Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors

Clifford M. Csizmar; Jacob R. Petersburg; Alex Hendricks; Lawrence A. Stern; Benjamin J Hackel; Carston R Wagner

doi:10.1021/acs.bioconjchem.8b00058

Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors

Clifford M. Csizmar, Jacob R. Petersburg, Alex Hendricks, Lawrence A. Stern, Benjamin J Hackel, Carston R Wagner

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Membrane-engineered cells displaying antigen-targeting ligands are useful as both scientific tools and clinical therapeutics. While genetically encoded artificial receptors have proven efficacious, their scope remains limited, as this approach is not amenable to all cell types and the modification is often permanent. Our group has developed a nongenetic method to rapidly, stably, and reversibly modify any cell membrane with a chemically self-assembled nanoring (CSAN) that can function as a prosthetic receptor. Bifunctional CSANs displaying epithelial cell adhesion molecule (EpCAM)-targeted fibronectin domains were installed on the cell membrane through hydrophobic insertion and remained stably bound for ≥72 h in vitro. These CSAN-labeled cells were capable of recognizing EpCAM-expressing target cells, forming intercellular interactions that were subsequently reversed by disassembling the nanoring with the FDA-approved antibiotic, trimethoprim. This study demonstrates the use of this system to engineer cell surfaces with prosthetic receptors capable of directing specific and reversible cell-cell interactions.

Original language	English (US)
Pages (from-to)	1291-1301
Number of pages	11
Journal	Bioconjugate Chemistry
Volume	29
Issue number	4
DOIs	https://doi.org/10.1021/acs.bioconjchem.8b00058
State	Published - Apr 18 2018

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health R21 CA185627 (CRW), F30 CA210345 (CMC), T32 GM008244 (CMC), R21 EB019518 (BJH), and the University of Minnesota. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. The authors gratefully acknowledge Dr. Bob Hafner (Characterization Facility, University of Minnesota) for his assistance with the transmission electron microscopy experiments. Microscopy work was performed in the University Imaging Center at the University of Minnesota.

Funding Information:
This work was supported by the National Institutes of Health R21 CA185627 (CRW), F30 CA210345 (CMC), T32 GM008244 (CMC), R21 EB019518 (BJH), and the University of Minnesota. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. The authors gratefully acknowledge Dr. Bob Hafner (Characterization Facility University of Minnesota) for his assistance with the transmission electron microscopy experiments. Microscopy work was performed in the University Imaging Center at the University of Minnesota.

Publisher Copyright:
© 2018 American Chemical Society.

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title = "Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors",

abstract = "Membrane-engineered cells displaying antigen-targeting ligands are useful as both scientific tools and clinical therapeutics. While genetically encoded artificial receptors have proven efficacious, their scope remains limited, as this approach is not amenable to all cell types and the modification is often permanent. Our group has developed a nongenetic method to rapidly, stably, and reversibly modify any cell membrane with a chemically self-assembled nanoring (CSAN) that can function as a prosthetic receptor. Bifunctional CSANs displaying epithelial cell adhesion molecule (EpCAM)-targeted fibronectin domains were installed on the cell membrane through hydrophobic insertion and remained stably bound for ≥72 h in vitro. These CSAN-labeled cells were capable of recognizing EpCAM-expressing target cells, forming intercellular interactions that were subsequently reversed by disassembling the nanoring with the FDA-approved antibiotic, trimethoprim. This study demonstrates the use of this system to engineer cell surfaces with prosthetic receptors capable of directing specific and reversible cell-cell interactions.",

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note = "Funding Information: This work was supported by the National Institutes of Health R21 CA185627 (CRW), F30 CA210345 (CMC), T32 GM008244 (CMC), R21 EB019518 (BJH), and the University of Minnesota. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. The authors gratefully acknowledge Dr. Bob Hafner (Characterization Facility, University of Minnesota) for his assistance with the transmission electron microscopy experiments. Microscopy work was performed in the University Imaging Center at the University of Minnesota. Funding Information: This work was supported by the National Institutes of Health R21 CA185627 (CRW), F30 CA210345 (CMC), T32 GM008244 (CMC), R21 EB019518 (BJH), and the University of Minnesota. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. The authors gratefully acknowledge Dr. Bob Hafner (Characterization Facility University of Minnesota) for his assistance with the transmission electron microscopy experiments. Microscopy work was performed in the University Imaging Center at the University of Minnesota. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

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AU - Hackel, Benjamin J

AU - Wagner, Carston R

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N2 - Membrane-engineered cells displaying antigen-targeting ligands are useful as both scientific tools and clinical therapeutics. While genetically encoded artificial receptors have proven efficacious, their scope remains limited, as this approach is not amenable to all cell types and the modification is often permanent. Our group has developed a nongenetic method to rapidly, stably, and reversibly modify any cell membrane with a chemically self-assembled nanoring (CSAN) that can function as a prosthetic receptor. Bifunctional CSANs displaying epithelial cell adhesion molecule (EpCAM)-targeted fibronectin domains were installed on the cell membrane through hydrophobic insertion and remained stably bound for ≥72 h in vitro. These CSAN-labeled cells were capable of recognizing EpCAM-expressing target cells, forming intercellular interactions that were subsequently reversed by disassembling the nanoring with the FDA-approved antibiotic, trimethoprim. This study demonstrates the use of this system to engineer cell surfaces with prosthetic receptors capable of directing specific and reversible cell-cell interactions.

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Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors

Abstract

Bibliographical note

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Nikon Inverted TI-E Deconvolution Microscope

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Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors

Abstract

Bibliographical note

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Nikon Inverted TI-E Deconvolution Microscope

University Imaging Centers

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