helixCAM: A platform for programmable cellular assembly in bacteria and human cells.

Area of Science:

• Synthetic biology
• Biomaterials engineering
• Cellular engineering

Background:

• Precise control over cell-cell interactions is crucial for tissue engineering, signaling pathway elucidation, and immune cell targeting.
• Naturally occurring cell adhesion molecules (CAMs) often exhibit cross-reactivity and are endogenously expressed, limiting their programmability for specific interactions.

Purpose of the Study:

• To develop a platform for engineering synthetic cell adhesion molecules (CAMs) for precise, programmable cell-cell interactions.
• To demonstrate the utility of synthetic CAMs for multicellular engineering applications.

Main Methods:

• Developed the helixCAM platform, which presents coiled-coil peptides on the cell surface to mediate synthetic cell-cell adhesion.
• Designed and screened helixCAM libraries based on coiled-coil interaction principles to identify high-performance pairs.
• Applied helixCAMs in bacterial and human cell systems to engineer specific interactions and patterned structures.

Main Results:

• Successfully created specific cell-cell interactions and directed patterned aggregate formation using helixCAMs in both bacteria and human cells.
• Discovered novel, high-performance helixCAM pairs through rational library design.
• Demonstrated diverse multicellular engineering applications including spherical layering, adherent cell targeting, and surface patterning.

Conclusions:

• The helixCAM platform provides a powerful tool for engineering synthetic cell-cell interactions with high specificity.
• HelixCAMs enable precise control over cellular organization and behavior, opening new avenues for tissue engineering and targeted therapies.