Abstract
We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.
Highlights
Analog Circuits and Biological Systems, Research Lab of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
We focus on the mapping from electronic circuits to molecular circuits, which is most useful in synthetic biology
We summarize by reviewing seven benefits of analog computation in cells, which are important for synthetic biology
Summary
The mRNA transcripts accumulate on the capacitor C (which always has C = 1 [1]) to create VmRNA, the molecular concentration of mRNA.The resistor RmRNA degrades the mRNA such that the synthesis current from the DNA promoter Pact−rep eventually balances the degradation current and VmRNA equilibrates at a steady-state value. The dependent current generator on the right end of figure 1a ‘translates’ VmRNA via ribosomal machinery in the cell to create a synthesis protein current, which accumulates on a capacitor to create Vprot, the molecular concentration. Compact 8-transistor analog circuits, which are current-mode circuit versions of figure 1a, create analogic basis functions that are mathematically exact representations of prior models [21] They match experimental input–output data gathered from non-pathogenic E. coli [21].
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