Bottom-up construction of in vitro switchable memories

TLDR

Bistable and switchable reaction networks enable long‑term memory storage in cells, as shown by epigenetic switches that can be flipped by specific stimuli. The study aims to enable detailed investigation of topology‑function relationships in dynamic reaction networks. The authors construct simplified dynamic analogs of reaction networks in vitro within a controlled artificial environment, avoiding in‑vivo genetic rewiring. They successfully assembled DNA‑based dynamic reaction networks that function as a bistable system, a two‑input switchable memory, and a single‑input push‑push memory, demonstrating that modular design can create complex time‑responsive in‑vitro circuits.

Abstract

Reaction networks displaying bistability provide a chemical mechanism for long-term memory storage in cells, as exemplified by many epigenetic switches. These biological systems are not only bistable but switchable, in the sense that they can be flipped from one state to the other by application of specific molecular stimuli. We have reproduced such functions through the rational assembly of dynamic reaction networks based on basic DNA biochemistry. Rather than rewiring genetic systems as synthetic biology does in vivo, our strategy consists of building simplified dynamic analogs in vitro, in an artificial, well-controlled milieu. We report successively a bistable system, a two-input switchable memory element, and a single-input push-push memory circuit. These results suggest that it is possible to build complex time-responsive molecular circuits by following a modular approach to the design of dynamic in vitro behaviors. Our approach thus provides an unmatched opportunity to study topology/function relationships within dynamic reaction networks.