helixCAM: A Platform for Programmable Cellular Assembly in Bacteria and Human Cells

• Published in: bioRxiv
• Main Authors: Chao, George, Wannier, Timothy M, Clair, Travis, Borders, Nathaniel C, Appleton, Evan, Chadha, Anjali, Lebar, Tina, Church, George M
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 20.04.2022
• Subjects: Cell adhesion molecules; Cell interactions; Cell surface; Cross-reactivity; Developmental biology; Engineering; Pattern formation; Tissue engineering
• DOI: 10.1101/2022.04.19.488034

Interactions between cells are indispensable for creating structure and signaling. The ability to direct precise cell-cell interactions would be powerful for engineering tissues, understanding signaling pathways, and directing immune cell targeting. In humans, intercellular interactions are mediated by cell adhesion molecules (CAMs). However, CAMs are natively expressed by many cells and have cross-reactivity, making them unsuitable for programming specific interactions. Here, we showcase "helixCAM," a platform for engineering novel CAMs by presenting coiled-coil peptides on the cell surface. helixCAMs were able to create specific cell-cell interactions and direct patterned aggregate formation in bacteria and human cells. We built rationally designed helixCAM libraries and discovered novel high-performance helixCAM pairs. High-affinity helixCAMs were then used for multicellular engineering applications, such as spherical layering, adherent cell targeting, and surface patterning. The helixCAMs are an expandable platform for directing complex multicellular assemblies, and we foresee their utility in tissue engineering, immunology, and developmental biology. Competing Interest Statement The authors have declared no competing interest. Footnotes * Misplaced Figure 6/Missing Figure 7