Propagating gene expression fronts in a one-dimensional coupled system of artificial cells

Abstract

Living systems employ front propagation and spatiotemporal patterns encoded in biochemical reactions for communication, self-organization and computation 1-4 . Emulating such dynamics in minimal systems is important for understanding physical principles in living cells [5][6][7][8] and in vitro 9-14 . Here, we report a one-dimensional array of DNA compartments in a silicon chip as a coupled system of artificial cells, o ering the means to implement reaction-di usion dynamics by integrated genetic circuits and chip geometry. Using a bistable circuit we programmed a front of protein synthesis propagating in the array as a cascade of signal amplification and short-range di usion. The front velocity is maximal at a saddle-node bifurcation from a bistable regime with travelling fronts to a monostable regime that is spatially homogeneous. Near the bifurcation the system exhibits large variability between compartments, providing a possible mechanism for population diversity. This demonstrates that on-chip integrated gene circuits are dynamical systems driving spatiotemporal patterns, cellular variability and symmetry breaking.Sharp travelling fronts are prevalent in nature and emerge when nonlinear and dispersive effects combine, for example solitary waves in nonlinear optics, fluid convection, and chemical reactions 15 . Biological multicellular systems use travelling fronts of molecular signals as a means for computation and communication over long distances when signalling by diffusion is inefficient. In these systems, cells can be described as autocatalytic units that amplify and transmit signals beyond a threshold. Because signals dissipate in the medium over short distances, long-range information transmission is achieved by consecutive local cell-cell interactions. Signal propagation has been measured over orders of magnitudes in a variety of biological processes, ranging from fast action potentials in neuron networks with typical velocities 16 of v ≈ 10 7 mm h −1 , to slow gene expression fronts in development 3 with v ≈ 0.1 mm h −1 . Although some systems have a linearly unstable initial state, and thus can be treated as Fisher waves 17 , the majority of biological examples require more complex models, including the cable equation and Hodgkin-Huxley model 18 . These systems raise questions concerning the selected speed, bifurcations, fluctuations and stability in parameter space 15 , which are challenging to study in a living organism.Front propagation has been extensively studied in chemical reactions 16,19 and more recently in reconstituted biological systems, including the bacterial cell division network 10 , the Xenopus laevis cell cycle 11 , and RNA (ref. 20) and DNA (ref. 14) catalytic reactions. In the past decade cell-free transcription-translation reactions have been used to advance the design of programmable artificial gene systems, including bulk solution 21 , gels 9 , membrane vesicles 22 , water-in-oil drops 23 , microfluidic devices 24 and on-chip DNA compartments 13 . So far, however, a synthet...

Microscopic agents programmed by DNA circuits

“…Compartments efficiently restrict the diffusion of reactive species 35 , but conversely require specific strategies in order to open communication channels between the units [36][37][38][39] . Living organisms elegantly manage transfer across their boundaries.…”

Short DNA containing χ sites enhances DNA stability and gene expression in E. coli cell‐free transcription–translation systems

“…The cell-free TXTL technology has become versatile enough to be employed for biomanufacturing and medicine (Ng et al 2012; Pardee et al 2016), metabolic engineering (Dudley et al 2014), and quantitative disciplines such as biophysics (Tayar A. 2015).…”

Cell-sized mechanosensitive and biosensing compartment programmed with DNA

“…The new generation of DNA-dependent cell-free transcription-translation systems (TXTL) has been engineered to address applications over a broad spectrum of engineering and fundamental disciplines, from synthetic biology to biophysics and chemistry 2–4 . Modern TXTL platforms are used for medicine and biomolecular manufacturing, such as the production of vaccine and therapeutics 5, 6 .…”