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Optimization and stability of cell–polymer hybrids obtained by “clicking” synthetic polymers to metabolically labeled cell surface glycans
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Tomás, Ruben M. F. and Gibson, Matthew I. (2019) Optimization and stability of cell–polymer hybrids obtained by “clicking” synthetic polymers to metabolically labeled cell surface glycans. Biomacromolecules, 20 (7). pp. 2726-2736. doi:10.1021/acs.biomac.9b00478 ISSN 1525-7797.
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Official URL: https://doi.org/10.1021/acs.biomac.9b00478
Abstract
Re-engineering of mammalian cell surfaces with polymers enables the introduction of functionality including imaging agents, drug cargoes or antibodies for cell-based therapies, without resorting to genetic techniques. Glycan metabolic labeling has been reported as a tool for engineering cell surface glycans with synthetic polymers through the installation of biorthogonal handles, such as azides. Quantitative assessment of this approach and the robustness of the engineered coatings has yet to be explored. Here, we graft poly(hydroxyethyl acrylamide) onto azido-labeled cell surface glycans using strain-promoted azide–alkyne “click” cycloaddition and, using a combination of flow cytometry and confocal microscopy, evaluate the various parameters controlling the outcome of this “grafting to” process. In all cases, homogeneous cell coatings were formed with >95% of the treated cells being covalently modified, superior to nonspecific “grafting to” approaches. Controllable grafting densities could be achieved through modulation of polymer chain length and/or concentration, with longer polymers having lower densities. Cell surface bound polymers were retained for at least 72 h, persisting through several mitotic divisions during this period. Furthermore, we postulate that glycan/membrane recycling is slowed by the steric bulk of the polymers, demonstrating robustness and stability even during normal biological processes. This cytocompatible, versatile and simple approach shows potential for re-engineering of cell surfaces with new functionality for future use in cell tracking or cell-based therapies.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QD Chemistry Q Science > QH Natural history Q Science > QP Physiology Q Science > QR Microbiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||
SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Cell membranes , Glycoconjugates , T cells -- Receptors, Addition polymerization | |||||||||||||||
Journal or Publication Title: | Biomacromolecules | |||||||||||||||
Publisher: | American Chemical Society | |||||||||||||||
ISSN: | 1525-7797 | |||||||||||||||
Official Date: | 29 May 2019 | |||||||||||||||
Dates: |
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Volume: | 20 | |||||||||||||||
Number: | 7 | |||||||||||||||
Page Range: | pp. 2726-2736 | |||||||||||||||
DOI: | 10.1021/acs.biomac.9b00478 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 19 September 2019 | |||||||||||||||
Date of first compliant Open Access: | 23 September 2019 | |||||||||||||||
RIOXX Funder/Project Grant: |
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