Micropatterned DNA hydrogels for spatiotemporal programming of chemical reaction networks

Abstract

Cells in living systems communicate by sending and receiving signal molecules to coordinate their behavior. To achieve long-distance and noise-resistant communication, cells pattern themselves into spatially organized structures. Inspired by this strategy, systems biology and materials science have aimed to construct artificial communication systems whose dynamics can be controlled by their spatial arrangement. However, experimental understanding of how spatial arrangement influences communication remains limited, mainly due to the difficulty of precisely positioning multiple artificial cellular agents. Here, we demonstrate that communication between artificial cell-like units can be programmed using DNA-based reaction networks and tuned by their spatial arrangement. Arrays of DNA-functionalized hydrogel posts were fabricated as artificial cellular units using a microscale 3D printing technique, enabling precise and flexible control over their geometry and arrangement. The communication between the posts and the collective behavior of the array can be rationally programmed by implementing DNA-based chemical reaction networks. The arrays can sense locally added DNA stimuli and exhibit transient activation patterns that are unique to input positions. This concept is further extended to post-to-post communication, where catalytic signal amplification in a spatially separated configuration leads to spatially biased activation. Finally, by introducing a negative feedback loop between two post types, we achieve more complex spatiotemporal dynamics in which the collective behavior is strongly influenced by spatial arrangement. Our system provides a simple yet versatile experimental platform for exploring arrangement-governed communication among artificial cellular agents and offers insights into the design of functional systems empowered by collective chemical intelligence.