Self‐Assembled Supramolecular Channels: Toward Biomimetic Materials for Directional Translocation

Feedback-controlled chemical reaction networks (FCRNs) are indispensable for various biological processes, such as cellular mechanisms, patterns, and signaling pathways. Through the intricate interplay of many feedback loops (FLs), FCRNs maintain a stable internal cellular environment. Currently, creating minimalistic synthetic cells is the long-term objective of systems chemistry, which is motivated by such natural integrity. The design, kinetic optimization, and analysis of FCRNs to exhibit functions akin to those of a cell still pose significant challenges. Indeed, reaching synthetic homeostasis is essential for engineering synthetic cell components. However, maintaining homeostasis in artificial systems against various agitations is a difficult task. Several biological events can provide us with guidelines for a conceptual understanding of homeostasis, which can be further applicable in designing artificial synthetic systems. In this regard, we organize our review with artificial homeostasis systems driven by FCRNs at different length scales, including homogeneous, compartmentalized, and soft material systems. First, we stretch a quick overview of FCRNs in different molecular and supramolecular systems, which are the essential toolbox for engineering different nonlinear functions and homeostatic systems. Moreover, the existing history of synthetic homeostasis in chemical and material systems and their advanced functions with self-correcting, and regulating properties are also emphasized.

Feedback‐controlled chemical reaction networks (FCRNs) are indispensable for various biological processes, such as cellular mechanisms, patterns, and signaling pathways. Through the intricate interplay of many feedback loops (FLs), FCRNs maintain a stable internal cellular environment. Currently, creating minimalistic synthetic cells is the long‐term objective of systems chemistry, which is motivated by such natural integrity. The design, kinetic optimization, and analysis of FCRNs to exhibit functions akin to those of a cell still pose significant challenges. Indeed, reaching synthetic homeostasis is essential for engineering synthetic cell components. However, maintaining homeostasis in artificial systems against various agitations is a difficult task. Several biological events can provide us with guidelines for a conceptual understanding of homeostasis, which can be further applicable in designing artificial synthetic systems. In this regard, we organize our review with artificial homeostasis systems driven by FCRNs at different length scales, including homogeneous, compartmentalized, and soft material systems. First, we stretch a quick overview of FCRNs in different molecular and supramolecular systems, which are the essential toolbox for engineering different nonlinear functions and homeostatic systems. Moreover, the existing history of synthetic homeostasis in chemical and material systems and their advanced functions with self‐correcting, and regulating properties are also emphasized.

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Within biological systems, natural channels and pores transport metabolites across the cell membranes. Researchers have explored artificial ion-channel architectures as potential mimics of natural ionic conduction. All these synthetic systems have produced an impressive collection of alternative artificial ion-channels. Amazingly, researchers have made far less progress in the area of synthetic water channels. The development of synthetic biomimetic water channels and pores could contribute to a better understanding of the natural function of protein channels and could offer new strategies to generate highly selective, advanced water purification systems. Despite the imaginative work by synthetic chemists to produce sophisticated architectures that confine water clusters, most synthetic water channels have used natural proteins channels as the selectivity components, embedded in the diverse arrays of bioassisted artificial systems. These systems combine natural proteins that present high water conductance states under natural conditions with artificial lipidic or polymeric matrixes. Experimental results have demonstrated that natural biomolecules can be used as bioassisted building blocks for the construction of highly selective water transport through artificial membranes. A next step to further the potential of these systems was the design and construction of simpler compounds that maintain the high conduction activity obtained with natural compounds leading to fully synthetic artificial biomimetic systems. Such studies aim to use constitutional selective artificial superstructures for water/proton transport to select functions similar to the natural structures. Moving to simpler water channel systems offers a chance to better understand mechanistic and structural behaviors and to uncover novel interactive water-channels that might parallel those in biomolecular systems. This Account discusses the incipient development of the first artificial water channels systems. We include only systems that integrate synthetic elements in their water selective translocation unit. Therefore, we exclude peptide channels because their sequences derive from the proteins in natural channels. We review many of the natural systems involved in water and related proton transport processes. We describe how these systems can fit within our primary goal of maintaining natural function within bioassisted artificial systems. In the last part of the Account, we present several inspiring breakthroughs from the last decade in the field of biomimetic artificial water channels. Researchers have synthesized and tested hydrophobic, hydrophilic and hybrid nanotubular systems. All these examples demonstrate how the novel interactive water-channels can parallel biomolecular systems. At the same time these simpler artificial water channels offer a means of understanding the molecular-scale hydrodynamics of water for many biological scenarios.

The natural KcsA K+ channel, one of the best-characterized biological pore structures, conducts K+ cations at high rates while excluding Na+ cations. The KcsA K+ channel is of primordial inspiration for the design of artificial channels. Important progress in improving conduction activity and K+ /Na+ selectivity has been achieved with artificial ion-channel systems. However, simple artificial systems exhibiting K+ /Na+ selectivity and mimicking the biofunctions of the KcsA K+ channel are unknown. Herein, an artificial ion channel formed by H-bonded stacks of squalyl crown ethers, in which K+ conduction is highly preferred to Na+ conduction, is reported. The K+ -channel behavior is interpreted as arising from discreet stacks of dimers resulting in the formation of oligomeric channels, in which transport of cations occurs through macrocycles mixed with dimeric carriers undergoing dynamic exchange within the bilayer membrane. The present highly K+ -selective macrocyclic channel can be regarded as a biomimetic alternative to the KcsA channel.

The bioinspired design and synthesis of building blocks and their assemblies by the supramolecular approach has ever fascinated scientists to utilize such artificial systems for numerous purposes. Flexibility is a basic feature of natural systems. However, in artificial systems this is difficult to control, especially if there is no preorganization of the component(s) of a system. We have designed and synthesized a series of C3 -symmetric N-bridged flexible receptors and successfully utilized them to selectively entrap the notorious and toxic nitrate anion in aqueous medium. This was the first report of highest binding affinity for the nitrate anion in aqueous medium. An impressive self-sorting phenomenon of reversibly formed hydrogen-bonded capsules, which self-assembled from flexible tripodal receptors having branches of similar size and bearing the same amide functionality, has been disclosed. Encapsulated nitrate anion has been further utilized for the photochemical [2+2] cycloaddition reaction for the synthesis of strained four-membered ring structures through dynamic self-assembly. In this Personal Account, we summarize these results showing the utility of naturally inspired flexibility in artificial systems.

Transmembrane signal transduction is of profound significance in many biological processes. The dimerization of cell-surface receptors is one prominent mechanism by which signals are transmitted across the membrane and trigger intracellular cascade amplification reactions. Recreating such processes in artificial systems has potential applications in sensing, drug delivery, bioengineering, and providing a new route for a deep understanding of fundamental biological processes. However, it remains a challenge to design artificial signal transduction systems working by the receptor dimerization mechanism in a predictable and smart manner. Here, benefitting from DNA with features of programmability, controllability, and flexible design, we use DNA as a building material to construct an artificial system mimicking dimerization of receptors for signal transduction and cascade amplification. DNA-based membrane-spanning receptor analogues are designed to recognize external signals, which drives two receptors into close spatial proximity to activate DNAzymes inside the cell-mimicking system. The activation of the DNAzyme initiates the catalyzed cleavage of encapsulated substrates and leads to the release of fluorescent second messengers for signal amplification. Such an artificial signal transduction system extends the range of biomimetic DNA-based signaling systems, providing a new avenue to study natural cell signaling processes and artificially regulate biological processes.

Different types of natural K+ channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+ channels by rebuilding the core modules of natural K+ channels in artificial systems. All the channels displayed high selectivity for K+ over Na+ and exhibited a selectivity sequence of K+ ≈Rb+ during the transport process, which is highly consistent with the cation permeability characteristics of natural K+ channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+ , disrupting the cellular K+ homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+ channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+ channels can be mimicked in synthetic channels.

Different types of natural K+channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+channels by rebuilding the core modules of natural K+channels in artificial systems. All the channels displayed high selectivity for K+over Na+and exhibited a selectivity sequence of K+≈Rb+during the transport process, which is highly consistent with the cation permeability characteristics of natural K+channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+, disrupting the cellular K+homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+channels can be mimicked in synthetic channels.

The immense flow of sun power that hits the atmosphere, approximately 170000 trillion watts (170 PW), drives large scale natural processes such as photosynthesis, which are key to sustaining life in the biosphere. The conversion of solar light energy in the photosynthetic process is done by complex supramolecular architectures which convert the photon flux into chemical fuel. This operation is enabled by electronic excited states residing in the molecular subunits of photosynthetic systems. These systems accept, store and transfer the excitation energy in a concerted temporal and spatial sequence. In the last 20 years we have witnessed the development of supramolecular photochemistry. The assembly by design of synthetic molecular fragments having specific basic functions (e.g. light harvesting) to build up a supramolecular architecture capable of capturing photons and delivering a superior action (e.g. energy conversion, mechanical motion) is the basic concept of the discipline. This research can ultimately be viewed as a kind of electronic excited state engineering, in which chemists make and test supramolecular systems which deliver a specific action, but only when they are properly designed in terms of the excited state interactions among their components—as found in nature. Thus, a huge number of supramolecular photoactive systems, for example light-powered nanomachines or prototype artificial photosynthetic modules, have been prepared over the years. When engineering artificial photoactive supramolecular systems researchers are often puzzled by problems related to the improvement and/or tuning of the electronic properties of the molecules they wish to assemble. This challenging work may have to do, for instance, with the increase of absorption in a given spectral window, the tuning of the luminescence colour, or the prolongation of an excited-state lifetime. The last issue is particularly important because the duration of an electronic excited state largely dictates its final destiny, especially in supramolecular systems. In a seminal paper from 1992, Ford and Rodgers first reported that the luminescent metal-to-ligand-charge transfer triplet excited state (MLCT*) of a Rupolypyridine complex exhibits a prolonged lifetime (11-fold) when covalently linked to a pyrene fragment via a hydrocarbon chain. The reason for this unusual and potentially interesting behaviour is that the p-p triplet excited state of the pyrene unit (pp*) is lower-lying and almost isoenergetic to the MLCT* level of the Ru-complex moiety and, in solution at room temperature, they may undergo thermal equilibration upon MLCT*!pp* energy transfer followed by back-transfer of energy, as depicted in Figure 1. The lifetime prolongation relies on the temporary storage of the excitation energy on the long-lived pyrene triplet level, which practically acts as an energy reservoir, a role reminiscent of a hydroelectric basin. Eventually, this gives back the excess energy to the metal complex which undergoes delayed deactivation. The engineering concept of this photoactive dyad encompasses two crucial features: a) the reservoir lifetime (pyrene triplet) must be significantly longer than that of the Ru-based MLCT* level ; b) the thermal rate of energy back-transfer (kb in Figure 1) must be significantly faster

Collective behaviour in nature provides a source of inspiration to engineer artificial collective adaptive systems, due to their mechanisms favouring adaptation to environmental changes and enabling complex emergent behaviour to arise from a relatively simple behaviour of individual entities. As part of our ongoing research, we study the social amoeba Dictyostelium discoideum to derive agent-based models and mechanisms that we can then exploit in artificial systems, in particular in swarm robotics. In this paper, we present a selection of agent-based models of the aggregation phase of D. discoideum, their corresponding biological illustrations and how we used them as an inspiration for transposing this behaviour into swarms of Kilobots. We focus on the stream-breaking phenomenon occurring during the aggregation phase of the life cycle of D. discoideum. Results show that the breakup of aggregation streams depends on cell density, motility, motive force and the concentration of cAMP and CF. The breakup also comes with the appearance of late centres. Our computational results show similar behaviour to our biological experiments, using Ax2(ka) strain. For swarm robotics experiments, we focus on signalling and aggregation towards a centre.

Artificial life is a research field studying what processes and properties define life, based on a multidisciplinary approach spanning the physical, natural, and computational sciences. Artificial life aims to foster a comprehensive study of life beyond "life as we know it" and toward "life as it could be," with theoretical, synthetic, and empirical models of the fundamental properties of living systems. While still a relatively young field, artificial life has flourished as an environment for researchers with different backgrounds, welcoming ideas, and contributions from a wide range of subjects. Hybrid Life brings our attention to some of the most recent developments within the artificial life community, rooted in more traditional artificial life studies but looking at new challenges emerging from interactions with other fields. Hybrid Life aims to cover studies that can lead to an understanding, from first principles, of what systems are and how biological and artificial systems can interact and integrate to form new kinds of hybrid (living) systems, individuals, and societies. To do so, it focuses on three complementary perspectives: theories of systems and agents, hybrid augmentation, and hybrid interaction. Theories of systems and agents are used to define systems, how they differ (e.g., biological or artificial, autonomous, or nonautonomous), and how multiple systems relate in order to form new hybrid systems. Hybrid augmentation focuses on implementations of systems so tightly connected that they act as a single, integrated one. Hybrid interaction is centered around interactions within a heterogeneous group of distinct living and nonliving systems. After discussing some of the major sources of inspiration for these themes, we will focus on an overview of the works that appeared in Hybrid Life special sessions, hosted by the annual Artificial Life Conference between 2018 and 2022. This article is categorized under: Neuroscience > Cognition Philosophy > Artificial Intelligence Computer Science and Robotics > Robotics.

Biological mechanosensation has been a source of inspiration for advancements in artificial sensory systems. Animals rely on sensory feedback to guide and adapt their behaviors and are equipped with a wide variety of sensors that carry stimulus information from the environment. Hair and hair-like sensors have evolved to support survival behaviors in different ecological niches. Here, we review the diversity of biological hair and hair-like sensors across the animal kingdom and their roles in behaviors, such as locomotion, exploration, navigation, and feeding, which point to shared functional properties of hair and hair-like structures among invertebrates and vertebrates. By reviewing research on the role of biological hair and hair-like sensors in diverse species, we aim to highlight biological sensors that could inspire the engineering community and contribute to the advancement of mechanosensing in artificial systems, such as robotics.

Artificial light-harvesting systems, an elegant way to capture, transfer and utilize solar energy, have attracted great attention in recent years. As the primary step of natural photosynthesis, the principle of light-harvesting systems has been intensively investigated, which is further employed for artificial construction of such systems. Supramolecular self-assembly is one of the feasible methods for building artificial light-harvesting systems, which also offers an advantageous pathway for improving light-harvesting efficiency. Many artificial light-harvesting systems based on supramolecular self-assembly have been successfully constructed at the nanoscale with extremely high donor/acceptor ratios, energy transfer efficiency and the antenna effect, which manifests that self-assembled supramolecular nanosystems are indeed a viable way for constructing efficient light-harvesting systems. Non-covalent interactions of supramolecular self-assembly provide diverse approaches to improve the efficiency of artificial light-harvesting systems. In this review, we summarize the recent advances in artificial light-harvesting systems based on self-assembled supramolecular nanosystems. The construction, modulation, and applications of self-assembled supramolecular light-harvesting systems are presented, and the corresponding mechanisms, research prospects and challenges are also briefly highlighted and discussed.

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), a naturally occurring anion channel essential for numerous biological processes, possesses a positively charged ion conduction pathway within its transmembrane domain, which serves as the core module for promoting the movement of anions across cell membranes. In this study, we developed novel artificial anion channels by rebuilding the positively charged ion permeation pathway of the CFTR in artificial systems. These synthetic molecules can be efficiently inserted into lipid bilayers to form artificial ion channels, which exhibit a preference for anions during the transmembrane transport process. More importantly, the positively charged amino acid residues located in the ion permeation pathway of these artificial channels can promote the transmembrane transport of anions through electrostatic interactions, which is consistent with the mechanism of anion transmembrane transport achieved by CFTR.