A Synthetic Cell-Cell Adhesion Toolbox for Programming Multicellular Morphologies and Patterns
46 Pages Posted: 4 Jun 2018 Sneak Peek Status: PublishedMore...
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.
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