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 journalArticle

6 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1291-1301
Number of pages11
JournalBioconjugate Chemistry
Volume29
Issue number4
DOIs
StatePublished - Apr 18 2018

Fingerprint

Nanorings
Cell Engineering
Cell membranes
Prosthetics
Cell Communication
Lipids
Cell adhesion
Cell Adhesion Molecules
Artificial Receptors
Cell Membrane
Trimethoprim
Molecules
Antibiotics
Antigens
Fibronectins
Ligands
Anti-Bacterial Agents
Engineers
Epithelial Cells

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

Cite this

Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors. / Csizmar, Clifford M.; Petersburg, Jacob R.; Hendricks, Alex; Stern, Lawrence A.; Hackel, Benjamin J; Wagner, Carston R.

In: Bioconjugate Chemistry, Vol. 29, No. 4, 18.04.2018, p. 1291-1301.

Research output: Contribution to journalArticle

Csizmar, Clifford M. ; Petersburg, Jacob R. ; Hendricks, Alex ; Stern, Lawrence A. ; Hackel, Benjamin J ; Wagner, Carston R. / Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors. In: Bioconjugate Chemistry. 2018 ; Vol. 29, No. 4. pp. 1291-1301.
@article{a9feb64f3af24afc8257a60270114076,
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.",
author = "Csizmar, {Clifford M.} and Petersburg, {Jacob R.} and Alex Hendricks and Stern, {Lawrence A.} and Hackel, {Benjamin J} and Wagner, {Carston R}",
year = "2018",
month = "4",
day = "18",
doi = "10.1021/acs.bioconjchem.8b00058",
language = "English (US)",
volume = "29",
pages = "1291--1301",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors

AU - Csizmar, Clifford M.

AU - Petersburg, Jacob R.

AU - Hendricks, Alex

AU - Stern, Lawrence A.

AU - Hackel, Benjamin J

AU - Wagner, Carston R

PY - 2018/4/18

Y1 - 2018/4/18

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85045555233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045555233&partnerID=8YFLogxK

U2 - 10.1021/acs.bioconjchem.8b00058

DO - 10.1021/acs.bioconjchem.8b00058

M3 - Article

VL - 29

SP - 1291

EP - 1301

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 4

ER -