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

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

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