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Abstract 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 .
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Engineered bacterial swarm patterns as spatial records of environmental inputs
A diverse array of bacteria species naturally self-organize into durable macroscale patterns on solid surfaces via swarming motility—a highly coordinated and rapid movement of bacteria powered by flagella. Engineering swarming is an untapped opportunity to increase the scale and robustness of coordinated synthetic microbial systems. Here we engineer Proteus mirabilis, which natively forms centimeter-scale bullseye swarm patterns, to ‘write’ external inputs into visible spatial records. Specifically, we engineer tunable expression of swarming-related genes that modify pattern features, and we develop quantitative approaches to decoding. Next, we develop a dual-input system that modulates two swarming-related genes simultaneously, and we separately show that growing colonies can record dynamic environmental changes. We decode the resulting multicondition patterns with deep classification and segmentation models. Finally, we engineer a strain that records the presence of aqueous copper. This work creates an approach for building macroscale bacterial recorders, expanding the framework for engineering emergent microbial behaviors.
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- Award ID(s):
- 1847356
- PAR ID:
- 10500733
- Publisher / Repository:
- Nature Chemical Biology
- Date Published:
- Journal Name:
- Nature Chemical Biology
- Volume:
- 19
- Issue:
- 7
- ISSN:
- 1552-4450
- Page Range / eLocation ID:
- 878 to 886
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41589-023-01325-2
