Progress and limitations in engineering cellular adhesion for research and therapeutics

Trends Cell Biol. 2024 Apr;34(4):277-287. doi: 10.1016/j.tcb.2023.07.007. Epub 2023 Aug 12.

Abstract

Intercellular interactions form the cornerstone of multicellular biology. Despite advances in protein engineering, researchers artificially directing physical cell interactions still rely on endogenous cell adhesion molecules (CAMs) alongside off-target interactions and unintended signaling. Recently, methods for directing cellular interactions have been developed utilizing programmable domains such as coiled coils (CCs), nanobody-antigen, and single-stranded DNA (ssDNA). We first discuss desirable molecular- and systems-level properties in engineered CAMs, using the helixCAM platform as a benchmark. Next, we propose applications for engineered CAMs in immunology, developmental biology, tissue engineering, and neuroscience. Biologists in various fields can readily adapt current engineered CAMs to establish control over cell interactions, and their utilization in basic and translational research will incentivize further expansion in engineered CAM capabilities.

Keywords: cellular organization; developmental biology; immunology; membrane protein; organoids; rational design.

Publication types

  • Review

MeSH terms

  • Cell Adhesion
  • Cell Adhesion Molecules* / metabolism
  • Cell Communication*
  • Humans
  • Signal Transduction

Substances

  • Cell Adhesion Molecules