4-bit adhesion logic enables universal multicellular interface patterning

Abstract

<jats:title>Abstract</jats:title><jats:p>Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions<jats:sup>1,2</jats:sup>. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning<jats:sup>3,4</jats:sup>. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems<jats:sup>5–8</jats:sup>. However, our ability to engineer multicellular interface patterns<jats:sup>2,9</jats:sup> is still very limited, as synthetic cell–cell adhesion toolkits and suitable patterning algorithms are underdeveloped<jats:sup>5,7,10–13</jats:sup>. 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<jats:sup>5–8,14</jats:sup>. 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<jats:sup>3,5</jats:sup>.</jats:p>