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A Synthetic Cell-Cell Adhesion Toolbox for Programming Multicellular Morphologies and Patterns

46 Pages Posted: 4 Jun 2018 Sneak Peek Status: Published

See all articles by David S. Glass

David S. Glass

Stanford University - Department of Bioengineering

Ingmar H. Riedel-Kruse

Stanford University - Department of Bioengineering

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Abstract

Synthetic multicellular systems hold promise for understanding natural development of biofilms and higher organisms, as well as for engineering complex multi-component metabolic pathways and materials. However, such efforts require tools to adhere cells into defined morphologies and patterns, and these tools are currently lacking. Here we report the first 100% genetically encoded synthetic platform for modular cell-cell adhesion in Escherichia coli, which provides control over multicellular self-assembly. Adhesive selectivity is provided by a library of outer membrane-displayed nanobody and antigen peptides with orthogonal intra-library specificities, while affinity is controlled by intrinsic adhesin affinity, competitive inhibition, and inducible expression. We demonstrate the resulting capabilities for quantitative rational design of well-defined morphologies and patterns through homophilic and heterophilic interactions, lattice-like self-assembly, phase separation, differential adhesion, and sequential layering. This adhesion toolbox, compatible with synthetic biology standards, will enable construction of high-level multicellular designs and shed light on the evolutionary transition to multicellularity.

Suggested Citation

Glass, David S. and Riedel-Kruse, Ingmar H., A Synthetic Cell-Cell Adhesion Toolbox for Programming Multicellular Morphologies and Patterns (2018). Available at SSRN: https://ssrn.com/abstract=3188400 or http://dx.doi.org/10.2139/ssrn.3188400
This is a paper under consideration at Cell Press and has not been peer-reviewed.

David S. Glass (Contact Author)

Stanford University - Department of Bioengineering

Stanford, CA 94305
United States

Ingmar H. Riedel-Kruse

Stanford University - Department of Bioengineering ( email )

Stanford, CA 94305
United States

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