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There has been increasing interest in methods to generate synthetic lipid membranes as key constituents of artificial cells or to develop new tools for remodeling membranes in living cells. However, the biosynthesis of phospholipids involves elaborate enzymatic pathways that are challenging to reconstitute in vitro. An alternative approach is to use chemical reactions to non‐enzymatically generate natural or non‐canonical phospholipids de novo. Previous reports have shown that synthetic lipid membranes can be formed in situ using various ligation chemistries, but these methods lack biocompatibility and/or suffer from slow kinetics at physiological pH. Thus, it would be valuable to develop chemoselective strategies for synthesizing phospholipids from water‐soluble precursors that are compatible with synthetic or living cells Here, we demonstrate that amide‐forming ligations between lipid precursors bearing hydroxylamines and α‐ketoacids (KAs) or potassium acyltrifluoroborates (KATs) can be used to prepare non‐canonical phospholipids at physiological pH conditions. The generated amide‐linked phospholipids spontaneously self‐assemble into cell‐like micron‐sized vesicles similar to natural phospholipid membranes. We show that lipid synthesis using KAT ligation proceeds extremely rapidly, and the high selectivity and biocompatibility of the approach facilitates the in situ synthesis of phospholipids and associated membranes in living cells. [ABSTRACT FROM AUTHOR]

Mimicking the structures and functions of cells to create artificial organelles has spurred the development of efficient strategies for production of hollow nanoreactors with biomimetic catalytic functions. However, such structure are challenging to fabricate and are thus rarely reported. We report the design of hollow nanoreactors with hollow multishelled structure (HoMS) and spatially loaded metal nanoparticles. Starting from a molecular‐level design strategy, well‐defined hollow multishelled structure phenolic resins (HoMS‐PR) and carbon (HoMS‐C) submicron particles were accurately constructed. HoMS‐C serves as an excellent, versatile platform, owing to its tunable properties with tailored functional sites for achieving precise spatial location of metal nanoparticles, internally encapsulated (Pd@HoMS‐C) or externally supported (Pd/HoMS‐C). Impressively, the combination of the delicate nanoarchitecture and spatially loaded metal nanoparticles endow the pair of nanoreactors with size–shape‐selective molecular recognition properties in catalytic semihydrogenation, including high activity and selectivity of Pd@HoMS‐C for small aliphatic substrates and Pd/HoMS‐C for large aromatic substrates. Theoretical calculations provide insight into the pair of nanoreactors with distinct behaviors due to the differences in energy barrier of substrate adsorption. This work provides guidance on the rational design and accurate construction of hollow nanoreactors with precisely located active sites and a finely modulated microenvironment by mimicking the functions of cells. [ABSTRACT FROM AUTHOR]

Life‐like hierarchical architecture shows great potential for advancing intelligent biosensing, but modular expansion of its sensitivity and functionality remains a challenge. Drawing inspiration from intracellular liquid‐liquid phase separation, we discovered that a DNA‐encoded artificial cell with a liquid core (LAC) can enhance peroxidase‐like activity of Hemin and its DNA G‐quadruplex aptamer complex (DGAH) without substrate‐selectivity, unlike its gelled core (GAC) counterpart. The LAC is easily engineered as an ultrasensitive biosensing system, benefiting from DNA′s high programmability and unique signal amplification capability mediated by liquid‐liquid phase separation. As proof of concept, its versatility was successfully demonstrated by coupling with two molecular recognition elements to monitor tumor‐related microRNA and profile cancer cell phenotypes. This scalable design philosophy offers new insights into the design of next generation of artificial cells‐based biosensors. [ABSTRACT FROM AUTHOR]

Transmission of chemical information between cells and across lipid bilayer membranes is of profound significance in many biological processes. The design of synthetic signalling systems is a critical step towards preparing artificial cells with collective behaviour. Here, we report the first example of a synthetic inter‐vesicle signalling system, in which diffusible chemical signals trigger transmembrane ion transport in a manner reminiscent of signalling pathways in biology. The system is derived from novel ortho‐nitrobenzyl and BODIPY photo‐caged ZnII transporters, in which cation transport is triggered by photo‐decaging with UV or red light, respectively. This decaging reaction can be used to trigger the release of the cationophores from a small population of sender vesicles. This in turn triggers the transport of ions across the membrane of a larger population of receiver vesicles, but not across the sender vesicle membrane, leading to overall inter‐vesicle signal transduction and amplification. [ABSTRACT FROM AUTHOR]

The ability to reproduce signal transduction and cellular communication in artificial cell systems is significant in synthetic protobiology. Here, we describe an artificial transmembrane signal transduction through low pH‐mediated formation of the i‐motif and dimerization of DNA‐based artificial membrane receptors, which is coupled to the occurrence of fluorescence resonance energy transfer and the activation of G‐quadruplex/hemin‐mediated fluorescence amplification inside giant unilamellar vesicles. Moreover, an intercellular signal communication model is established when the extravesicular H+ input is replaced by coacervate microdroplets, which activate the dimerization of the artificial receptors, and subsequent fluorescence production or polymerization in giant unilamellar vesicles. This study represents a crucial step towards designing artificial signalling systems with environmental response, and provides an opportunity to establish signalling networks in protocell colonies. [ABSTRACT FROM AUTHOR]

Living organisms compartmentalize their catalytic reactions in membranes for increased efficiency and selectivity. To mimic the organelles of eukaryotic cells, we develop a mild approach for in situ encapsulating enzymes in aqueous‐core silica nanocapsules. In order to confine the sol‐gel reaction at the water/oil interface of miniemulsion, we introduce an aminosilane to the silica precursors, which serves as both catalyst and an amphiphilic anchor that electrostatically assembles with negatively charged hydrolyzed alkoxysilanes at the interface. The semi‐permeable shell protects enzymes from proteolytic attack, and allows the transport of reactants and products. The enzyme‐carrying nanocapsules, as synthetic nano‐organelles, are able to perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in eukaryotic cells. This in situ encapsulation approach provides a versatile platform for the delivery of biomacromolecules. [ABSTRACT FROM AUTHOR]

DNA biotechnology offers intriguing opportunities for amplification‐based sensitive detection. However, spatiotemporally‐controlled manipulation of signal amplification for in situ imaging of the tumor microenvironment remains an outstanding challenge. Here, we demonstrate a DNA‐based strategy that can spatial‐selectively amplify the acidic signal in the extracellular milieu of the tumor to achieve specific imaging with improved sensitivity. The strategy, termed mild acidosis‐targeted amplification (MAT‐amp), leverages the specific acidic microenvironment to engineer tumor cells with artificial DNA receptors through a pH (low) insertion peptide, which permits controlled recruitment of fluorescent amplifiers via a hybridization chain reaction. The acidosis‐responsive amplification cascade enables significant fluorescence enhancement in tumors with a reduced background signal in normal tissues, leading to improved signal‐to‐background ratio. These results highlight the utility of MAT‐amp for in situ imaging of the microenvironment characterized by pH disequilibrium. [ABSTRACT FROM AUTHOR]

Vakayil K. Praveen, a Principal Scientist and Associate Professor in India, has published an article titled "Spontaneous Curvature Induction in an Artificial Bilayer Membrane" in Angewandte Chemie. His research focuses on supramolecular chemistry, self-assembly in aqueous media, stimuli-responsive materials, organic dyes, and photophysics. Praveen is interested in the development of a "truly living artificial cell" and believes that chemistry allows us to study the evolution of particles into complex living matter. He also discusses his career, research adventures, and motivations in the field of chemistry. [Extracted from the article]

The regulation of protein uptake and secretion is crucial for (inter)cellular signaling. Mimicking these molecular events is essential when engineering synthetic cellular systems. A first step towards achieving this goal is obtaining control over the uptake and release of proteins from synthetic cells in response to an external trigger. Herein, we have developed an artificial cell that sequesters and releases proteinaceous cargo upon addition of a coded chemical signal: single‐stranded DNA oligos (ssDNA) were employed to independently control the localization of a set of three different ssDNA‐modified proteins. The molecular coded signal allows for multiple iterations of triggered uptake and release, regulation of the amount and rate of protein release and the sequential release of the three different proteins. This signaling concept was furthermore used to directionally transfer a protein between two artificial cell populations, providing novel directions for engineering lifelike communication pathways inside higher order (proto)cellular structures. [ABSTRACT FROM AUTHOR]

Bottom‐up synthetic biology is the science of building systems that mimic the structure and function of living cells from scratch. To do this, researchers combine tools from chemistry, materials science, and biochemistry to develop functional and structural building blocks to construct synthetic cell‐like systems. The many strategies and materials that have been developed in recent decades have enabled scientists to engineer synthetic cells and organelles that mimic the essential functions and behaviors of natural cells. Examples include synthetic cells that can synthesize their own ATP using light, maintain metabolic reactions through enzymatic networks, perform gene replication, and even grow and divide. In this Review, we discuss recent developments in the design and construction of synthetic cells and organelles using the bottom‐up approach. Our goal is to present representative synthetic cells of increasing complexity as well as strategies for solving distinct challenges in bottom‐up synthetic biology. [ABSTRACT FROM AUTHOR]

Spatiotemporal organization of distinct biological processes in cytomimetic compartments is a crucial step towards engineering functional artificial cells. Mimicking controlled bi‐directional molecular communication inside artificial cells remains a considerable challenge. Here we present photoswitchable molecular transport between programmable membraneless organelle‐like DNA coacervates in a synthetic microcompartment. We use droplet microfluidics to fabricate membraneless non‐fusing DNA coacervates by liquid‐liquid phase separation in a water‐in‐oil droplet, and employ the interior DNA coacervates as artificial organelles to imitate intracellular communication via photo‐regulated uni‐ and bi‐directional transfer of biomolecules. Our results highlight a promising new route to assembly of multicompartment artificial cells with functional networks. [ABSTRACT FROM AUTHOR]

Catalyzing biochemical reactions with enzymes and communicating with neighboring cells via chemical signaling are two fundamental cellular features that play a critical role in maintaining the homeostasis of organisms. Herein, we present an artificial enzyme (AE) facilitated signal transfer between artificial cells (ACs) and mammalian HepG2 cells. We synthesize metalloporphyrins (MPs) based AEs that mimic cytochrome P450 enzymes (CYPs) to catalyze a dealkylation and a hydroxylation reaction, exemplified by the conversion of resorufin ethyl ether (REE) to resorufin and coumarin (COU) to 7‐hydroxycoumarin (7‐HC), respectively. The AEs are immobilized in hydrogels to produce ACs that generate the two diffusive fluorophores, which can diffuse into HepG2 cells and result in dual intracellular emissions. This work highlights the use of AEs to promote AC to mammalian signal transfer, which opens up new opportunities for integrating the synthetic and living world with a bottom‐up strategy. [ABSTRACT FROM AUTHOR]

The MinDE proteins from E. coli have received great attention as a paradigmatic biological pattern‐forming system. Recently, it has surfaced that these proteins do not only generate oscillating concentration gradients driven by ATP hydrolysis, but that they can reversibly deform giant vesicles. In order to explore the potential of Min proteins to actually perform mechanical work, we introduce a new model membrane system, flat vesicle stacks on top of a supported lipid bilayer. MinDE oscillations can repeatedly deform these flat vesicles into tubules and promote progressive membrane spreading through membrane adhesion. Dependent on membrane and buffer compositions, Min oscillations further induce robust bud formation. Altogether, we demonstrate that under specific conditions, MinDE self‐organization can result in work performed on biomimetic systems and achieve a straightforward mechanochemical coupling between the MinDE biochemical reaction cycle and membrane transformation. [ABSTRACT FROM AUTHOR]

The construction of artificial cells from inanimate molecular building blocks is one of the grand challenges of our time. In addition to being used as simplified cell models to decipher the rules of life, artificial cells have the potential to be designed as micromachines deployed in a host of clinical and industrial applications. The attractions of engineering artificial cells from scratch, as opposed to re‐engineering living biological cells, are varied. However, it is clear that artificial cells cannot currently match the power and behavioural sophistication of their biological counterparts. Given this, many in the synthetic biology community have started to ask: is it possible to interface biological and artificial cells together to create hybrid living/synthetic systems that leverage the advantages of both? This article will discuss the motivation behind this cellular bionics approach, in which the boundaries between living and non‐living matter are blurred by bridging top‐down and bottom‐up synthetic biology. It details the state of play of this nascent field and introduces three generalised hybridisation modes that have emerged. [ABSTRACT FROM AUTHOR]

The non‐enzymatic replication of the primordial genetic material is thought to have enabled the evolution of early forms of RNA‐based life. However, the replication of oligonucleotides long enough to encode catalytic functions is problematic due to the low efficiency of template copying with mononucleotides. We show that template‐directed ligation can assemble long RNAs from shorter oligonucleotides, which would be easier to replicate. The rate of ligation can be greatly enhanced by employing a 3′‐amino group at the 3′‐end of each oligonucleotide, in combination with an N‐alkyl imidazole organocatalyst. These modifications enable the copying of RNA templates by the multistep ligation of tetranucleotide building blocks, as well as the assembly of long oligonucleotides using short splint oligonucleotides. We also demonstrate the formation of long oligonucleotides inside model prebiotic vesicles, which suggests a potential route to the assembly of artificial cells capable of evolution. [ABSTRACT FROM AUTHOR]

This Essay focuses briefly on early studies elaborated by natural and chemical philosophers, and the once‐called synthetic biologists, who postulated the transition from inanimate to animate matter and even foresaw the possibility of creating artificial life on the basis of physical and chemical principles only. Such ideas and speculations, ranging from soundness to weirdness, paved however the way to current developments in areas like abiotic pattern formation, cell compartmentalization, biomineralization, or the origin of life itself. In particular, the generation of biomorphs and their relationship to microfossils represents an active research domain and seems to be the logical way to bring the historical work up to the future, as some scientists are trying to make artificial cells. The last sections of this essay will also highlight modern science aimed at understanding what life is and, whether or not, it can be redefined in chemical terms. [ABSTRACT FROM AUTHOR]

Targeted vesicle fusion is a promising approach to selectively control interactions between vesicle compartments and would enable the initiation of biological reactions in complex aqueous environments. Here, we explore how two features of vesicle membranes, DNA tethers and phase‐segregated membranes, promote fusion between specific vesicle populations. Membrane phase‐segregation provides an energetic driver for membrane fusion that increases the efficiency of DNA‐mediated fusion events. The orthogonality provided by DNA tethers allows us to direct fusion and delivery of DNA cargo to specific vesicle populations. Vesicle fusion between DNA‐tethered vesicles can be used to initiate in vitro protein expression to produce model soluble and membrane proteins. Engineering orthogonal fusion events between DNA‐tethered vesicles provides a new strategy to control the spatiotemporal dynamics of cell‐free reactions, expanding opportunities to engineer artificial cellular systems. [ABSTRACT FROM AUTHOR]

Bio‐inspired functional microcapsules have attracted increasing attention in many fields from physical/chemical science to artificial‐cell engineering. Although particle‐stabilised microcapsules are advantageous for their stability and functionalisation potential, versatile methods for their functionalisation are desired to expand their possibilities. This study reports a water‐in‐oil microdroplet stabilised with amphiphilic DNA origami nanoplates. By utilising DNA nanotechnology, DNA nanoplates were designed as a nanopore device for ion transportation and to stabilise the oil–water interface. Microscopic examination revealed the microcapsule formed by the accumulation of amphiphilic DNA nanoplates at the oil–water interface. Ion current measurements revealed the nanoplate pores functioned as channel to transport ions. These findings provide a general strategy for the programmable design of microcapsules to engineer artificial cells and molecular robots. [ABSTRACT FROM AUTHOR]

Cells can form membraneless organelles by liquid–liquid phase separation. As these organelles are highly dynamic, it is crucial to understand the kinetics of these phase transitions. Here, we use droplet‐based microfluidics to mix reagents by chaotic advection and observe nucleation, growth, and coarsening in volumes comparable to cells (pL) and on timescales of seconds. We apply this platform to analyze the dynamics of synthetic organelles formed by the DEAD‐box ATPase Dhh1 and RNA, which are associated with the formation of processing bodies in yeast. We show that the timescale of phase separation decreases linearly as the volume of the compartment increases. Moreover, the synthetic organelles coarsen into one single droplet via gravity‐induced coalescence, which can be arrested by introducing a hydrogel matrix that mimics the cytoskeleton. This approach is an attractive platform to investigate the dynamics of compartmentalization in artificial cells. [ABSTRACT FROM AUTHOR]

Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time‐dependent dynamics to discriminate the endogenous and exogenous inputs. For a real‐time stimulation of cell signaling, we synthesized a photo‐cleavable metal–nitrosyl complex, [CoIII(MDAP)(NO)(CH3CN)]2+ (MDAP=N,N′‐dimethyl‐2,11‐diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosol, and used this to study the extracellular signal‐regulated kinases (ERKs), revealing how cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be to understand how diverse cellular signaling networks are dynamically interconnected and also to control drug delivery systems. [ABSTRACT FROM AUTHOR]

An artificial photosynthetic (APS) system consisting of a photoanodic semiconductor that harvests solar photons to split H2O, a Ni‐SNG cathodic catalyst for the dark reaction of CO2 reduction in a CO2‐saturated NaHCO3 solution, and a proton‐conducting membrane enabled syngas production from CO2 and H2O with solar‐to‐syngas energy‐conversion efficiency of up to 13.6 %. The syngas CO/H2 ratio was tunable between 1:2 and 5:1. Integration of the APS system with photovoltaic cells led to an impressive overall quantum efficiency of 6.29 % for syngas production. The largest turnover frequency of 529.5 h−1 was recorded with a photoanodic N‐TiO2 nanorod array for highly stable CO production. The CO‐evolution rate reached a maximum of 154.9 mmol g−1 h−1 in the dark compartment of the APS cell. Scanning electrochemical–atomic force microscopy showed the localization of electrons on the single‐nickel‐atom sites of the Ni‐SNG catalyst, thus confirming that the multielectron reduction of CO2 to CO was kinetically favored. [ABSTRACT FROM AUTHOR]

Gel‐based artificial organelles have been developed that enable sequence‐specific and programmable localization of cell‐free transcription and translation reactions inside an artificial cellular system. To this end, we utilize agarose microgels covalently modified with DNA templates coding for various functions and encapsulate them into emulsion droplets. We show that RNA signals transcribed from transcription organelles can be specifically targeted to capture organelles via hybridization to the corresponding DNA addresses. We also demonstrate that mRNA molecules, produced from transcription organelles and controlled by toehold switch riboregulators, are only translated in translation organelles containing their cognate DNA triggers. Spatial confinement of transcription and translation in separate organelles is thus superficially similar to gene expression in eukaryotic cells. Combining communicating gel spheres with specialized functions opens up new possibilities for programming artificial cellular systems at the organelle level. Chemical processes within biological cells often occur inside organelles. This high degree of intracellular organization has inspired the development of gel‐based artificial organelles that enable sequence‐specific and programmable localization of cell‐free transcription and translation reactions inside an artificial cellular system. [ABSTRACT FROM AUTHOR]

In living systems, there are many autonomous and oscillatory phenomena to sustain life, such as heart contractions and breathing. At the microscopic level, oscillatory shape deformations of cells are often observed in dynamic behaviors during cell migration and morphogenesis. In many cases, oscillatory behaviors of cells are not simplistic but complex with diverse deformations. So far, we have succeeded in developing self-oscillating polymers and gels, but complex oscillatory behaviors mimicking those of living cells have yet to be reproduced. Herein, we report a cell-like hollow sphere composed of self-oscillating microgels, that is, a colloidosome, that exhibits drastic shape oscillation in addition to swelling/deswelling oscillations driven by an oscillatory reaction. The resulting oscillatory profile waveform becomes markedly more complex than a conventional one. Especially for larger colloidosomes, multiple buckling and moving buckling points are observed to be analogous to cells. [ABSTRACT FROM AUTHOR]

Water-containing organic solutions are widespread reaction media in organic synthesis and catalysis. This type of multicomponent liquid system has a number of unique properties because of the tendency for water to self-organize in mixtures with other liquids. The characterization of these water domains is a challenging task because of their soft and dynamic nature. In the present study, the morphology and dynamics of micrometer- and nanometer-scale water-containing compartments in ionic liquids were directly observed by electron microscopy. A variety of morphologies, including isolated droplets, dense structures, aggregates, and 2D meshworks, have been experimentally detected and studied. Using the developed method, the impact of water on the acid-catalyzed biomass conversion reaction was studied at the microscopic level. The process that produced nanostructured domains in solution led to better yields and higher selectivities compared with reactions involving the bulk system. [ABSTRACT FROM AUTHOR]

B The most important factor in the choice of my current research topic was b my vision for the construction of artificial light-harvesting organelles. I The most important factor in the choice of my current research topic was my vision for the construction of artificial light-harvesting organelles ... My biggest motivation is uncovering the unknown i ..." Find out more about Alexander Ayzner in his Introducing ... Profile. Behind the Science Our research vision is to form artificial mimics to light-harvesting organelles. [Extracted from the article]

Difficulties in constructing complex lipid/protein membranes have severely limited the development of functional artificial cells endowed with vital membrane-related functions. The Sec translocon membrane channel, which mediates the insertion of membrane proteins into the plasma membrane, was constructed in the membrane of lipid vesicles through in vitro expression of its component proteins. The components of the Sec translocon were synthesized from their respective genes in the presence of liposomes, thereby bringing about a functional complex. The synthesized E. coli Sec translocon mediated the membrane translocation of single- and multi-span membrane proteins. The successful translocation of a functional peptidase into the liposome lumen further confirmed the proper insertion of the translocon complex. Our results demonstrate the feasible construction of artificial cells, the membranes of which can be functionalized by directly decoding genetic information into membrane functions. [ABSTRACT FROM AUTHOR]

Structurally colored materials could potentially replace dyes and pigments in many applications, but it is challenging to fabricate structural colors that mimic the appearance of absorbing pigments. We demonstrate the microfluidic fabrication of 'photonic pigments' consisting of microcapsules containing dense amorphous packings of core-shell colloidal particles. These microcapsules show non-iridescent structural colors that are independent of viewing angle, a critical requirement for applications such as displays or coatings. We show that the design of the microcapsules facilitates the suppression of incoherent and multiple scattering, enabling the fabrication of photonic pigments with colors spanning the visible spectrum. Our findings should provide new insights into the design and synthesis of materials with structural colors. [ABSTRACT FROM AUTHOR]

Enzyme-filled polystyrene- b-poly(3-(isocyano- L-alanyl-aminoethyl)thiophene) (PS- b-PIAT) nanoreactors are encapsulated together with free enzymes and substrates in a larger polybutadiene- b-poly(ethylene oxide) (PB- b-PEO) polymersome, forming a multicompartmentalized structure, which shows structural resemblance to the cell and its organelles. An original cofactor-dependent three-enzyme cascade reaction is performed, using either compatible or incompatible enzymes, which takes place across multiple compartments. [ABSTRACT FROM AUTHOR]

The article offers information on several chemistry research featured in the journal's sister publications which include oxygen reduction, artificial cells, and antiviral agents.

The article discusses a study on an electrophoretic polymer assembly (EPA) technique for preparing nanocapsules and microcapsules. The EPA technique involves using electrophoresis to produce particles coated with multiple polymer layers and polymer multilayer capsules. The technique also uses agarose as a natural microfluidic hydrogel to immobilize the particles. The implication of the technique for layer-by-layer assembly of polymers is explained.

The article discusses the profile of Masayuki Endo, an Associate Professor at the Institute for Integrated Cell-Material Sciences in Kyoto University, Japan focusing on his works on topics related to molecular robotics, artificial cells, and nucleic acid nanotechnology. The author also notes that "Tchaikovskys ballet music" is his favorite. Endo's top paper the were published regarding DNA Origami, need for a programmed-assembly system. Websites that provide assess to his works are noted.