4-bit adhesion logic enables universal multicellular interface patterning.

Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions 1,2 . The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning 3,4 . Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems 5-8 . 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 5,7,10-13 . 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. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. 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 5-8,14 . 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 .