Engineering Reversible Cell-Cell Interactions with Lipid Anchored Prosthetic Receptors

Area of Science:

• Biotechnology
• Cell Biology
• Materials Science

Background:

• Genetically engineered receptors have limitations in cell type applicability and permanence.
• Developing non-genetic methods for cell surface modification is crucial for broader applications.

Purpose of the Study:

• To develop a rapid, stable, and reversible non-genetic method for engineering cell membranes with prosthetic receptors.
• To demonstrate the utility of chemically self-assembled nanorings (CSANs) for targeted cell-cell interactions.

Main Methods:

• Installation of bifunctional CSANs displaying EpCAM-targeted fibronectin domains onto cell membranes via hydrophobic insertion.
• Assessment of CSAN stability on cell membranes.
• Evaluation of CSAN-labeled cell recognition of EpCAM-expressing target cells and reversibility of interactions using trimethoprim.

Main Results:

• CSANs were stably bound to cell membranes for over 72 hours in vitro.
• CSAN-labeled cells successfully recognized and formed interactions with EpCAM-expressing target cells.
• Intercellular interactions were effectively reversed by trimethoprim-induced nanoring disassembly.

Conclusions:

• The CSAN system provides a versatile, non-genetic approach to engineer cell surfaces with prosthetic receptors.
• This method enables specific and reversible control over cell-cell interactions.
• The technology holds potential for both scientific tools and clinical therapeutics.