4-bit adhesion logic enables universal multicellular interface patterning

• Published in: Nature (London) Vol. 608; no. 7922; pp. 324 - 329
• Main Authors: Kim, Honesty, Skinner, Dominic J., Glass, David S., Hamby, Alexander E., Stuart, Bradey A. R., Dunkel, Jörn, Riedel-Kruse, Ingmar H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.08.2022; Nature Publishing Group
• Subjects: 14/19; 14/35; 14/63; 42/35; 42/44; 631/553/552; 631/57; 639/301/54; Adhesins; Adhesion; Adhesives; Algorithms; Artificial Cells - cytology; Biofilms; Biological evolution; Cell Adhesion; Engineers; Evolution; Gene mapping; Humanities and Social Sciences; Humans; Interfaces; Logic; Microscopy; multidisciplinary; Pattern formation; Prediction models; Science; Science (multidisciplinary); Swarming; Synthetic biology; Synthetic Biology - methods; Tessellation; Tiling; Toolkits
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-022-04944-2

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 . A synthetic cell-cell adhesion logic using swarming E. coli with 4 bits of information is introduced, enabling the programming of interfaces that combine to form universal tessellation patterns over a large scale.