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Marine mussels achieve strong underwater adhesion by depositing mussel foot proteins (Mfps) that form coacervates during the protein secretion. However, the molecular mechanisms that govern the phase separation behaviors of the Mfps are still not fully understood. Here, we report that GK-16*, a peptide derived from the primary adhesive protein Mfp-5, forms coacervate in seawater conditions. Molecular dynamics simulations combined with point mutation experiments demonstrate that Dopa- and Gly- mediated hydrogen-bonding interactions are essential in the coacervation process. The properties of GK-16* coacervates could be controlled by tuning the strength of the electrostatic and Dopa-mediated hydrogen bond interactions via controlling the pH and salt concentration of the solution. The GK-16* coacervate undergoes a pH induced liquid-to-gel transition, which can be utilized for the underwater delivery and curing of the adhesives. Our study provides useful molecular design principles for the development of mussel-inspired peptidyl coacervate adhesives with tunable properties. The phase separation in the coacervates of adhesive muscle foot proteins is not fully understood. Here, the authors use simulations and point mutations of a mussel foot derived protein to show that hydrogen bonding is essential in the formation of coacervates in sea water which can help develop underwater adhesives.

In the global sustainability drive, the role of water in the water-energy nexus is increasingly prominent due to the potential of passive evaporative cooling. However, the feasibility of evaporative cooling as a sustainable cooling alternative is currently limited by a lack of energy-efficient enhancement methods. Meanwhile, though electrostatic field-enhanced water evaporation has been widely documented, its underlying mechanism and impact on evaporative cooling remain unclear. Herein, we present experimental evidence establishing causality between electrostatic fields and evaporative cooling enhancement. We reveal two dominant factors at play, i.e., generation of ionic wind and tuning of vaporization enthalpy. The efficiency of the cooling enhancement method, when operating around the corona onset voltage, far exceeds that of conventional evaporative coolers. Similar cooling enhancements were also demonstrated on solid water within a hydrogel, showcasing its potential for practical applications. In addition, the electrostatic field reduces the vaporization enthalpy of solid water by altering the surface molecular arrangement, a finding corroborated through Raman spectroscopy. Besides elucidating cooling enhancement mechanisms, this study expands the toolkit for passive cooling solutions. Water has a role to play in the future of cooling but is currently limited by the lack of meaningful control methods. Here, authors demonstrate the ability of electrostatic fields to act as a catalyst for water-based evaporative cooling, paving the way for widescale adoption of evaporative cooling.

Membrane-damaging antimicrobial agents have great potential to treat multidrug-resistant or multidrug-tolerant bacteria against which conventional antibiotics are not effective. However, their therapeutic applications are often hampered due to their low selectivity to bacterial over mammalian membranes or their potential for cross-resistance to a broad spectrum of cationic membrane-active antimicrobial agents. We discovered that the diarylurea derivative compound PQ401 has antimicrobial potency against multidrug-resistant and multidrug-tolerant Staphylococcus aureus . PQ401 selectively disrupts bacterial membrane lipid bilayers in comparison to mammalian membranes. Unlike cationic membrane-active antimicrobials, the neutral form of PQ401 rather than its cationic form exhibits maximum membrane activity. Overall, our results demonstrate that PQ401 could be a promising lead compound that overcomes the current limitations of membrane selectivity and cross-resistance. Also, this work provides deeper insight into the design and development of new noncharged membrane-targeting therapeutics to combat hard-to-cure bacterial infections. Resistance or tolerance to traditional antibiotics is a challenging issue in antimicrobial chemotherapy. Moreover, traditional bactericidal antibiotics kill only actively growing bacterial cells, whereas nongrowing metabolically inactive cells are tolerant to and therefore “persist” in the presence of legacy antibiotics. Here, we report that the diarylurea derivative PQ401, previously characterized as an inhibitor of the insulin-like growth factor I receptor, kills both antibiotic-resistant and nongrowing antibiotic-tolerant methicillin-resistant Staphylococcus aureus (MRSA) by lipid bilayer disruption. PQ401 showed several beneficial properties as an antimicrobial lead compound, including rapid killing kinetics, low probability for resistance development, high selectivity to bacterial membranes compared to mammalian membranes, and synergism with gentamicin. In contrast to well-studied membrane-disrupting cationic antimicrobial low-molecular-weight compounds and peptides, molecular dynamic simulations supported by efficacy data demonstrate that the neutral form of PQ401 penetrates and subsequently embeds into bacterial lipid bilayers more effectively than the cationic form. Lastly, PQ401 showed efficacy in both the Caenorhabditis elegans and Galleria mellonella models of MRSA infection. These data suggest that PQ401 may be a lead candidate for repurposing as a membrane-active antimicrobial and has potential for further development as a human antibacterial therapeutic for difficult-to-treat infections caused by both drug-resistant and -tolerant S. aureus . IMPORTANCE Membrane-damaging antimicrobial agents have great potential to treat multidrug-resistant or multidrug-tolerant bacteria against which conventional antibiotics are not effective. However, their therapeutic applications are often hampered due to their low selectivity to bacterial over mammalian membranes or their potential for cross-resistance to a broad spectrum of cationic membrane-active antimicrobial agents. We discovered that the diarylurea derivative compound PQ401 has antimicrobial potency against multidrug-resistant and multidrug-tolerant Staphylococcus aureus . PQ401 selectively disrupts bacterial membrane lipid bilayers in comparison to mammalian membranes. Unlike cationic membrane-active antimicrobials, the neutral form of PQ401 rather than its cationic form exhibits maximum membrane activity. Overall, our results demonstrate that PQ401 could be a promising lead compound that overcomes the current limitations of membrane selectivity and cross-resistance. Also, this work provides deeper insight into the design and development of new noncharged membrane-targeting therapeutics to combat hard-to-cure bacterial infections.

Infections caused by Staphylococcus aureus, notably methicillin‐resistant S. aureus (MRSA), pose treatment challenges due to its ability to tolerate antibiotics and develop antibiotic resistance. The former, a mechanism independent of genetic changes, allows bacteria to withstand antibiotics by altering metabolic processes. Here, a potent methylazanediyl bisacetamide derivative, MB6, is described, which selectively targets MRSA membranes over mammalian membranes without observable resistance development. Although MB6 is effective against growing MRSA cells, its antimicrobial activity against MRSA persisters is limited. Nevertheless, MB6 significantly potentiates the bactericidal activity of gentamicin against MRSA persisters by facilitating gentamicin uptake. In addition, MB6 in combination with daptomycin exhibits enhanced anti‐persister activity through mutual reinforcement of their membrane‐disrupting activities. Crucially, the “triple” combination of MB6, gentamicin, and daptomycin exhibits a marked enhancement in the killing of MRSA persisters compared to individual components or any double combinations. These findings underscore the potential of MB6 to function as a potent and selective membrane‐active antimicrobial adjuvant to enhance the efficacy of existing antibiotics against persister cells. The molecular mechanisms of MB6 elucidated in this study provide valuable insights for designing anti‐persister adjuvants and for developing new antimicrobial combination strategies to overcome the current limitations of antibiotic treatments. This study presents MB6, a methylazanediyl bisacetamide derivative, as a potent antimicrobial agent selectively targeting MRSA membranes. MB6 demonstrates triple synergistic killing against MRSA persisters by promoting gentamicin uptake and enhancing the membrane‐disrupting activity of daptomycin. This positions MB6 as a promising adjuvant in combating antibiotic‐resistant and ‐tolerant infections, offering innovative strategies in antimicrobial treatments.

The interplay between vesicles and their enclosed filaments is fundamental to the morphogenesis, motility, and mechanical response of biological cells, artificial cells, and biomimetic robotic systems. By engineering responsiveness or interaction capabilities-such as long-range filament interactions-these filaments can function as active elements that regulate system behavior. Here, we combine theoretical modeling and molecular dynamics simulations to demonstrate how interacting filament loops within vesicles induce diverse, system-wide morphological transformations. These transformations are driven by inter- and intrafilament interactions, as well as the competing deformations of both the vesicle and its encapsulated filaments, with interfilament interactions playing a dominant role. We observe phenomena including filament buckling and reorientation, vesicle stretching, and convex-to-concave shape transitions. Morphological phase diagrams are constructed for both vesicles under zero osmotic pressure and those with a fixed relative volume, and we further explore the packing of inhomogeneous filament loops. These results offer quantitative design principles for artificial cellular systems in which filament interactions act as levers to control and stabilize emergent morphologies, laying the groundwork for the development of adaptive soft robotics.

The original version of this Article was incorrectly labelled as a ‘Review Article’. This has now been corrected to ‘Article’ in both the HTML and PDF versions.

Stretchable hybrid devices have enabled high-fidelity implantable 1 – 3 and on-skin 4 – 6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans 7 , 8 and soft robots 9 , 10 , rigid modules containing Si-based microelectronics 11 , 12 and protective encapsulation modules 13 , 14 . To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure 15 – 17 . Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft–soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm −1 . As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices. A universal interface connects soft, rigid and encapsulation modules together to form robust, stretchable devices in a plug-and-play manner by pressing without using pastes, which will simplify and accelerate development of on-skin and implantable devices.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue–electronics interfaces, however, cannot be standardized, because tissues are soft 1 – 3 and have arbitrary shapes and sizes 4 – 6 . Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated 7 . However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs.  8 , 9 ). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk 10 – 12 , we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue–electronics interfaces as well as broadening the biomedical application of shape-adaptive materials. Water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex contract by more than 50% of their original length within seconds after wetting and become soft and stretchable hydrogel thin films that can be used in bioelectronic interfaces.

Biological systems can create materials with intricate structures and specialized functions. In comparison, precise control of structures in human-made materials has been challenging. Here we report on insect cuticle peptides that spontaneously form nanocapsules through a single-step solvent exchange process, where the concentration gradient resulting from the mixing of water and acetone drives the localization and self-assembly of the peptides into hollow nanocapsules. The underlying driving force is found to be the intrinsic affinity of the peptides for a particular solvent concentration, while the diffusion of water and acetone creates a gradient interface that triggers peptide localization and self-assembly. This gradient-mediated self-assembly offers a transformative pathway towards simple generation of drug delivery systems based on peptide nanocapsules. Biobased materials are of interest for many applications. Here the authors report insect-derived peptides that self-assemble into hollow nanocapsules through a gradient-driven, single-step, solvent exchange process, enabling the encapsulation of diverse cargoes with potential for drug delivery applications.