meeting report

SYSTEMS Complexity emerges from chemistry Chemical systems can show complex behaviour that is not seen in individual or reactions. Helena S. Azevedo, Sarah L. Perry, Peter A. Korevaar, and Dibyendu Das report on the emergence of this complex behaviour, which was discussed at the Virtual Symposium on Systems Chemistry

ystems chemistry is a new frontier Systems chemistry in molecular sciences, focusing on (multi-)functional behaviour that S Phenomena emerges from ensembles of molecular 1–6 components . Creating systems of Functional Synthetic/ molecules can establish behaviour that (bio)materials biological goes beyond the sum of the individual Concepts elements — while taking advantage of well-established methods and traditional Active materials Supramolecular Chemical Origin of and motion assembly networks life chemistry approaches for the study of individual molecules and reactions. The Inputs Out-of-equilibrium Compartmentalization most striking example of such emerging processes behaviour is life itself, and unravelling the Self COVID-19 rules involves decreasing the gap between organization interventions ‘dead’ molecules and living matter. While still in its infancy, this exciting challenge has drawn the attention from chemists worldwide, with backgrounds varying from supramolecular chemistry to prebiotic chemistry, , theoretical biology, and soft matter. Virtual Symposium on Systems Chemistry was hosted by Advanced Science Research Center (CUNY) and organized by Gonen Ashkenasy, Rafal Klajn, David Lynn, Sijbren Otto, Rebecca Fig. 1 | Virtual Symposium on Systems Chemistry. The symposium discussed how chemical inputs, Schulman and Rein Ulijn from 18–20 concepts, and phenomena drive the emerging field of systems chemistry. May 2020. The discussions covered how concepts such as supramolecular assembly, out-of-equilibrium, chemical frameworks, actuate muscle-like hydrogels flow between amphiphile source and drain networks, and compartmentalization and direct the differentiation of stem cells at droplets that are in turn kept in position by translate into phenomena that vary from adsorbed protein layers: exemplifying how filaments assembled from said amphiphile. self-organization to motion, functional well-orchestrated motion from molecular Self-organization critically relies on (bio)materials, new insights into the systems emerges into systems with potential the controlled motion of the entities origins of life, and intervention with the catalytic, self-healing, or therapeutic involved. Lauren Zarzar (Pennsylvania SARS-CoV-2 virus responsible for the functions. State University) developed a system of COVID-19 pandemic (the main reason for Another hallmark of life is oil-in-water microdroplets that chased the online format of the symposium, and, self-organization of matter into patterns each other in a predator–prey analogy. This ironically, a supramolecular system that in and structures. Petra Schwille (MPI motion is powered by the free energy of itself has many aspects related to systems Biochemistry) showed the pathways mixing, regulated by a unique chemotactic chemistry) (Fig. 1). underlying the emergence of patterns signalling between the droplets. Daphne The meeting began with Nobel Laureate from the Min protein system that serves to Klotsa (University of North Carolina at Ben Feringa (University of ), localize the cell centre during the division Chapel Hill) used computational simulations who presented the challenge of integrating of E. coli. Reducing the complexity of to demonstrate how swarms of active motion – a hallmark of life – into the system reveals key network motifs matter particles show emergent collective molecular systems. Starting off with the enabling pattern formation; however, behaviour in fluids, directed by many-body photoisomerization of a core double bond at the same time, complexity might be hydrodynamic interactions. Ayusman Sen in a chiral , his group developed key to the robustness of pattern-forming (Pennsylvania State University) showed a motor that operates at the nanoscale but systems in life. In a more synthetic motion on a much smaller scale with produces, by amplification of collective context, Peter Korevaar (Radboud collective behaviour of molecules that molecular motion, motility at much larger University) demonstrated the emergence of could be facilitated by cascade scales. Molecular motors were shown to multi-droplet self-organization at air–water and enzyme proximity. He further showed generate rotation inside metal–organic interfaces, sustained by the Marangoni how chemotaxis can allow selective, time

Nature Chemistry | VOL 12 | September 2020 | 793–794 | www.nature.com/naturechemistry 793 meeting report dependent, and sequential assembly of in compartmentalized microscale objects, program, and suggested strategies, such as catalyst particles. based on DNA-based signal processing and changing the stories that we tell ourselves, The out-of-equilibrium nature of enzyme-mediated interactivity and feedback. which could help both generally and during active matter can often be controlled by This compartmentalization enables, as the current crisis. well-regulated dissipative mechanisms. Mann argued, a modular design in the Ultimately, this virtual symposium Dibyendu Das (IISER Kolkata) highlighted engineering of systems with a reductionist brought together more than 550 participants the importance of intrinsic negative approach. Pall Thordarson (UNSW Sydney) from 46 countries, five continents, feedback to regulate such out-of-equilibrium spoke further on compartmentalization, and a huge spread of time zones. The behaviour in autonomous materials. where the use of polymer amphiphiles to Twitter poster session enjoyed >63,000 Synthetic microtubule analogues were create membrane-mimicking polymersomes engagements, with an average of >600 shown to stop their own formation via allows for the creation of non-spherical per poster, and an interactive Slack accelerated catalytic degradation of the structures that have utility in applications forum facilitated the critical networking building blocks. such as drug delivery. discussions, which are the heart of many In addition to motion, self-reproduction Self-assembled systems based on conference experiences. is another aspect of synthetic biology natural building blocks can also be used as While the COVID-19 pandemic may that requires encoding and translation of structural and functional components for have forced many of us to physically information. Using microfluidics and an (bio) and nanotechnology. distance, the success of this virtual event experimental model of synthetic ribozymes Helena Azevedo (Queen Mary University can serve as a model for overcoming many that autocatalyse their own formation from of London) shared her work on molecularly of the practical and financial barriers for RNA oligomers, Phillipe Nghe (ESPCI engineered peptide nanomaterials as model conference travel in the future. At the same Paris) created a combinatorial process to substrates to unravel the mechanism of time, it exemplifies how systems chemistry investigate reproduction and diversity in enzyme catalysis and how biocatalysis can can unite a variety of areas ranging from these autocatalytic networks. He identified be applied to reveal the molecular dynamics chemical networks to assembling and active design rules for developing chemical systems in self-assembled systems. Jen Heemstra matter, to explore emergent, synergistic with evolutionary characteristics, having (Emory University) talked about ‘bilingual’ phenomena that will address new problems implications for origin-of-life research. biopolymers that bridge peptides and in the years to come. ❐ Working to create a simplified system nucleic acids to access materials that can based on biology, Hannes Mutschler (MPI encode information, create compartments, Helena S. Azevedo1 ✉ , Sarah L. Perry2 ✉ , Biochemistry) discussed the generation of and facilitate intracellular delivery. Peter A. Korevaar3 ✉ and Dibyendu Das4 ✉ a cell-free, partially self-replicating in vitro Inevitably, the virtual event had a 1School of Engineering & Materials Science, translation system that can mimic the session on COVID-19 where Sam Gellman Queen Mary University of London, London, UK. essential features of living matter. (University of Wisconsin–Madison) and 2Department of Chemical Engineering, University Many living or bioinspired systems use Pall Thordarson shared their efforts in of Massachusetts Amherst, Amherst, MA, USA. self-assembly to create compartments that combating the spread of coronavirus 3Institute for Molecules and Materials, Radboud store and exchange chemicals, and facilitate infection. Gellman discussed the University, Nijmegen, the . 4Department chemical reactions. While amphiphiles development of backbone modified peptides of Chemical Sciences, IISER Kolkata, West Bengal, such as surfactants and lipids provide the that can act as inhibitors against COVID- India. most direct parallels to cells, Sarah Perry 19. These helical α/β peptides resisted ✉e-mail: [email protected]; perrys@engin. (University of Massachusetts Amherst) degradation by viral proteases and were umass.edu; [email protected]; explained how association between thought to interact with the spike protein [email protected] oppositely-charged macro-ions, such as of the virus. In a powerful demonstration polymers, proteins, and micelles, provides of the effectiveness of scientific outreach, Published online: 17 August 2020 liquid–liquid phase separation (that is, Thordarson described how his Twitter https://doi.org/10.1038/s41557-020-0537-x complex coacervation) as an alternative thread explaining the importance of soap References strategy to create compartments. Complex in neutralising the coronavirus went ‘viral’ 1. Mattia, E. & Otto, S. Nature Nanotechnol. 10, 111–119 (2015). coacervation has a long history in protocell – a brilliant lesson on the chemistry and 2. Ashkenasy, G., Hermans, T. M., Otto, S. & Taylor, A. F. Chem. Soc. models, and has more recently been nanoscience of soap and viruses. Rev. 46, 2543–2554 (2017). observed in ‘membraneless organelles’ that An unspoken challenge in science 3. Kroiss, D., Ashkenasy, G., Braunschweig, A. B., Tuttle, T. & Ulijn, R. V. Chem. 5, 1917–1920 (2019). enable compartmentalization without the that has been exacerbated by the physical 4. Scalise, D. & Schulman, R. Annu. Rev. Biomed. Eng. 21, presence of an impermeable membrane distancing requirements of the COVID-19 469–493 (2019). barrier. Stephen Mann (University of pandemic is mental health. Jen Heemstra 5. Bai, Y., Chotera, A., Taran, O., Liang, C., Ashkenasy, G. & Lynn, D. G. Chem. Soc. Rev. 47, 5444–5456 (2018). Bristol) demonstrated the potential of addressed the challenges, such as imposter 6. van Esch, J. H., Klajn, R. & Otto, S. Chem. Soc. Rev. 46, protocells towards distributed computation syndrome and the stress of joining a new 5474–5475 (2017).

794 Nature Chemistry | VOL 12 | September 2020 | 793–794 | www.nature.com/naturechemistry