Spatial Organization in Proteinaceous Membrane‐Stabilized Coacervate Protocells

As a model protocell, the membrane‐free coacervate microdroplet is widely utilized in functional studies to provide insights into the physicochemical properties of the cell and to engineer cytomimetic soft technologies; however, the lack of a discrete membrane contributes to its instability and limits further application. Herein, a strategy is developed to fabricate a hybrid protocell based on the self‐assembly of a proteinaceous membrane at the surface of coacervate microdroplets driven by a combination of electrostatic adhesion and steric/hydrophilic surface buoyancy. The semipermeable proteinaceous membrane can enhance coacervate stability obviously without compromising sequestration behavior. Significantly, such hybrid protocells demonstrate spatial organization whereby various functional enzymes can be located in discrete regions, which facilitates an on/off modulation for a cascade enzymatic reaction along with enhanced chemical communication between subpopulations.     

Spontaneous Growth and Division in Self‐Reproducing Inorganic Colloidosomes

Self‐reproduction in compartmentalized chemical ensembles is a central issue for the development of new materials and processes capable of autonomous behavior, self‐amplification and artificial evolution. Current approaches to synthetic cellularity focus primarily on self‐assembled soft matter systems such as membrane‐bounded lipid vesicles, which have sufficient structural plasticity to undergo growth and division. Steps towards inorganic protocells are being advanced, but self‐reproduction in these more structurally robust micro‐compartments has not been demonstrated. Here, a primitive form of growth and division involving inorganic colloidosomes (Pickering emulsions), comprising aqueous micro‐droplets enclosed by an ultrathin membrane of silica nanoparticles, is shown. Growth of the colloidosomes is induced by organosilane‐mediated methanol formation, and results in a localized rupture of the inorganic membrane followed by outgrowth and separation of a second‐generation protocell, which is stabilized by de novo nanoparticle assembly. These observations provide a first step towards synthetic cell‐like inorganic materials capable of chemically induced self‐reproduction.     

Rapid Growth and Fusion of Protocells in Surface‐Adhered Membrane Networks

Elevated temperatures might have promoted the nucleation, growth, and replication of protocells on the early Earth. Recent reports have shown evidence that moderately high temperatures not only permit protocell assembly at the origin of life, but can have actively supported it. Here, the fast nucleation and growth of vesicular compartments from autonomously formed lipid networks on solid surfaces, induced by a moderate increase in temperature, are shown. Branches of the networks, initially consisting of self‐assembled interconnected nanotubes, rapidly swell into microcompartments which can spontaneously encapsulate RNA fragments. The increase in temperature further causes fusion of adjacent network‐connected compartments, resulting in the redistribution of the RNA. The experimental observations and the mathematical model indicate that the presence of nanotubular interconnections between protocells facilitates the fusion process.     

Invasion and Defense Interactions between Enzyme‐Active Liquid Coacervate Protocells and Living Cells

The design and construction of mutual interaction models between artificial microsystems and living cells have the potential to open a wide range of novel applications in biomedical and biomimetic technologies. In this study, an artificial form of invasion‐defense mutual interactions is established in a community of glucose oxidase (GOx)‐containing liquid coacervate microdroplets and living cells, which interact via enzyme‐mediated reactive oxygen species (ROS) damage. The enzyme‐containing coacervate microdroplets, formed via liquid–liquid phase separation, act as invader protocells to electrostatically bind with the host HepG2 cell, resulting in assimilation. Subsequently, the glucose oxidation in the liquid coacervates initiates the generation of H₂O₂, which serves as an ROS resource to block cell proliferation. As a defense strategy, introduction of catalase (CAT) into the host cells is exploited to resist the ROS damage. CAT‐mediated decomposition of H₂O₂ leads to the ROS scavenging and results in the recovery of cell viability. The results obtained in the current study highlight the remarkable opportunities for the development of mutual interacting communities on the interface of artificial protocells/living cells. They also provide a new approach for engineering cellular behaviors through exploiting artificial nonliving microsystems.     

Chemical Information Exchange in Organized Protocells and Natural Cell Assemblies with Controllable Spatial Positions

An ultrasound‐based platform is established to prepare homogenous arrays of giant unilamellar vesicles (GUVs) or red blood cell (RBCs), or hybrid assemblies of GUV/RBCs. Due to different responses to the modulation of the acoustic standing wave pressure field between the GUVs and RBCs, various types of protocell/natural cell hybrid assemblies are prepared with the ability to undergo reversible dynamic reconfigurations from vertical to horizontal alignments, or from 1D to 2D arrangements. A two‐step enzymatic cascade reaction between transmitter glucose oxidase‐containing GUVs and peroxidase‐active receiver RBCs is used to implement chemical signal transduction in the different hybrid micro‐arrays. Taken together, the obtained results suggest that the ultrasound‐based micro‐array technology can be used as an alternative platform to explore chemical communication pathways between protocells and natural cells, providing new opportunities for bottom‐up synthetic biology.     

Spontaneous Structuration in Coacervate‐Based Protocells by Polyoxometalate‐Mediated Membrane Assembly

Molecularly crowded, polyelectrolyte/ribonucleotide‐enriched membrane‐free coacervate droplets are transformed into membrane‐bounded sub‐divided vesicles by using a polyoxometalate‐mediated surface‐templating procedure. The coacervate to vesicle transition results in reconstruction of the coacervate micro‐droplets into novel three‐tiered micro‐compartments comprising a semi‐permeable negatively charged polyoxometalate/polyelectrolyte outer membrane, a sub‐membrane coacervate shell, and an internal aqueous lumen. We demonstrate that organic dyes, ssDNA, magnetic nanoparticles and enzymes can be concentrated into the interior of the micro‐compartments by sequestration into the coacervate micro‐droplets prior to vesicle formation. The vesicle‐encapsulated proteins are inaccessible to proteases in the external medium, and can be exploited for the spatial localization and coupling of two‐enzyme cascade reactions within single or between multiple populations of hybrid vesicles dispersed in aqueous media.     

Enzymatically Powered Surface‐Associated Self‐Motile Protocells

Cell motility is central to processes such as wound healing, immune cell surveillance, and embryonic development. Motility requires the conversion of chemical to mechanical energy. An active area of research is to create motile particles, such as microswimmers, using catalytic and enzymatic reactions. Here, autonomous motion is demonstrated in adhesive polymer‐based protocells by incorporating and harnessing the energy production of an enzymatic reaction. Biotinylated polymer vesicles that encapsulate catalase, an enzyme which converts hydrogen peroxide to water and oxygen, are prepared and these vesicles are adhered weakly to avidin‐coated surfaces. Upon addition of hydrogen peroxide, which diffuses across the membrane, catalase activity generates a differential impulsive force that enables the breakage and reformation of biotin–avidin bonds, leading to diffusive vesicle motion resembling random motility. The random motility requires catalase, increases with the concentration of hydrogen peroxide, and needs biotin–avidin adhesion. Thus, a protocellular mimetic of a motile cell.     

Biomimicry of Cellular Motility and Communication Based on Synthetic Soft‐Architectures

Cells, sophisticated membrane‐bound units that contain the fundamental molecules of life, provide a precious library for inspiration and motivation for both society and academia. Scientists from various disciplines have made great endeavors toward the understanding of the cellular evolution by engineering artificial counterparts (protocells) that mimic or initiate structural or functional cellular aspects. In this regard, several works have discussed possible building blocks, designs, functions, or dynamics that can be applied to achieve this goal. Although great progress has been made, fundamental—yet complex—behaviors such as cellular communication, responsiveness to environmental cues, and motility remain a challenge, yet to be resolved. Herein, recent efforts toward utilizing soft systems for cellular mimicry are summarized—following the main outline of cellular evolution, from basic compartmentalization, and biological reactions for energy production, to motility and communicative behaviors between artificial cell communities or between artificial and natural cell communities. Finally, the current challenges and future perspectives in the field are discussed, hoping to inspire more future research and to help the further advancement of this field.     

Plasmonic‐Based Mechanochromic Microcapsules as Strain Sensors

Efficiently detecting mechanical deformations within materials is critical in a wide range of devices, from micro‐electromechanical systems to larger structures in the aerospace industry. This communication reports the fabrication of new mechanochromic micrometer‐size capsules enabling the detection of strains. These microcapsules are synthesized using an emulsification approach. They are made of densely packed gold nanoparticles embedded in a spherical silica crust. Billions of these composite spherical microcapsules are fabricated in a single batch. Each microcapsule is an opto‐mechanosensor by itself, and can easily be recovered and incorporated into polymer films. When the films are stretched, the microcapsules are deformed into elongated ellipsoidal shapes and the distance between the Au NPs embedded in their shells concomitantly increases. As the extinction of Au NPs depends on the separation between the Au NPs, microcapsules exhibit different colors when they are elongated. These novel sensitive microcapsules can be used to detect and measure strain in polymer films by outputting color information.     

Coordinated Membrane Fusion of Proteinosomes by Contact‐Induced Hydrogel Self‐Healing

Controlled membrane fusion of proteinosome‐based protocells is achieved via a hydrogel‐mediated process involving dynamic covalent binding, self‐healing, and membrane reconfiguration at the contact interface. The rate of proteinosome fusion is dependent on dynamic Schiff base covalent interchange, and is accelerated in the presence of encapsulated glucose oxidase and glucose, or inhibited with cinnamyl aldehyde due to enzyme‐mediated decreases in pH or competitive covalent binding, respectively. The coordinated fusion of the proteinosomes leads to the concomitant transportation and redistribution of entrapped payloads such as DNA and dextran. Silica colloids with amino‐functionalized surfaces undergo partial fusion with the proteinosomes via a similar dynamic hydrogel‐mediated mechanism. Overall, the strategy provides opportunities for the development of interacting colloidal objects, control of collective behavior in soft matter microcompartmentalized systems, and increased complexity in synthetic protocell communities.     

Catechol‐Based Biomimetic Functional Materials

Catechols are found in nature taking part in a remarkably broad scope of biochemical processes and functions. Though not exclusively, such versatility may be traced back to several properties uniquely found together in the o‐dihydroxyaryl chemical function; namely, its ability to establish reversible equilibria at moderate redox potentials and pHs and to irreversibly cross‐link through complex oxidation mechanisms; its excellent chelating properties, greatly exemplified by, but by no means exclusive, to the binding of Fe³⁺; and the diverse modes of interaction of the vicinal hydroxyl groups with all kinds of surfaces of remarkably different chemical and physical nature. Thanks to this diversity, catechols can be found either as simple molecular systems, forming part of supramolacular structures, coordinated to different metal ions or as macromolecules mostly arising from polymerization mechanisms through covalent bonds. Such versatility has allowed catechols to participate in several natural processes and functions that range from the adhesive properties of marine organisms to the storage of some transition metal ions. As a result of such an astonishing range of functionalities, catechol‐based systems have in recent years been subject to intense research, aimed at mimicking these natural systems in order to develop new functional materials and coatings. A comprehensive review of these studies is discussed in this paper.     

Superwettability‐Based Interfacial Chemical Reactions

Superwetting interfaces arising from the cooperation of surface energy and multiscale micro/nanostructures are extensively studied in biological systems. Fundamental understandings gained from biological interfaces boost the control of wettability under different dimensionalities, such as 2D surfaces, 1D fibers and channels, and 3D architectures, thus permitting manipulation of the transport physics of liquids, gases, and ions, which profoundly impacts chemical reactions and material fabrication. In this context, the progress of new chemistry based on superwetting interfaces is highlighted, beginning with mass transport dynamics, including liquid, gas, and ion transport. In the following sections, the impacts of the superwettability‐mediated transport dynamics on chemical reactions and material fabrication is discussed. Superwettability science has greatly enhanced the efficiency of chemical reactions, including photocatalytic, bioelectronic, electrochemical, and organic catalytic reactions, by realizing efficient mass transport. For material fabrication, superwetting interfaces are pivotal in the manipulation of the transport and microfluidic dynamics of liquids on solid surfaces, leading to the spatially regulated growth of low‐dimensional single‐crystalline arrays and high‐quality polymer films. Finally, a perspective on future directions is presented.     

Smart Microcapsules with Molecular Polarity‐ and Temperature‐Dependent Permeability

Microcapsules with molecule‐selective permeation are appealing as microreactors, capsule‐type sensors, drug and cell carriers, and artificial cells. To accomplish molecular size‐ and charge‐selective permeation, regular size of pores and surface charges have been formed in the membranes. However, it remains an important challenge to provide advanced regulation of transmembrane transport. Here, smart microcapsules are designed that provide molecular polarity‐ and temperature‐dependent permeability. With capillary microfluidic devices, water‐in‐oil‐in‐water (W/O/W) double‐emulsion drops are prepared, which serve as templates to produce microcapsules. The oil shell is composed of two monomers and dodecanol, which turns to a polymeric framework whose continuous voids are filled with dodecanol upon photopolymerization. One of the monomers provides mechanical stability of the framework, whereas the other serves as a compatibilizer between growing polymer and dodecanol, preventing macrophase separation. Above melting point of dodecanol, molecules that are soluble in the molten dodecanol are selectively allowed to diffuse across the shell, where the rate of transmembrane transport is strongly influenced by partition coefficient. The rate is drastically lowered for temperatures below the melting point. This molecular polarity‐ and temperature‐dependent permeability renders the microcapsules potentially useful as drug carriers for triggered release and contamination‐free microreactors and microsensors.     

Bio‐Inspired,Self‐Toughening Polymers Enabled by Plasticizer‐Releasing Microcapsules

A new concept for the design of self‐toughening thermoplastic polymers is presented. The approach involves the incorporation of plasticizer‐filled microcapsules (MCs) in an intrinsically rigid and brittle matrix polymer. The intriguing adaptability that this simple tactic enables is demonstrated with composites composed of a poly(lactic acid) (PLA) matrix and 5–20% w/w poly(urea‐formaldehyde) (PUF) MCs that contained hexyl acetate as plasticizer. At low strain (<1.5%), the glassy PLA/MC composites remain rigid, although the intact MCs reduce the Young's modulus and tensile strength by up to 50%. While the neat PLA shows brittle failure at a strain of around 2.5%, the composites yield in this regime, because the MCs rupture and release their plasticizing cargo. This effect leads up to 25‐fold increase of the elongation at break and 20‐fold increase of the toughness vis‐à‐vis the neat PLA, while the impact on modulus and ultimate stress is much smaller. Ballistic impact tests show that the self‐toughening mechanism also works at much higher strain rates than applied in tensile tests and the operating mechanism is corroborated through systematic thermomechanical studies that involved dynamic mechanical testing and thermal analysis.