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Macromolecular Crowding as an Intracellular Stimulus for Responsive Nanomaterials

Estabrook, Daniel A. and Chapman, John O. and Yen, Shuo-Ting and Lin, Helen H. and Ng, Ethan T. and Zhu, Linglan and van de Wouw, Heidi L. and Campàs, Otger and Sletten, Ellen M. (2022) Macromolecular Crowding as an Intracellular Stimulus for Responsive Nanomaterials. Journal of the American Chemical Society, 144 (37). pp. 16792-16798. ISSN 0002-7863. doi:10.1021/jacs.2c03064.

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Stimuli-responsive materials are exploited in biological, materials, and sensing applications. We introduce a new endogenous stimulus, biomacromolecule crowding, which we achieve by leveraging changes in thermoresponsive properties of polymers upon high concentrations of crowding agents. We prepare poly(2-oxazoline) amphiphiles that exhibit lower critical solution temperatures (LCST) in serum above physiological temperature. These amphiphiles stabilize oil-in-water nanoemulsions at temperatures below the LCST but are ineffective surfactants above the LCST, resulting in emulsion fusion. We find that the transformations observed upon heating nanoemulsions above their surfactant’s LCST can instead be induced at physiological temperatures through the addition of polymers and protein, rendering thermoresponsive materials “crowding responsive.” We demonstrate that the cytosol is a stimulus for nanoemulsions, with droplet fusion occurring upon injection into cells of living zebrafish embryos. This report sets the stage for classes of thermoresponsive materials to respond to macromolecule concentration rather than temperature changes.

Item Type:Article
Related URLs:
URLURL TypeDescription
Estabrook, Daniel A.0000-0001-7237-6291
Chapman, John O.0000-0001-5252-0962
Yen, Shuo-Ting0000-0003-4277-1965
van de Wouw, Heidi L.0000-0002-2115-6325
Sletten, Ellen M.0000-0002-0049-7278
Additional Information:Funding was provided by the following grants to E.M.S.: University of California Cancer Research Coordinating Committee (CNR-18-524809), NIGMS (R01GM135380), American Chemical Society Petroleum Research Fund (57379-DNI4), Alfred P. Sloan Award (FG-2018-10855), and Hellman Fellows Award. D.A.E. was supported by T32 training grants from the National Institutes of Health (5T32GM067555-12), the Dissertation Year Fellowship, and the Majeti-Alapati Fellowship. NMR data were obtained on instruments funded by the National Science Foundation (MRI CHE-1048804). The authors thank the Garcia-Garibay group for the use of equipment, and Edris A. Rivera for training and assistance with heat-stage microscopy. They thank Irene Lim for the synthesis of 6 and 7 and Rachael A. Day for early in cellulo work and project insights. They thank David Goodsell for inspiring the cell illustrations within the graphical abstract and Figure 1. This manuscript is adapted from chapter 5 of D.A.E.’s dissertation.
Funding AgencyGrant Number
University of California Cancer Research Coordinating CommitteeCNR-18-524809
American Chemical Society Petroleum Research Fund57379-DNI4
Alfred P. Sloan FoundationFG-2018-10855
Hellman FellowshipUNSPECIFIED
Dissertation Year FellowshipUNSPECIFIED
Majeti-Alapati FellowshipUNSPECIFIED
Issue or Number:37
Record Number:CaltechAUTHORS:20220922-931611600.10
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117113
Deposited By: Melissa Ray
Deposited On:30 Sep 2022 16:02
Last Modified:30 Sep 2022 16:02

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