Progress and limitations in engineering cellular adhesion for research and therapeutics

• Published in: Trends in cell biology 2024-04, Vol.34 (4), p.277-287
• Main Authors: Chao, George, Zukin, Stefan, Fortuna, Patrick R.J., Boettner, Benjamin, Church, George M.
• Format: Article
• Language: English
• Subjects: cellular organization; developmental biology; immunology; membrane protein; organoids; rational design
• ISSN: 0962-8924; 1879-3088
• DOI: 10.1016/j.tcb.2023.07.007

The ability to direct cell–cell interactions through engineered cell adhesion molecules (CAMs) represents an emerging frontier in studying cell biology and in many therapeutic applications.Engineered CAM methods include chemical methods (e.g., click chemistry and single-stranded DNA) as well as protein-based methods (e.g., coiled coils and nanobody–antigen).Whether an engineered CAM system is compatible with a target application requires consideration of both molecular and application-specific characteristics.The number of currently available engineered CAMs only represent a fraction of the quantity and capabilities that can theoretically be achieved.Existing engineered CAMs can already be directly applied to advance research within immunology, developmental biology, organoid, tissue engineering, and neuroscience fields. 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. 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 biolo