Abstract

The ability of cells to sense and respond to their environment is encoded in biomolecular reaction networks, in which information travels through processes such as production, modification, and removal of biomolecules. Recent advances in biotechnology have made it possible to reengineer these physical processes to the point where synthetic biomolecular circuits can be inserted into cells to program cell behavior for useful functionalities. These circuits are often designed in a bottom-up fashion with smaller components connected to form complex systems. In a bottom-up approach to design, it is highly desirable that circuit components behave modularly, that is, the input-output behavior of a module characterized in isolation remains unchanged when the context changes. Unfortunately, due to the physical processes by which information is communicated from one biomolecular circuit module to the other, the lack of modularity is often a problem. In fact, the input-output behavior of a module depends on both direct connectivity to other modules, due to loading effects, and indirect connectivity arising from loads applied to shared cellular resources. In this paper, we summarize the published work illustrating how the means of molecular communication lead to these problems. Specifically, we review the concept of retroactivity, which has been proposed to capture loading problems within a “signals and systems” framework, allowing for engineering solutions that restore modularity.

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