Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks

Abstract

A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.Cells live in complex and dynamic environments. They sense and respond to both external environmental cues and to each other through cell-to-cell communication.Adapting to changing environments often requires cells to perform complex information processing, and cells have developed elaborate signaling networks to accomplish this feat. These biochemical networks are ubiquitous in biology, ranging from the quorum-sensing 1 and chemotaxis networks 2 in single-celled organisms to developmental networks in higher organisms 3 . Inspired by both these natural circuits and physical computing devices, synthetic biologists are designing sophisticated synthetic circuits that can perform complicated "computing-like" behaviors. Synthetic biologists have designed gene circuits executing a wide range of functionalities including switches 4 , oscillators 5 , counters 6 , and even cell-to-cell communicators 7 .Despite these successes, many challenges to harnessing the full potential of synthetic biology persist [8][9][10][11][12][13][14][15] . While there are guiding principles to synthetic biology 16 , actual construction of synthetic circuits often proceeds in an ad-hoc manner through a mixture of biological intuition and trial-and-error. Furthermore, the functionality and applicability is limited by a dearth of biological components 17 . For this reason, it would be helpful to identify general principles that can improve the design of synthetic circuits and help guide the search for new biological parts. One promising direction along these lines is recent work examining the relationship between the information processing capabilities of these biochemical networks and their energetic costs (technically this is usually a cost in free energy, but for the sake of brevity we will refer to this as energy). Energetic costs place important constraints on the design of physical computing de...

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