c, Six alternating colonies form a hexagonally symmetric interface pattern. b, A visible interface is formed between two colonies with complementary adhesins (Supplementary Video S1). coli seeded on soft agar form macroscopically visible interfaces when expressing complementary pairs from a library of heterophilic synthetic adhesins (Nb2/Ag2 and Nb3/Ag3 corresponding to yellow/blue and green/red, respectively). Despite recent bioengineering advances 5, 7, experimentally feasible algorithms and standardized modules for multicellular interface patterning are limited, in part because the design potential of cell–cell adhesion 5, 7, 10, 11, 12 is underexplored compared with cell–cell signalling 13, 27, 28, 29, 30.Ī, Schematic of the experimental procedure: overnight cultures of swarming E.

Synthetic biology aims to engineer patterned multicellular systems to facilitate applications including programmable biomaterials, artificial tissues and metabolic consortia, and to provide a build-to-understand methodology for natural systems 5, 6, 7, 8. Mathematically, such interface (or boundary) patterns can often be described as tilings or tessellations 20, 21, which elegantly combine generic algorithmic design principles with functional structure and aesthetic appeal, as exemplified by neuronal self-avoidance tilings 22, 23, DNA tiling self-assembly 24, Islamic architecture 25 and the Tetris video game 26. Plants, fungi and animals can establish tissue boundary patterns through developmental programmes using independently evolved yet similar genetic toolkits, organizers and morphogen fields 1, 3, 4, 17, 18, 19. Similar content being viewed by othersīacterial communities can produce multicellular interfaces through cooperation and competition 15, 16. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems 3, 5. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials 5, 6, 7, 8, 14. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields.

Here we introduce a synthetic cell–cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. However, our ability to engineer multicellular interface patterns 2, 9 is still very limited, as synthetic cell–cell adhesion toolkits and suitable patterning algorithms are underdeveloped 5, 7, 10, 11, 12, 13. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems 5, 6, 7, 8. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning 3, 4. Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions 1, 2.

Regular tessellation in nature