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

View ORCID ProfileGeorge Chao, View ORCID ProfileTimothy M. Wannier, View ORCID ProfileClair Travis, View ORCID ProfileNathaniel C. Borders, View ORCID ProfileEvan Appleton, View ORCID ProfileAnjali Chadha, View ORCID ProfileTina Lebar, View ORCID ProfileGeorge M. Church
doi: https://doi.org/10.1101/2022.04.19.488034
George Chao
1Genetics Department, Harvard Medical School. Boston, Massachusetts. USA
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  • For correspondence: gchao@hms.harvard.edu gchurch@genetics.med.harvard.edu
Timothy M. Wannier
1Genetics Department, Harvard Medical School. Boston, Massachusetts. USA
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Clair Travis
2Department of Chemistry, Massachusetts Institute of Technology. Cambridge, MA. USA
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Nathaniel C. Borders
1Genetics Department, Harvard Medical School. Boston, Massachusetts. USA
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Evan Appleton
1Genetics Department, Harvard Medical School. Boston, Massachusetts. USA
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Anjali Chadha
3Department of Bioengineering, Massachusetts Institute of Technology. Cambridge, MA. USA
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Tina Lebar
4Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA. USA
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George M. Church
1Genetics Department, Harvard Medical School. Boston, Massachusetts. USA
4Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA. USA
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  • For correspondence: gchao@hms.harvard.edu gchurch@genetics.med.harvard.edu
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Summary

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 its utility in tissue engineering, immunology, and developmental biology.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 19, 2022.
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helixCAM: A Platform for Programmable Cellular Assembly in Bacteria and Human Cells
George Chao, Timothy M. Wannier, Clair Travis, Nathaniel C. Borders, Evan Appleton, Anjali Chadha, Tina Lebar, George M. Church
bioRxiv 2022.04.19.488034; doi: https://doi.org/10.1101/2022.04.19.488034
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helixCAM: A Platform for Programmable Cellular Assembly in Bacteria and Human Cells
George Chao, Timothy M. Wannier, Clair Travis, Nathaniel C. Borders, Evan Appleton, Anjali Chadha, Tina Lebar, George M. Church
bioRxiv 2022.04.19.488034; doi: https://doi.org/10.1101/2022.04.19.488034

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