Periodic Reporting for period 2 - CReaNet (Chemical Reaction Networks: signal amplification, spatiotemporal control, and materials)
Reporting period: 2021-04-01 to 2023-09-30
CRNs are ubiquitous in nature to control signaling, protein synthesis, and homeostasis. CReaNet developed (biocompatible) CRNs with tuneable feedback mechanisms resulting in life-like functions.
We developed CRNs in homogeneous environments (WP1), controlling spatiotemporal behaviour (WP2), and integrating them into materials (WP3). Key findings were artificial microtubules, and so-called "shunts" in CRNs, similar to ones that regulate respiration and metabolism. In order to get spatiotemporal control we developed on-chip coupled reactors or connected liposomes. In fluidic chips, we have seen propagation of waves akin signalling waves and patterns that are ubiquitous in nature. Lastly, we have developed a number of novel (bio)materials with life-like functions.
Importantly, this project has trained 15 researchers with intricate knowledge of CRNs and coupling to fluidics/materials that are moving to careers in industry and academia, continuing to pioneer applications in a chemical, biological, or forensic setting.
We developed CRNs in homogeneous environments (WP1), controlling spatiotemporal behaviour (WP2), and integrating them into materials (WP3). Key findings were artificial microtubules, and so-called "shunts" in CRNs, similar to ones that regulate respiration and metabolism. In order to get spatiotemporal control we developed on-chip coupled reactors or connected liposomes. In fluidic chips, we have seen propagation of waves akin signalling waves and patterns that are ubiquitous in nature. Lastly, we have developed a number of novel (bio)materials with life-like functions.
Importantly, this project has trained 15 researchers with intricate knowledge of CRNs and coupling to fluidics/materials that are moving to careers in industry and academia, continuing to pioneer applications in a chemical, biological, or forensic setting.
The ESRs recruited in this project worked a range of topics and subprojects related to (biocompatible) CRNs. This resulted in 20 peer-reviewed publication in leading scientific journals, such as Advanced Materials, J. Am. Chem. Soc., Lab-on-a-chip, and others. Related to WP1, the team from the Netherlands (Technical University Delft) used a CRN to detect small amounts of thiols through signal amplification. By also including disulfide cross-links, they could also use this approach to physically degrade hydrogel materials on demand. The same team also developed CRNs based on beta-substituted Michael acceptors and for on-demand release of secondary amines. In a collaboration, with the team at the University of Strasbourg, one of the first examples of artificial CRNs containing shunts (i.e. shortcuts) was demonstrated, which serves as an exemplary approach for other CRNs that are being developed world-wide. In WP2, a number of novel approaches were developed to obtain spatiotemporal control over CRNs. The Swedish team demonstrated a number of approaches to allow growth and fusion on membrane networks. Such artificial networks consisting of membranes are ideally suited to obtain more life-like environments of artificial CRNs, even leading to colony-like protocell superstructures as shown by the same team recently. The team in Mainz (Germany) used feedback and communication to grow hydrogel structures, resulting in a new way to compartimentalize CRNs, leading to interesting feedback mechanisms. In WP3, a number of transient materials and systems were developed. Such approaches lead to time-programmable formation of complex supramolecular or colloidal assemblies, which can possibly used in future medical treatments, such as short-term artery clamping. The Strasbourg team developed a comprehensive model to describe chemically fuelled supramolecular polymerization, which further helps the community to design and use CRNs to control (bio-)materials. As an interesting application, the Mainz team showed how CRNs can be used to make autonomous soft robots that can bend materials, interlock multiple gel components transiently, and even pick up underwater objects using transient gel expansion/contraction. Overall, CReanet has provided deep new insights in how to design, make, control, and understand CRNs, which thoroughly impacted the communities of Systems Chemistry, Supramolecular Chemistry, and Biomaterials. By demonstrating new types of chemistry, complex CRN topologies, and control over their spatiotemporal behaviour, we enabled life-like materials that can perform advanced tasks like seen in the natural world. Overall, thousands of scientists, members of the general public, and policy makers were reached through the dissemination activities, scientific publications, and presentations across Europe and beyond.
This European Training Network (ETN) entitled “Chemical Reaction Networks: Signal amplification, spatiotemporal control, and materials” (CReaNet) has trained bright early-stage researchers (ESRs) on the emerging topic of chemical reaction networks (CRNs). Six excellent academic research groups and four award-winning non-academic beneficiaries have prepared the students using a training-through-research philosophy, and made sure they acquired intersectoral (i.e. academic and industrial) experience. Physical Chemistry, Biochemistry, Physics, and Engineering are all of key importance in CReaNet, guaranteeing a highly multidisciplinary education of our ESRs.
CReaNet has strengthened Europe’s innovation capacity by establishing a critical mass of scientists in an emerging area of research with knowledge currently scattered across Europe. The Network brought together a team of people with diverse expertise united under the common, strategically relevant technology theme of chemical reaction networks. Despite the diversity, their research interests overlap to allow for productive collaborations and synergy, which is required for the challenges of the proposed research. The Network has a broad scope and ambitious goals; hence, previously non-interacting partners have been included to elevate the research in this field to the next level, and define the state of the art. The Network united leading EU scientists in the fields of (bio)chemistry, biophysics, nanoscience, analytical theory, and microfluidics who have the goal to push the boundaries of the current state-of-the-art, and in this process teach their approaches, methods, and reflections to the ESRs, involve them actively, and provide them with a challenging atmosphere.
Soon, 15 highly trained scientists with a thorough training in systems thinking will spread out over Europe, and are sure to create economic impact in the industry jobs they (will) occupy. More specifically, non-linear CRNs can generate oscillations that can control the temporal control of molecules like drugs and hormones, enabling temporal release of these species. This could enable future implanted medical devices benign to human body. Also, soft materials could be able to contract and expand periodically just by adding chemical fuels, which can lead to a small-scale pump useful for medical or microfluidic purposes. Likewise, assembled molecular machines will be able to operate in a synchronized way to exert macroscopic movement, which can be useful in soft robotics. Since these devices will have components and mechanisms similar to biology, which is an epitome of sustainable system, they could enable more sustainable and environmentally friendly technologies in future.
CReanet helps to improve the understanding of complex systems’ behaviours in various fields. The general public has a basic understanding of causality, where they think that the magnitude of the cause and effect are similar. In complex systems, however, small causes can have large effects (i.e. amplification), and the effect can have a feedback mechanism which affects the cause, leading to emergent dynamics such as oscillations and chaos. These insights can lead to better prediction and control of various chemical systems, ranging from chemical plants to intracellular environment. This insight is not limited to chemical systems, and can improve decision making in various sectors including business and politics, because systems involved in these sectors such as consumer behaviours and global climate also involve feedback mechanisms.
CReaNet has strengthened Europe’s innovation capacity by establishing a critical mass of scientists in an emerging area of research with knowledge currently scattered across Europe. The Network brought together a team of people with diverse expertise united under the common, strategically relevant technology theme of chemical reaction networks. Despite the diversity, their research interests overlap to allow for productive collaborations and synergy, which is required for the challenges of the proposed research. The Network has a broad scope and ambitious goals; hence, previously non-interacting partners have been included to elevate the research in this field to the next level, and define the state of the art. The Network united leading EU scientists in the fields of (bio)chemistry, biophysics, nanoscience, analytical theory, and microfluidics who have the goal to push the boundaries of the current state-of-the-art, and in this process teach their approaches, methods, and reflections to the ESRs, involve them actively, and provide them with a challenging atmosphere.
Soon, 15 highly trained scientists with a thorough training in systems thinking will spread out over Europe, and are sure to create economic impact in the industry jobs they (will) occupy. More specifically, non-linear CRNs can generate oscillations that can control the temporal control of molecules like drugs and hormones, enabling temporal release of these species. This could enable future implanted medical devices benign to human body. Also, soft materials could be able to contract and expand periodically just by adding chemical fuels, which can lead to a small-scale pump useful for medical or microfluidic purposes. Likewise, assembled molecular machines will be able to operate in a synchronized way to exert macroscopic movement, which can be useful in soft robotics. Since these devices will have components and mechanisms similar to biology, which is an epitome of sustainable system, they could enable more sustainable and environmentally friendly technologies in future.
CReanet helps to improve the understanding of complex systems’ behaviours in various fields. The general public has a basic understanding of causality, where they think that the magnitude of the cause and effect are similar. In complex systems, however, small causes can have large effects (i.e. amplification), and the effect can have a feedback mechanism which affects the cause, leading to emergent dynamics such as oscillations and chaos. These insights can lead to better prediction and control of various chemical systems, ranging from chemical plants to intracellular environment. This insight is not limited to chemical systems, and can improve decision making in various sectors including business and politics, because systems involved in these sectors such as consumer behaviours and global climate also involve feedback mechanisms.