CReaNet will develop biocompatible Chemical Reaction Networks (CRNs) for signal amplification and novel (bio)materials.

CRNs are ubiquitous in biochemical systems and serve a range of complex biological functions such as signalling (e.g., switching, signal propagation, and amplification), protein synthesis, and homeostasis.[1] Such CRNs operate necessarily in dissipative non-equilibrium states and are orchestrated by feedback loops (i.e., detailed balance cannot exist)[2]. CRNs are often sustained by the consumption of chemical energy (e.g., ATP or GTP hydrolysis) dissipated in the form of heat, and have non-zero (cycle) fluxes. Since CRNs operate far-from-equilibrium, they can give rise to instabilities that result in complex emergent behaviour such as oscillations, multistability, ultrasensitivity, amplification, excitability, quorum sensing, and pattern formation. Much progress has been made since the 1950s on non-linear chemical dynamics (e.g., Bray reaction or Belousov-Zhabotinsky oscillations/spirals/waves) both experimentally and by developing mathematical models.[3] Many of these experimental systems, however, rely on harsh chemical conditions or toxic components and are therefore more difficult to interface with (bio)materials or real-life applications. In biology, the last decades have seen a surge in systems biology, and the consequent unravelling of biological functions and how they are implemented inside the cell in the form of CRNs. More recently, a bottom-up approach is ongoing in the field of synthetic biology, where minimal functions are being reproduced in vitro using CRNs consisting of natural building blocks (e.g., enzymatic DNA oscillators, or trypsin oscillators).[4]

CReaNet takes a different approach in that biocompatible CRNs will be developed with tuneable positive / negative feedback mechanisms that allow the desired function (e.g., oscillation) to be programmed a priori. The tremendous benefit of using programmable and biocompatible CRNs is that they can easily be interfaced with other biological processes and other materials. This approach will provide the design tools to develop novel and improved (bio)materials, with unprecedented functionalities (note: research in materials is one of the key enabling technologies as identified by the EU) [5] Moreover, CRN-based dynamic, autonomous and programmable materials, such as the ones we will describe here, and their control using external stimuli are at the forefront of research in nanoscience and technology.[6]

[1] S. Choi, Systems Biology for Signaling Networks, Springer Science 2010; B. Alberts, Molecular biology of the cell, Garland NY 1994.

[2] H. Qian, J. Phys. Chem. B 2006, 110, 15063-15074.

[3] I. R. Epstein, J. A. Pojman, An introduction to nonlinear chemical dynamics: oscillations, waves, patterns, and chaos, Oxford press 1998.

[4] H. W. H. van Roekel, et al. Chem. Soc. Rev. 2015, 44, 7465-7483.