Life-like Materials Research Articles

Mechano-adaptive meta-gels through synergistic chemical and physical information-processing

Global functional adaptation after local mechanical stimulation, as in mechanobiology and the mimosa plant, is fascinating and ubiquitous in nature. This is achieved by locally sensing mechanical deformation with precise thresholds, processing this information via biochemical circuits, followed by downstream actuation. The integration of such embodied intelligence allowing for mechano-to-chemo-to-function information-processing remains elusive in man-made systems. By merging the fields of chemical circuits and metamaterials, we introduce adaptive metamaterial hydrogels (meta-gels) that can accurately sense mechanical stimuli (local touch and global strain), transmit this information over long distances via reaction-diffusion signaling, and induce downstream mechanical strengthening by growing nanofibril networks, or soft robotic actuation through competitive swelling. All elements of the sensor-processor-actuator system are embedded in the device, functioning autonomously without external feeding reservoirs. Our concept enables designing advanced life-like materials systems that synergistically combine two worlds – chemical circuits for chemical information-processing and metamaterial unit cells for physical information-processing.

Mechanistic Insights into Curvature Formation in Synthetic Vesicles.

The mimicking of natural lipid bilayers with synthetic amphiphilic systems is of great interest to researchers, as insights could lead to better understanding of the complexities of cell membranes, as well as new materials and healthcare technologies. Recapitulating natural lipid asymmetry across bilayer membranes has important implications for curvature in cell, vesicle, and organelle morphologies, but has been challenging to achieve with synthetic lipid combinations or standard amphiphilic block copolymers. In a recent article, Elizebath et al. report the synthesis of a new type of synthetic amphiphile able to induce asymmetry in an artificial bilayer membrane dynamically. The molecules were designed around an extended π-conjugated hydrophobic core with tertiary amine-terminated oxyalkylene side chains. Protonation of the tertiary amines on the bilayer exterior leads to curvature induction, bilayer fission, and vesicle formation as monitored by time-resolved spectroscopy techniques and microscopy. The results were further validated with density functional theory (DFT) calculations. The delicate balance between different molecular scale interactions in the supramolecular structures led to the dynamic transformation of the bilayer membranes. Insights described could be used to advance the assembly of hierarchical life-like materials.

Non-Equilibrium Assembly of Atomically-Precise Copper Nanoclusters.

Accurate structure control in dissipative assemblies (DSAs) is vital for precise biological functions. However, accuracy and functionality of artificial DSAs are far from this objective. Herein, a novel approach is introduced by harnessing complex chemical reaction networks rooted in coordination chemistry to create atomically-precise copper nanoclusters (CuNCs), specifically Cu11(µ9-Cl)(µ3-Cl)3L6Cl (L = 4-methyl-piperazine-1-carbodithioate). Cu(I)-ligand ratio change and dynamic Cu(I)-Cu(I) metallophilic/coordination interactions enable the reorganization of CuNCs into metastable CuL2, finally converting into equilibrium [CuL·Y]Cl (Y = MeCN/H2O) via Cu(I) oxidation/reorganization and ligand exchange process. Upon adding ascorbic acid (AA), the system goes further dissipative cycles. It is observed that the encapsulated/bridging halide ions exert subtle influence on the optical properties of CuNCs and topological changes of polymeric networks when integrating CuNCs as crosslink sites. CuNCs duration/switch period could be controlled by varying the ions, AA concentration, O2 pressure and pH. Cu(I)-Cu(I) metallophilic and coordination interactions provide a versatile toolbox for designing delicate life-like materials, paving the way for DSAs with precise structures and functionalities. Furthermore, CuNCs can be employed as modular units within polymers for materials mechanics or functionalization studies.

Dynamic Growth of Macroscopically Structured Supramolecular Hydrogels through Orchestrated Reaction-Diffusion.

Living organisms are capable of dynamically changing their structures for adaptive functions through sophisticated reaction-diffusion processes. Here we show how active supramolecular hydrogels with programmable lifetimes and macroscopic structures can be created by relying on a simple reaction-diffusion strategy. Two hydrogel precursors (poly(acrylic acid) PAA/CaCl2 and Na2 CO3 ) diffuse from different locations and generate amorphous calcium carbonate (ACC) nanoparticles at the diffusional fronts, leading to the formation of hydrogel structures driven by electrostatic interactions between PAA and ACC nanoparticles. Interestingly, the formed hydrogels are capable of autonomously disintegrating over time because of a delayed influx of electrostatic-interaction inhibitors (NaCl). The hydrogel growth process is well explained by a reaction-diffusion model which offers a theoretical means to program the dynamic growth of structured hydrogels. Furthermore, we demonstrate a conceptual access to dynamic information storage in soft materials using the developed reaction-diffusion strategy. This work may serve as a starting point for the development of life-like materials with adaptive structures and functionalities.

How Smart are Smart Materials? A Conceptual and Ethical Analysis of Smart Lifelike Materials for the Design of Regenerative Valve Implants.

It may soon become possible not just to replace, but to re-grow healthy tissues after injury or disease, because of innovations in the field of Regenerative Medicine. One particularly promising innovation is a regenerative valve implant to treat people with heart valve disease. These implants are fabricated from so-called 'smart', 'lifelike' materials. Implanted inside a heart, these implants stimulate re-growth of a healthy, living heart valve. While the technological development advances, the ethical implications of this new technology are still unclear and a clear conceptual understanding of the notions 'smart' and 'lifelike' is currently lacking. In this paper, we explore the conceptual and ethical implications of the development of smart lifelike materials for the design of regenerative implants, by analysing heart valve implants as a showcase. In our conceptual analysis, we show that the materials are considered 'smart' because they can communicate with human tissues, and 'lifelike' because they are structurally similar to these tissues. This shows that regenerative valve implants become intimately integrated in the living tissues of the human body. As such, they manifest the ontological entanglement of body and technology. In our ethical analysis, we argue this is ethically significant in at least two ways: It exacerbates the irreversibility of the implantation procedure, and it might affect the embodied experience of the implant recipient. With our conceptual and ethical analysis, we aim to contribute to responsible development of smart lifelike materials and regenerative implants.

Lifelike Transformative Materials for Biohybrid Implants: Inspired by Nature, Driven by Technology.

Today's living world is enriched with a myriad of natural biological designs, shaped by billions of years of evolution. Unraveling the construction rules of living organisms offers the potential to create new materials and systems for biomedicine. From the close examination of living organisms, several concepts emerge: hierarchy, pattern repetition, adaptation, and irreducible complexity. All these aspects must be tackled to develop transformative materials with lifelike behavior. This perspective article highlights recent progress in the development of transformative biohybrid systems for applications in the fields of tissue regeneration and biomedicine. Advances in computational simulations and data-driven predictions are also discussed. These tools enable the virtual high-throughput screening of implant design and performance before committing to fabrication, thus reducing the development time and cost of biomimetic and biohybrid constructs. The ongoing progress of imaging methods also constitutes an essential part of this matter in order to validate the computation models and enable longitudinal monitoring. Finally, the current challenges of lifelike biohybrid materials, including reproducibility, ethical considerations, and translation, are discussed. Advances in the development of lifelike materials will open new biomedical horizons, where perhaps what is currently envisioned as science fiction will become a science-driven reality in the future.

Selective control of donor-acceptor Stenhouse adduct populations with non-selective stimuli

Selective control of donor-acceptor Stenhouse adduct populations with non-selective stimuli

Adaptive 2D and Pseudo-2D Systems: Molecular, Polymeric, and Colloidal Building Blocks for Tailored Complexity.

Two-dimensional and pseudo-2D systems come in various forms. Membranes separating protocells from the environment were necessary for life to occur. Later, compartmentalization allowed for the development of more complex cellular structures. Nowadays, 2D materials (e.g., graphene, molybdenum disulfide) are revolutionizing the smart materials industry. Surface engineering allows for novel functionalities, as only a limited number of bulk materials have the desired surface properties. This is realized via physical treatment (e.g., plasma treatment, rubbing), chemical modifications, thin film deposition (using both chemical and physical methods), doping and formulation of composites, or coating. However, artificial systems are usually static. Nature creates dynamic and responsive structures, which facilitates the formation of complex systems. The challenge of nanotechnology, physical chemistry, and materials science is to develop artificial adaptive systems. Dynamic 2D and pseudo-2D designs are needed for future developments of life-like materials and networked chemical systems in which the sequences of the stimuli would control the consecutive stages of the given process. This is crucial to achieving versatility, improved performance, energy efficiency, and sustainability. Here, we review the advancements in studies on adaptive, responsive, dynamic, and out-of-equilibrium 2D and pseudo-2D systems composed of molecules, polymers, and nano/microparticles.

Weak catch bonds make strong networks.

Molecular catch bonds are ubiquitous in biology and essential for processes like leukocyte extravasion1 and cellular mechanosensing2. Unlike normal (slip) bonds, catch bonds strengthen under tension. The current paradigm is that this feature provides ’strength-on-demand’3, thus enabling cells to increase rigidity under stress1,4,5,6. However, catch bonds are often weaker than slip bonds because they have cryptic binding sites that are usually buried7,8. Here we show that catch bonds render reconstituted cytoskeletal actin networks stronger than slip bonds, even though the individual bonds are weaker. Simulations show that slip bonds remain trapped in stress-free areas, whereas weak binding allows catch bonds to mitigate crack initiation by moving to high-tension areas. This ‘dissociation-on-demand’ explains how cells combine mechanical strength with the adaptability required for shape change, and is relevant to diseases where catch bonding is compromised7,9, including focal segmental glomerulosclerosis10 caused by the α-actinin-4 mutant studied here. We surmise that catch bonds are key to creating life-like materials.

Building programmable multicompartment artificial cells incorporating remotely activated protein channels using microfluidics and acoustic levitation

Intracellular compartments are functional units that support the metabolism within living cells, through spatiotemporal regulation of chemical reactions and biological processes. Consequently, as a step forward in the bottom-up creation of artificial cells, building analogous intracellular architectures is essential for the expansion of cell-mimicking functionality. Herein, we report the development of a droplet laboratory platform to engineer complex emulsion-based, multicompartment artificial cells, using microfluidics and acoustic levitation. Such levitated models provide free-standing, dynamic, definable droplet networks for the compartmentalisation of chemical species. Equally, they can be remotely operated with pneumatic, heating, and magnetic elements for post-processing, including the incorporation of membrane proteins; alpha-hemolysin; and mechanosensitive channel of large-conductance. The assembly of droplet networks is three-dimensionally patterned with fluidic input configurations determining droplet contents and connectivity, whilst acoustic manipulation can be harnessed to reconfigure the droplet network in situ. The mechanosensitive channel can be repeatedly activated and deactivated in the levitated artificial cell by the application of acoustic and magnetic fields to modulate membrane tension on demand. This offers possibilities beyond one-time chemically mediated activation to provide repeated, non-contact, control of membrane protein function. Collectively, this expands our growing capability to program and operate increasingly sophisticated artificial cells as life-like materials.

Dual-Driven Mechanically and Tribologically Adaptive Hydrogels Solely Constituted of Graphene Oxide and Water.

Although mythologies and fictions have recorded living creatures fully composed of inorganics, it is however hard to turn inorganic constituents into lifelike materials in reality as they usually do not possess characteristics required for constructing a living organism. Here, we report to our knowledge the first biomimetic hydrogel in response to both pH and temperature variations that solely comprises graphene oxide and water. The hydrogel is capable of abruptly and reversibly switching its mechanical and tribological properties by more than 10-fold and 5-fold magnitudes, respectively, as a result of pH- and/or thermal-induced topological reconfiguration of its internal microstructure and ordering. Such behavior closely mimics some natural living organisms such as muscles and sea cucumbers. The hydrogel also shows a low coefficient of friction at pH 2 and room temperature, indicating it a potent smart lubricant free of any flammable and toxic organic base oils and additives.

Who’s gonna use this? Acceptance prediction of emerging technologies with Cognitive-Affective Mapping and transdisciplinary considerations in the Anthropocene

In the Anthropocene, mankind is facing enormous challenges. Science and technology obviously have an essential role to play in addressing these challenges but have to be supplemented by the collaboration of different actors from the scientific and non-scientific community. Possibly beneficial technologies can only unfold their full potential if they are socially accepted. Participation and transdisciplinarity are key concepts in this regard. The need for methods fostering collaborative knowledge production and reverse communication from the public to the scientific community is accordingly high. In this article, we propose to apply Cognitive-Affective Mapping (CAM) to predict psychological acceptance of novel research fields and potentially resulting technologies. As an example, we use life-like materials systems. CAM enables acceptance prediction at an early stage—already for basic research when prototypes are not yet available. The method bridges the gap between qualitative and quantitative research traditions. Its product—Cognitive-Affective Maps (CAMs)—is a vivid visual tool. In perspective, CAM-based technology acceptance assessment can be conceived as a participatory, transdisciplinary practice.

Dissipative Organization of DNA Oligomers for Transient Catalytic Function.

The development of synthetic non‐equilibrium systems opens doors for man‐made life‐like materials. Yet, creating distinct transient functions from artificial fuel‐driven structures remains a challenge. Building on our ATP‐driven dynamic covalent DNA assembly in an enzymatic reaction network of concurrent ATP‐powered ligation and restriction, we introduce ATP‐fueled transient organization of functional subunits for various functions. The programmability of the ligation/restriction site allows to precisely organize multiple sticky‐end‐encoded oligo segments into double‐stranded (ds) DNA complexes. We demonstrate principles of ATP‐driven organization into sequence‐defined oligomers by sensing barcode‐embedded targets with different defects. Furthermore, ATP‐fueled DNAzymes for substrate cleavage are achieved by transiently ligating two DNAzyme subunits into a dsDNA complex, rendering ATP‐fueled transient catalytic function.

DNA-Controlled Spatiotemporal Patterning of a Cytoskeletal Active Gel.

Living cells move and change their shape because signaling chemical reactions modify the state of their cytoskeleton, an active gel that converts chemical energy into mechanical forces. To create life-like materials, it is thus key to engineer chemical pathways that drive active gels. Here we describe the preparation of DNA-responsive surfaces that control the activity of a cytoskeletal active gel composed of microtubules: A DNA signal triggers the release of molecular motors from the surface into the gel bulk, generating forces that structure the gel. Depending on the DNA sequence and concentration, the gel forms a periodic band pattern or contracts globally. Finally, we show that the structuration of the active gel can be spatially controlled in the presence of a gradient of DNA concentration. We anticipate that such DNA-controlled active matter will contribute to the development of life-like materials with self-shaping properties.

Self-healing Polymeric Hydrogels: Toward Multifunctional Soft Smart Materials

The concept of self-healing that involves a built-in ability to heal in response to damage wherever and whenever it occurs in a material, analogous to the healing process in living organisms, has emerged a couple of decades ago. Driven primarily by the demands for life-like materials and soft smart materials, therefore, the development of self-healing polymeric hydrogels has continually attracted scientific community. Here, this review is intended to give an in-depth overview of the state-of-the-art advances in self-healing polymeric hydrogels. Specifically, recently emerging trends in self-healing polymeric hydrogels are summarized, notably, recommendations to endow these hydrogels with fascinating multi-functionalities including luminescence, conductivity/magnetism and shape memory etc. are presented. To close, the current challenges and future opportunities within this field are also discussed.

Reversible Photoswitchable Inhibitors Generate Ultrasensitivity in Out-of-Equilibrium Enzymatic Reactions.

Ultrasensitivity is a ubiquitous emergent property of biochemical reaction networks. The design and construction of synthetic reaction networks exhibiting ultrasensitivity has been challenging, but would greatly expand the potential properties of life-like materials. Herein, we exploit a general and modular strategy to reversibly regulate the activity of enzymes using light and show how ultrasensitivity arises in simple out-of-equilibrium enzymatic systems upon incorporation of reversible photoswitchable inhibitors (PIs). Utilizing a chromophore/warhead strategy, PIs of the protease α-chymotrypsin were synthesized, which led to the discovery of inhibitors with large differences in inhibition constants (Ki) for the different photoisomers. A microfluidic flow setup was used to study enzymatic reactions under out-of-equilibrium conditions by continuous addition and removal of reagents. Upon irradiation of the continuously stirred tank reactor with different light pulse sequences, i.e., varying the pulse duration or frequency of UV and blue light irradiation, reversible switching between photoisomers resulted in ultrasensitive responses in enzymatic activity as well as frequency filtering of input signals. This general and modular strategy enables reversible and tunable control over the kinetic rates of individual enzyme-catalyzed reactions and makes a programmable linkage of enzymes to a wide range of network topologies feasible.

Opportunities and Challenges in DNA-Hybrid Nanomaterials.

Nature has inspired the development of many life-like materials. Although still simplistic, key biological functionalities have been incorporated, enabling a wide variety of applications. DNA-based systems, in particular, show high promise due to their ability to merge specific Watson-Crick base pairing with unique properties that are also programmable, scalable, or dynamic. By combining the fields of DNA-based covalent polymers, DNA origami, and DNA-functionalized supramolecular polymers, new frontiers in next-generation DNA-based hybrid materials that can outperform current bioartificial systems will be realized. Many challenges must still be overcome before this emerging technology can be materialized.

Lifelike materials show value of DNA as a polymer

Lifelike materials show value of DNA as a polymer

From mechanical resilience to active material properties in biopolymer networks

The cells and tissues that make up our body juggle contradictory mechanical demands. It is crucial for their survival to be able to withstand large mechanical loads, but it is equally crucial for them to produce forces and actively change shape during biological processes such as tissue growth and repair. The mechanics of cell and tissues is determined by scaffolds of protein polymers known as the cytoskeleton and the extracellular matrix, respectively. Experiments on model systems reconstituted from purified components combined with polymer physics concepts have already successfully uncovered some of the mechanisms that underlie the paradoxical mechanics of living matter. Initial work focussed on explaining universal features such as the nonlinear elasticity of cells and tissues in terms of polymer network models. However, living matter exhibits many advanced mechanical functionalities that are not captured by these coarse-grained theories. In this Review, we focus on recent experimental and theoretical insights revealing how their porous structure, structural hierarchy, transient crosslinking, and mechanochemical activity confer resilience combined with the ability to adapt and self-heal. These physical insights improve our understanding of cell and tissue biology and also provide a source of inspiration for synthetic life-like materials.

A chemically fuelled self-replicator

The continuous consumption of chemical energy powers biological systems so that they can operate functional supramolecular structures. A goal of modern science is to understand how simple chemical mixtures may transition from non-living components to truly emergent systems and the production of new lifelike materials and machines. In this work a replicator can be maintained out-of-equilibrium by the continuous consumption of chemical energy. The system is driven by the autocatalytic formation of a metastable surfactant whose breakdown products are converted back into building blocks by a chemical fuel. The consumption of fuel allows the high-energy replicators to persist at a steady state, much like a simple metabolic cycle. Thermodynamically-driven reactions effect a unidirectional substrate flux as the system tries to regain equilibrium. The metastable replicator persists at a higher concentration than achieved even transiently in a closed system, and its concentration is responsive to the rate of fuel supply.