The Front Cover shows collections of communicating synthetic cells composed of water-in-oil droplets separated and stabilized by lipid bilayer interfaces and containing cell-free expression system with quorum sensing gene circuits. Cover design by David T. Gonzales. More information can be found in the Research Article by T.-Y. Dora Tang and co-worker.
The Cover Feature illustrates three strategies for the generation of dynamic combinatorial libraries (DCLs) of peptide or peptidomimetic-based assemblies. Exploring their self-adaptative potential can lead to the discovery of smart nanomaterials, drug nanocarriers or drugs for untreated diseases. Cover design by Ashmi Rodrigues. More information can be found in the Review by Ashmi Rodrigues, Lou Rocard and Roba Moumné.
This Concept highlights and reviews the progress made in the construction of hierarchically organized cell-mimics using droplet-based microfluidics methods. By exploiting the versatility and precision of droplet-based microfluidics, it has become possible to routinely produce well-defined cell-like systems. This technology has opened the door to the development of sophisticated adaptive cell mimics and bioreactors.
In recent years, there has been a growing interest in multi-compartment systems as a means of developing materials that mimic the structure and function of biological cells. These hierarchical systems, including artificial cells and cell-like reactors, can efficiently perform biochemical tasks by exploiting compartmentalization inspired by biological systems. However, the bottom-up design of cell mimics presents significant challenges due to the need for precise and efficient assembly of components. This short review examines recent advances in droplet-based microfluidics (DBM), which has emerged as a powerful technique for creating cell-like systems with multi-compartment architectures, precise composition, and biomimetic functionality. DBM has proven to be a reliable method for generating populations of cell-mimics with a compartment-in-compartment structure, some of which have adaptable properties that resemble the dynamic properties of natural cells. Notable examples will be discussed to illustrate how droplet-based microfluidics provides a versatile approach to create, manipulate, and study cell-mimics.
The RNA World theory for the origin of life requires polymers to be generated initially by abiotic reactions. Experiments have studied polymerization of 5′-monophosphates, 2′,3′-cyclic phosphates, and 5′-triphosphates. We consider theoretical models of polymerization in solution illustrating the differences between these cases. We consider (i) a basic model where all monomers undergo reversible joining and breaking; (ii) a model where 2′,3′-cyclic phosphates can join, and breaking regenerates the cyclic phosphate; (iii) a model where 5′-triphosphates can join irreversibly, in addition to the joining and breaking of 2′,3′-cyclic phosphates. In cases (i) and (ii) there is an equilibrium steady state with balance between making and breaking bonds. In case (iii) there is a circular reaction flux in which monomers are activated by an external phosphate source, activated monomers form polymers, and polymers break to release non-activated monomers. The mean length can be calculated as a function of concentration. In case (iii), the mean length switches from a low-concentration regime controlled by the 5′-triphosphates to a high-concentration regime controlled by the 2′,3′-cyclic phosphates. The circular reaction flux is reminiscent of a metabolism. If formation of 5’-triphosphates was already in place for RNA synthesis, ATP could subsequently been co-opted for metabolism.
“We show how recurring environmental constraints on ancient earth, namely cycles of freezing and thawing, might have driven the dissemination of genetic material in populations of primitive protocells. In this work, confocal fluorescence microscopy at sub-zero temperatures was used to gain mechanistic insights into inter-protocellular communication based on cyclic freezing and melting of the aqueous environment. The cover design highlights the transient formation of membrane pores that enable content diffusion across protocell membranes…” This and more about the story behind the front cover can be found in the Research Article at 10.1002/syst.202300008.
The front cover artwork is provided by the Schwille group from the Max Planck Institute of Biochemistry in Martinsried. The image shows the dissemination of genetic material in a population of primitive protocells during freeze-thaw induced periods of membrane permeability. Read the full text of the Research Article at 10.1002/syst.202300008.
The recognition of carbohydrates has been of growing interest in the supramolecular chemistry field, with specific relevance for numerous potential applications. At the same time, the binding many of carbohydrates in water selectively and with high affinity still presents a number of practical challenges that inspire ongoing research efforts toward new classes of bio-inspired synthetic receptors.
Carbohydrates play a number of structural, functional, and metabolic roles in underpinning natural life processes, acting in states of both health and disease. Given this importance, over millions of years of evolution, living systems have developed an ability to recognize and bind carbohydrates, achieving remarkable recognition affinity and specificity in spite of the often hydrophilic and ubiquitous character of carbohydrate targets. In recent years, bio-inspired synthetic receptors have been developed to bind carbohydrates, with examples of (pseudo)temple-shaped receptors, flexible receptors, and dynamic-covalent/coordinative receptors reported. Certain of these have even demonstrated promising results, for example in binding glucose or exhibiting antiviral and antibiotic function. Accordingly, and in spite of remaining challenges, the development of synthetic receptors for carbohydrate recognition holds great promise to combat some of the most urgent problems facing our world today.
The Front Cover illustrates the exchange of genetic material between model protocells through cycles of freezing and thawing. Freeze-thaw cycles as prebiotic environmental driver induce a transient increase in membrane permeability enabling the lateral transfer of genetic information in a population of primitive protocells. More information can be found in the Research Article by Benedikt Peter and Petra Schwille.
Glass composition matters: This work demonstrates that the outcome of dry-phase prebiotic polymerization reactions could have been strongly affected by the oxide composition of the hosting rock glasses.
Silicate glasses are ubiquitous on terrestrial planets wherever molten rock – generated by volcanism or impacts – is quenched by air or water. Hence, they provided ready and abundant reactive solid surfaces for prebiotic chemistry on the early Earth. Here, we show that rock glass composition determines basicity, which in turn modulates the outcome of prebiotic synthetic processes such as the polymerization of 3’, 5’ cyclic guanosine monophosphate.
Freeze-thaw cycles serve as physicochemical driving force for the lateral exchange of enclosed material between giant lipid vesicles. It was demonstrated that this exchange relies on transient periods of membrane permeability leading to content diffusion across vesicle membranes. Moreover, we explored and quantified essential parameters affecting the lateral transfer efficiency.
Modern cells rely on highly evolved protein networks to accomplish essential life functions, including the inheritance of information from parents to their offspring. In the absence of these sophisticated molecular machineries, alternatives were required for primitive protocells to proliferate and disseminate genetic material. Recurring environmental constraints on ancient earth, such as temperature cycles, are considered as prebiotically plausible driving forces capable of shuffling of protocellular contents, thereby boosting compositional complexity. Using confocal fluorescence microscopy, we show that temperature oscillations such as freezing-thawing (FT) cycles promote efficient content mixing between giant unilamellar vesicles (GUVs) as model protocells. We shed light on the underlying exchange mechanism and demonstrate that transient periods of destabilized membranes enable the diffusion of cargo molecules across vesicle membranes. Furthermore, we determine essential parameters, such as membrane composition, and quantify their impact on the lateral transfer efficiency. Our work outlines a simple scenario revolving around inter-protocellular communication environmentally driven by periodic freezing and melting of water.
Function in RNA oligomers - specifically low μM specific binding of purine (ATP and GTP) nucleotides - can arise from single, non-functional and partially homopolymeric (polyA) sequences of minimal structural and informational complexity by iterative cycles of mutation and selection.
The spontaneous emergence of function from diverse RNA sequence pools is widely considered an important transition in the origin of life. Here we show that diverse sequence pools are not a prerequisite for the emergence of function. Starting five independent selection experiments each from a single RNA seed sequence - comprising a central homopolymeric poly-A (or poly-U) segment flanked by different conserved primer binding sites - we observe transformation (continuous drift) of the seeds into low diversity sequence pools by mutation, truncation and recombination without ever reaching that of a random pool even after 24 rounds. Upon continuous error prone replication and selection for ATP binding we isolate specific ATP- or GTP-binding aptamers with low micromolar affinities. Our results have implications for early RNA evolution in the light of the high mutation rates associated with both non-enzymatic and enzymatic prebiotic RNA replication.