Finite-state automata (FSA) are simple computational devices that can nevertheless illustrate interesting behaviours. We propose that FSA can be employed as control circuits for engineered stochastic biological and biomolecular systems. We present an implementation of FSA using counts of chemical species in the range of hundreds to thousands, which is relevant for the counts of many key molecules such as mRNAs in prokaryotic cells. The challenge here is to ensure a robust representation of the current state in the face of stochastic noise. We achieve this by using a multistable approximate majority algorithm to stabilize and store the current state of the system. Arbitrary finite state machines can thus be compiled into robust stochastic chemical automata. We present two variants: one that consumes its input signals to initiate state transitions and one that does not. We characterize the state change dynamics of these systems and demonstrate their application to solve the four-bit binary square root problem. Our work lays the foundation for the use of chemical automata as control circuits in bioengineered systems and biorobotics.
Adapting one’s behavior to environmental conditions and past experience is a key trait of living systems. In the biological world, there is evidence for adaptive behaviors such as learning even in naturally occurring, non-neural, single-celled organisms. In the bioengineered world, advances in synthetic cell engineering and biorobotics have created the possibility of implementing lifelike systems engineered from the bottom up. This will require the development of programmable control circuitry for such biomimetic systems that is capable of realizing such non-trivial and adaptive behavior, including modification of subsequent behavior in response to environmental feedback. To this end, we report the design of novel stochastic chemical reaction networks capable of probabilistic decision-making in response to stimuli. We show that a simple chemical reaction network motif can be tuned to produce arbitrary decision probabilities when choosing between two or more responses to a stimulus signal. We further show that simple feedback mechanisms from the environment can modify these probabilities over time, enabling the system to adapt its behavior dynamically in response to positive or negative reinforcement based on its decisions. This system thus acts as a form of operant conditioning of the chemical circuit, in the sense that feedback provided based on decisions taken by the circuit form the basis of the learning process. Our work thus demonstrates that simple chemical systems can be used to implement lifelike behavior in engineered biomimetic systems.
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