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Title: Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters

Abstract

Inorganic polyphosphate (polyP) is an often-overlooked biopolymer of phosphate residues present in living cells. PolyP is associated with many essential biological roles. Despite interest in polyP’s function, most studies have been limited to extracellular or isolated protein experiments, as polyanionic polyP does not traverse the nonpolar membrane of cells. To address this problem, we developed a robust, readily employed method for polyP delivery using guanidinium-rich oligocarbonate transporters that electrostatically complex polyPs of multiple lengths, forming discrete nanoparticles that are resistant to phosphatase degradation and that readily enter multiple cell types. Fluorescently labeled polyPs have been monitored over time for subcellular localization and release from the transporter, with control over release rates achieved by modulating the transporter identity and the charge ratio of the electrostatic complexes. Furthermore, this general approach to polyP delivery enables the study of intracellular polyP signaling in a variety of applications.

Authors:
ORCiD logo [1];  [1];  [1]; ORCiD logo [2]; ORCiD logo [1]; ORCiD logo [1]
  1. Stanford Univ., Stanford, CA (United States)
  2. Albert-Ludwigs Univ., Freiburg (Germany)
Publication Date:
Research Org.:
Leland Stanford Junior Univ., Palo Alto, CA (United States); Stanford Univ., CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1474016
Alternate Identifier(s):
OSTI ID: 1483936; OSTI ID: 1508740
Grant/Contract Number:  
SC0018168
Resource Type:
Journal Article: Published Article
Journal Name:
ACS Central Science
Additional Journal Information:
Journal Volume: 4; Journal Issue: 10; Journal ID: ISSN 2374-7943
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Fernandes-Cunha, Gabriella M., McKinlay, Colin J., Vargas, Jessica R., Jessen, Henning J., Waymouth, Robert M., and Wender, Paul A. Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters. United States: N. p., 2018. Web. doi:10.1021/acscentsci.8b00470.
Fernandes-Cunha, Gabriella M., McKinlay, Colin J., Vargas, Jessica R., Jessen, Henning J., Waymouth, Robert M., & Wender, Paul A. Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters. United States. doi:10.1021/acscentsci.8b00470.
Fernandes-Cunha, Gabriella M., McKinlay, Colin J., Vargas, Jessica R., Jessen, Henning J., Waymouth, Robert M., and Wender, Paul A. Wed . "Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters". United States. doi:10.1021/acscentsci.8b00470.
@article{osti_1474016,
title = {Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters},
author = {Fernandes-Cunha, Gabriella M. and McKinlay, Colin J. and Vargas, Jessica R. and Jessen, Henning J. and Waymouth, Robert M. and Wender, Paul A.},
abstractNote = {Inorganic polyphosphate (polyP) is an often-overlooked biopolymer of phosphate residues present in living cells. PolyP is associated with many essential biological roles. Despite interest in polyP’s function, most studies have been limited to extracellular or isolated protein experiments, as polyanionic polyP does not traverse the nonpolar membrane of cells. To address this problem, we developed a robust, readily employed method for polyP delivery using guanidinium-rich oligocarbonate transporters that electrostatically complex polyPs of multiple lengths, forming discrete nanoparticles that are resistant to phosphatase degradation and that readily enter multiple cell types. Fluorescently labeled polyPs have been monitored over time for subcellular localization and release from the transporter, with control over release rates achieved by modulating the transporter identity and the charge ratio of the electrostatic complexes. Furthermore, this general approach to polyP delivery enables the study of intracellular polyP signaling in a variety of applications.},
doi = {10.1021/acscentsci.8b00470},
journal = {ACS Central Science},
issn = {2374-7943},
number = 10,
volume = 4,
place = {United States},
year = {2018},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1021/acscentsci.8b00470

Citation Metrics:
Cited by: 1 work
Citation information provided by
Web of Science

Figures / Tables:

Figure 1 Figure 1: Oligocarbonate transporters and FITC-labeled cargo used for the evaluation of polyP delivery. (A) Synthesis of fluorescently tagged polyP-FITC conjugates by phosphoramidate end-labeling. (B) Previously reported oligocarbonate molecular transporters used for siRNA and InsP7 delivery.

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Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.