Chemical tools and materials for Biological/Medicinal applications

Guest editors Xuehai Yan and Jan C. M. van Hest discuss in their editorial to this special issue recent advances in chemical tools and materials that have significantly promoted both preventive and therapeutic biomedicine, and highlight the the state‐of‐the‐art contributions in this research field featured in this special issue

Artificial cells: synthetic compartments with life-like functionality and adaptivity

Cells are highly advanced microreactors that form the basis of all life. Their fascinating complexity has inspired scientists to create analogs from synthetic and natural components using a bottom-up approach. The ultimate goal here is to assemble a fully man-made cell that displays functionality and adaptivity as advanced as that found in nature, which will not only provide insight into the fundamental processes in natural cells but also pave the way for new applications of such artificial cells.\u3cbr/\u3e\u3cbr/\u3eIn this Account, we highlight our recent work and that of others on the construction of artificial cells. First, we will introduce the key features that characterize a living system; next, we will discuss how these have been imitated in artificial cells. First, compartmentalization is crucial to separate the inner chemical milieu from the external environment. Current state-of-the-art artificial cells comprise subcompartments to mimic the hierarchical architecture of eukaryotic cells and tissue. Furthermore, synthetic gene circuits have been used to encode genetic information that creates complex behavior like pulses or feedback. Additionally, artificial cells have to reproduce to maintain a population. Controlled growth and fission of synthetic compartments have been demonstrated, but the extensive regulation of cell division in nature is still unmatched.\u3cbr/\u3e\u3cbr/\u3eHere, we also point out important challenges the field needs to overcome to realize its full potential. As artificial cells integrate increasing orders of functionality, maintaining a supporting metabolism that can regenerate key metabolites becomes crucial. Furthermore, life does not operate in isolation. Natural cells constantly sense their environment, exchange (chemical) signals, and can move toward a chemoattractant. Here, we specifically explore recent efforts to reproduce such adaptivity in artificial cells. For instance, synthetic compartments have been produced that can recruit proteins to the membrane upon an external stimulus or modulate their membrane composition and permeability to control their interaction with the environment. A next step would be the communication of artificial cells with either bacteria or another artificial cell. Indeed, examples of such primitive chemical signaling are presented. Finally, motility is important for many organisms and has, therefore, also been pursued in synthetic systems. Synthetic compartments that were designed to move in a directed, controlled manner have been assembled, and directed movement toward a chemical attractant is among one of the most life-like directions currently under research.\u3cbr/\u3e\u3cbr/\u3eAlthough the bottom-up construction of an artificial cell that can be truly considered “alive” is still an ambitious goal, the recent work discussed in this Account shows that this is an active field with contributions from diverse disciplines like materials chemistry and biochemistry. Notably, research during the past decade has already provided valuable insights into complex synthetic systems with life-like properties. In the future, artificial cells are thought to contribute to an increased understanding of processes in natural cells and provide opportunities to create smart, autonomous, cell-like materials.\u3cbr/\u3

Compartmentalization approaches in soft matter science: from nanoreactor development to organelle mimics

Compartmentalization is an essential feature found in living cells to ensure that biological processes occur without being affected by undesired external influences. Over the years many scientists have designed self-assembled soft matter structures that mimic these natural catalytic compartments. The rationale behind this research is threefold. First of all, compartmentalization leads to the creation of a secluded environment for the catalytic species, which solves compatibility issues and which can improve catalyst efficiency and selectivity. Secondly, nano- and micro-compartments are constructed with the aim to obtain microenvironments that more closely mimic the cellular architecture. These biomimetic platforms are used to attain a better understanding of how cellular processes are executed. Thirdly, natural design rules are applied to create biomolecular assemblies with unusual functionality, which for example are used as artificial organelles. Here, recent developments will be discussed regarding these compartmentalized catalytic systems, with a selected number of illustrative examples to demonstrate which strategies have been followed, and to show to what extent the ambitious goals of this field of science have been reached. The focus here is on the field of soft matter science, covering the wide spectrum from polymeric assemblies to protein nanocages

The hallmarks of living systems:Towards creating artificial cells

\u3cp\u3eDespite the astonishing diversity and complexity of living systems, they all share five common hallmarks: compartmentalization, growth and division, information processing, energy transduction and adaptability. In this review, we give not only examples of how cells satisfy these requirements for life and the ways in which it is possible to emulate these characteristics in engineered platforms, but also the gaps that remain to be bridged. The bottom-up synthesis of life-like systems continues to be driven forward by the advent of new technologies, by the discovery of biological phenomena through their transplantation to experimentally simpler constructs and by providing insights into one of the oldest questions posed by mankind, the origin of life on Earth.\u3c/p\u3

Feedback-induced temporal control of “breathing” polymersomes to create self-adaptive nanoreactors

\u3cbr/\u3e\u3cbr/\u3eHere we present the development of self-regulated “breathing” polymersome nanoreactors that show temporally programmable biocatalysis induced by a chemical fuel. pH-sensitive polymersomes loaded with horseradish peroxidase (HRP) and urease were developed. Addition of an acidic urea solution (“fuel”) endowed the polymersomes with a transient size increase and permeability enhancement, driving a temporal “ON” state of the HRP enzymatic catalysis; subsequent depletion of fuel led to shrinking of the polymersomes, resulting in the catalytic “OFF” state. Moreover, the nonequilibrium nanoreactors could be reinitiated several cycles as long as fuel was supplied. This feedback-induced temporal control of catalytic activity in polymersome nanoreactors provides a platform for functional nonequilibrium systems as well as for artificial organelles with precisely controlled adaptivity.\u3cbr/\u3

Self-regulated and temporal control of a breathing microgel mediated by enzymatic reaction

Naturally occurring systems have the ability to self-regulate, which plays a key role in their structural and functional adaptation. The autonomous behavior in living systems is biocatalytically controlled by the continuous consumption of energy to remain in a non-equilibrium condition. In this work, we show the construction of a self-regulated breathing microgel that uses chemical fuels to keep the system in the out-of-equilibrium state. The enzyme urease is utilized to program a feedback-induced pH change, which in turn tunes the size switch and fluorescence intensity of the microgel. A continuous supply of chemical fuels to the system allows the process to be reversible. This microgel with tunable autonomous properties provides insights into the design of artificial systems and dynamic soft materials

Reversibly triggered protein-ligand assemblies in giant vesicles

\u3cp\u3eExternal small-molecule triggers were used to reversibly control dynamic protein-ligand interactions in giant vesicles. An alcohol dehydrogenase was employed to increase or decrease the interior pH upon conversion of two different small-molecule substrates, thereby modulating the pH-sensitive interaction between a Ni-NTA ligand on the vesicle membrane and an oligohistidine-tagged protein in the lumen. By alternating the small-molecule substrates the interaction could be reversed.\u3c/p\u3

Surface plasmon resonance (SPR) sensors for detecting allergens in food

\u3cp\u3eFood allergy is a growing public health concern. Patients suffering from food allergies need to avoid the offending food in order to avoid getting an allergic response. There is a need for a quick, cheap and reliable point-of-care (POC) sensor for household use and for industry use. Surface plasmon resonance (SPR) is an upcoming technique in the food allergen field. It has shown great potential for studying biomolecular interactions without extensive sample preparations such as the removal of excess reactants in sample solutions. Food sample preparation will be reduced to a minimum. Furthermore, this method is very sensitive and able to detect also trace amounts of food allergens.\u3c/p\u3

Morphology under control: engineering biodegradable stomatocytes

Biodegradable nanoarchitectures, with well-defined morphological features, are of great importance for nanomedical research; however, understanding (and thereby engineering) their formation is a substantial challenge. Herein, we uncover the supramolecular potential of PEG-PDLLA copolymers by exploring the physicochemical determinants that result in the transformation of spherical polymersomes into stomatocytes. To this end, we have engineered blended polymersomes (comprising copolymers with varying lengths of PEG), which undergo solvent-dependent reorganization inducing negative spontaneous membrane curvature. Under conditions of anisotropic solvent composition across the PDLLA membrane, facilitated by the dialysis methodology, we demonstrate osmotically induced stomatocyte formation as a consequence of changes in PEG solvation, inducing negative spontaneous membrane curvature. Controlled formation of unprecedented, biodegradable stomatocytes represents the unification of supramolecular engineering with the theoretical understanding of shape transformation phenomena