Designer membraneless organelles sequester native factors for control of cell behavior

Garabedian, Mikael V.; Wang, Wentao; Dabdoub, Jorge B.; Tong, Michelle; Caldwell, Reese M.; Benman, William; Schuster, Benjamin S.; Deiters, Alexander; Good, Matthew C.

doi:10.1038/s41589-021-00840-4

Title: Designer membraneless organelles sequester native factors for control of cell behavior

Journal Article · 01 August 2021 · Nature Chemical Biology

DOI: https://doi.org/10.1038/s41589-021-00840-4 · OSTI ID:1991581

^[1]; Wang, Wentao ^[2]; Dabdoub, Jorge B. ^[2]; Tong, Michelle ^[2]; Caldwell, Reese M. ^[2]; Benman, William ^[2];

^[3];

^[4];

^[2]

Univ. of Pennsylvania, Philadelphia, PA (United States); University of Pennsylvania
Univ. of Pennsylvania, Philadelphia, PA (United States)
Rutgers Univ., Piscataway, NJ (United States)
Univ. of Pittsburgh, PA (United States)

Subcellular compartmentalization of macromolecules increases flux and prevents inhibitory interactions to control biochemical reactions. Inspired by this functionality, we sought to build designer compartments that function as hubs to regulate the flow of information through cellular control systems. Here we report a synthetic membraneless organelle platform to control endogenous cellular activities through sequestration and insulation of native proteins. We engineer and express a disordered protein scaffold to assemble micron size condensates and recruit endogenous clients via genomic tagging with high-affinity dimerization motifs. By relocalizing up to ninety percent of a targeted enzymes to synthetic condensates, we efficiently control cellular behaviors, including proliferation, division, and cytoskeletal organization. Further, we demonstrate multiple strategies for controlled cargo release from condensates to switch cells between functional states. These synthetic organelles offer a powerful and generalizable approach to modularly control cell decision-making in a variety of model systems with broad applications for cellular engineering.

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Research Organization:: Univ. of Pennsylvania, Philadelphia, PA (United States)

Sponsoring Organization:: National Institute of Biomedical Imaging and Bioengineering; National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0007063

OSTI ID:: 1991581

Journal Information:: Nature Chemical Biology, Journal Name: Nature Chemical Biology Journal Issue: 9 Vol. 17; ISSN 1552-4450

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
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Title: Designer membraneless organelles sequester native factors for control of cell behavior

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References (57)

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