Abstract
Cells are complex machines capable of processing information by means of an entangled network of molecular interactions. A crucial component of these decision-making systems is the presence of memory and this is also a specially relevant target of engineered synthetic systems. A classic example of memory devices is a 1-bit memory element known as the flip-flop. Such system can be in principle designed using a single-cell implementation, but a direct mapping between standard circuit design and a living circuit can be cumbersome. Here we present a novel computational implementation of a 1-bit memory device using a reliable multicellular design able to behave as a set-reset flip-flop that could be implemented in yeast cells. The dynamics of the proposed synthetic circuit is investigated with a mathematical model using biologically-meaningful parameters. The circuit is shown to behave as a flip-flop in a wide range of parameter values. The repression strength for the NOT logics is shown to be crucial to obtain a good flip-flop signal. Our model also shows that the circuit can be externally tuned to achieve different memory states and dynamics, such as persistent and transient memory. We have characterized the parameter domains for robust memory storage and retrieval as well as the corresponding time response dynamics.
Highlights
Developing living devices that can perform non-trivial decisions is one of the major challenges of synthetic biology (Purnick and Weiss, 2009)
A different architecture was implemented in yeast (Ajo-Franklin et al, 2007) using a transcriptional positive feedback with sensitivity to cell growth
Memory was sustained by an autoregulatory transcriptional positive feedback
Summary
Developing living devices that can perform non-trivial decisions is one of the major challenges of synthetic biology (Purnick and Weiss, 2009). The qualitative characterization of how a cell might achieve biological memory through its transcriptional circuitry was determined nearly 50 years ago by Monod and Jacob (1961) Despite this early work, the quantitative understanding of these circuits has been achieved recently (Alon, 2006). The quantitative understanding of these circuits has been achieved recently (Alon, 2006) Inspired in this knowledge, synthetic memory devices have been developed at different scales (Burrill and Silver, 2010; Inniss and Silver, 2013) during the last decade. In an early work, Gardner et al (2000), developed a toggle switch in E. coli This system is based on a two mutual repressors architecture having two stable steady states. Other devices have been explored, including conditional memory systems (Fritz et al, 2007), implementations based on the expression of specific recombinases in bacteria (Siuti et al, 2013) or switchable memories using DNA biochemistry in vitro (Padirac et al, 2012; Inniss and Silver, 2013)
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