Garfinkle S, Brangwynne CP. Liquids, Fibers, and Gels: The Many Phases of Neurodegeneration. Dev Cell. 2015 ;35(5):531-532. PubMed
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Uppaluri S, Brangwynne CP. A size threshold governs Caenorhabditis elegans developmental progression. Proc Biol Sci. 2015 ;282(1813):20151283. PubMed
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