Probing and engineering liquid-phase organelles

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Cells compartmentalize their intracellular environment to orchestrate countless simultaneous biochemical processes. Many intracellular tasks rely on membrane-less organelles, multicomponent condensates that assemble by liquid–liquid phase separation. A decade of intensive research has provided a basic understanding of the biomolecular driving forces underlying the form and function of such organelles. Here we review the technologies enabling these developments, along with approaches to designing spatiotemporally actuated organelles based on multivalent low-affinity interactions. With these recent advances, it is now becoming possible both to modulate the properties of native condensates and to engineer entirely new structures, with the potential for widespread biomedical and biotechnological applications.

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Fig. 1: Diversity of condensate forms and functions in living cells.
Fig. 2: Techniques and technologies for interrogating membrane-less organelles.
Fig. 3: Multivalency in native and engineered condensates.
Fig. 4: Applications of engineered condensates.


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We thank members of the Brangwynne laboratory for comments on the manuscript. This work was supported by the Howard Hughes Medical Institute and by grants from the NIH 4D Nucleome Program (U01 DA040601), the Princeton Center for Complex Materials, and an NSF-supported MRSEC (DMR 1420541). D.B. acknowledges support through a Cross-Disciplinary Postdoctoral Fellowship from the Human Frontiers Science Program. M.T.W. is supported by the National Science Foundation Graduate Research Fellowship Program under grant no. DGE-1656466.

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Correspondence to Clifford P. Brangwynne.

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The authors have filed patents on technologies discussed, including the Corelet, CasDrop and optoDroplet systems.

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Bracha, D., Walls, M.T. & Brangwynne, C.P. Probing and engineering liquid-phase organelles. Nat Biotechnol 37, 1435–1445 (2019) doi:10.1038/s41587-019-0341-6

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