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

David S. Glass, Ingmar H. Riedel-Kruse

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


Synthetic multicellular systems hold promise as models for understanding natural development of biofilms and higher organisms and as tools 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 a 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 nanobodies and antigens 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. Compatible with synthetic biology standards, this adhesion toolbox will enable construction of high-level multicellular designs and shed light on the evolutionary transition to multicellularity. The development of a genetically encoded toolkit of surface-bound nanobodies and antigens in E. coli allows for precise manipulation of cell-cell adhesion and rational design of diverse self-assembled multicellular patterns and morphologies.

Original languageEnglish (US)
Pages (from-to)649-658.e16
Issue number3
StatePublished - Jul 26 2018
Externally publishedYes


  • adhesion
  • morphology
  • multicellularity
  • nanobodies
  • patterning
  • self-assembly
  • self-organization
  • synthetic biology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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