Microporous water with high gas solubilities.

Liquids with permanent microporosity can absorb larger quantities of gas molecules than conventional solvents1, providing new opportunities for liquid-phase gas storage, transport and reactivity. Current approaches to designing porous liquids rely on sterically bulky solvent molecules or surface ligands and, thus, are not amenable to many important solvents, including water2-4. Here we report a generalizable thermodynamic strategy to preserve permanent microporosity and impart high gas solubilities to liquid water. Specifically, we show how the external and internal surface chemistry of microporous zeolite and metal-organic framework (MOF) nanocrystals can be tailored to promote the formation of stable dispersions in water while maintaining dry networks of micropores that are accessible to gas molecules. As a result of their permanent microporosity, these aqueous fluids can concentrate gases, including oxygen (O2) and carbon dioxide (CO2), to much higher densities than are found in typical aqueous environments. When these fluids are oxygenated, record-high capacities of O2 can be delivered to hypoxic red blood cells, highlighting one potential application of this new class of microporous liquids for physiological gas transport.

Reexpansion of charged nanoparticle assemblies in concentrated electrolytes.

Electrostatic forces in solutions are highly relevant to a variety of fields, ranging from electrochemical energy storage to biology. However, their manifestation in concentrated electrolytes is not fully understood, as exemplified by counterintuitive observations of colloidal stability and long-ranged repulsions in molten salts. Highly charged biomolecules, such as DNA, respond sensitively to ions in dilute solutions. Here, we use non-base-pairing DNA-coated nanoparticles (DNA-NP) to analyze electrostatic interactions in concentrated salt solutions. Despite their negative charge, these conjugates form colloidal crystals in solutions of sufficient divalent cation concentration. We utilize small-angle X-ray scattering (SAXS) to study such DNA-NP assemblies across the full accessible concentration ranges of aqueous CaCl2, MgCl2, and SrCl2 solutions. SAXS shows that the crystallinity and phases of the assembled structures vary with cation type. For all tested salts, the aggregates contract with added ions at low salinities and then begin expanding above a cation-dependent threshold salt concentration. Wide-angle X-ray scattering (WAXS) reveals enhanced positional correlations between ions in the solution at high salt concentrations. Complementary molecular dynamics simulations show that these ion-ion interactions reduce the favorability of dense ion configurations within the DNA brushes below that of the bulk solution. Measurements in solutions with lowered permittivity demonstrate a simultaneous increase in ion coupling and decrease in the concentration at which aggregate expansion begins, thus confirming the connection between these phenomena. Our work demonstrates that interactions between charged objects continue to evolve considerably into the high-concentration regime, where classical theories project electrostatics to be of negligible consequence.

Single-chain heteropolymers transport protons selectively and rapidly.

Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels1,2, both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks3-13. However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)14 can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains15,16 for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.

Colloidal superionic conductors.

Nanoparticles with highly asymmetric sizes and charges that self-assemble into crystals via electrostatics may exhibit behaviors reminiscent of those of metals or superionic materials. Here, we use coarse-grained molecular simulations with underdamped Langevin dynamics to explore how a binary charged colloidal crystal reacts to an external electric field. As the field strength increases, we find transitions from insulator (ionic state), to superionic (conductive state), to laning, to complete melting (liquid state). In the superionic state, the resistivity decreases with increasing temperature, which is contrary to metals, yet the increment decreases as the electric field becomes stronger. Additionally, we verify that the dissipation of the system and the fluctuation of charge currents obey recently developed thermodynamic uncertainty relation. Our results describe charge transport mechanisms in colloidal superionic conductors.

PDZ scaffolds regulate extracellular vesicle production, composition, and uptake.

Extracellular vesicles (EVs) are membrane-limited organelles mediating cell-to-cell communication in health and disease. EVs are of high medical interest, but their rational use for diagnostics or therapies is restricted by our limited understanding of the molecular mechanisms governing EV biology. Here, we tested whether PDZ proteins, molecular scaffolds that support the formation, transport, and function of signal transduction complexes and that coevolved with multicellularity, may represent important EV regulators. We reveal that the PDZ proteome (ca. 150 proteins in human) establishes a discrete number of direct interactions with the tetraspanins CD9, CD63, and CD81, well-known EV constituents. Strikingly, PDZ proteins interact more extensively with syndecans (SDCs), ubiquitous membrane proteins for which we previously demonstrated an important role in EV biogenesis, loading, and turnover. Nine PDZ proteins were tested in loss-of-function studies. We document that these PDZ proteins regulate both tetraspanins and SDCs, differentially affecting their steady-state levels, subcellular localizations, metabolism, endosomal budding, and accumulations in EVs. Importantly, we also show that PDZ proteins control the levels of heparan sulfate at the cell surface that functions in EV capture. In conclusion, our study establishes that the extensive networking of SDCs, tetraspanins, and PDZ proteins contributes to EV heterogeneity and turnover, highlighting an important piece of the molecular framework governing intracellular trafficking and intercellular communication.

Functional enzyme-polymer complexes.

SignificanceThe use of biological enzyme catalysts could have huge ramifications for chemical industries. However, these enzymes are often inactive in nonbiological conditions, such as high temperatures, present in industrial settings. Here, we show that the enzyme PETase (polyethylene terephthalate [PET]), with potential application in plastic recycling, is stabilized at elevated temperature through complexation with random copolymers. We demonstrate this through simulations and experiments on different types of substrates. Our simulations also provide strategies for designing more enzymatically active complexes by altering polymer composition and enzyme charge distribution.

Proteomimetic Polymers Trigger Potent Antigen-Specific T Cell Responses to Limit Tumor Growth.

Elicitation of effective antitumor immunity following cancer vaccination requires the selective activation of distinct effector cell populations and pathways. Here we report a therapeutic approach for generating potent T cell responses using a modular vaccination platform technology capable of inducing directed immune activation, termed the Protein-like Polymer (PLP). PLPs demonstrate increased proteolytic resistance, high uptake by antigen-presenting cells (APCs), and enhanced payload-specific T cell responses. Key design parameters, namely payload linkage chemistry, degree of polymerization, and side chain composition, were varied to optimize vaccine formulations. Linking antigens to the polymer backbone using an intracellularly cleaved disulfide bond copolymerized with a diluent amount of oligo(ethylene glycol) (OEG) resulted in the highest payload-specific potentiation of antigen immunogenicity, enhancing dendritic cell (DC) activation and antigen-specific T cell responses. Vaccination with PLPs carrying either gp100, E7, or adpgk peptides significantly increased the survival of mice inoculated with B16F10, TC-1, or MC38 tumors, respectively, without the need for adjuvants. B16F10-bearing mice immunized with gp100-carrying PLPs showed increased antitumor CD8+ T cell immunity, suppressed tumor growth, and treatment synergy when paired with two distinct stimulator of interferon gene (STING) agonists. In a human papillomavirus-associated TC-1 model, combination therapy with PLP and 2'3'-cGAMP resulted in 40% of mice completely eliminating implanted tumors while also displaying curative protection from rechallenge, consistent with conferment of lasting immunological memory. Finally, PLPs can be stored long-term in a lyophilized state and are highly tunable, underscoring the unique properties of the platform for use as generalizable cancer vaccines.

Transformations in crystals of DNA-functionalized nanoparticles by electrolytes.

Colloidal crystals have applications in water treatments, including water purification and desalination technologies. It is, therefore, important to understand the interactions between colloids as a function of electrolyte concentration. We study the assembly of DNA-grafted gold nanoparticles immersed in concentrated electrolyte solutions. Increasing the concentration of divalent Ca2+ ions leads to the condensation of nanoparticles into face-centered-cubic (FCC) crystals at low electrolyte concentrations. As the electrolyte concentration increases, the system undergoes a phase change to body-centered-cubic (BCC) crystals. This phase change occurs as the interparticle distance decreases. Molecular dynamics analysis suggests that the interparticle interactions change from strongly repulsive to short-range attractive as the divalent-electrolyte concentration increases. A thermodynamic analysis suggests that increasing the salt concentration leads to significant dehydration of the nanoparticle environment. We conjecture that the intercolloid attractive interactions and dehydrated states favour the BCC structure. Our results gain insight into salting out of colloids such as proteins as the concentration of salt increases in the solution.

Restructuring a passive colloidal suspension using a rotationally driven particle.

The interaction between passive and active/driven particles has introduced a new way to control colloidal suspension properties from particle aggregation to crystallization. Here, we focus on the hydrodynamic interaction between a single rotational driven particle and a suspension of passive particles near the floor. Using experiments and Stokesian dynamics simulations that account for near-field lubrication, we demonstrate that the flow induced by the driven particle can induce long-ranged rearrangement in a passive suspension. We observe an accumulation of passive particles in front of the driven particle and a depletion of passive particles behind the driven particle. This restructuring generates a pattern that can span a range more than 10 times the driven particles radius. We further show that size scale of the pattern is only a function of the particles height above the floor.

Microscopically segregated ligand distribution in co-assembled peptide-amphiphile nanofibers.

Peptide amphiphiles (PAs) self-assemble into cylindrical nanofibers with applications in protein purification, tissue engineering, and regenerative medicine. For these applications, functionalized PAs are often co-assembled with oppositely charged filler PAs. Finding the conditions at which these fibers are homogeneously mixed or segregated is crucial for the required application. We co-assemble negative C12VVEE fillers and positive C12VVKK-OEG4-Z33 ligands, which are important for antibody purifications. Our results show that the ligands tend to cluster and locally segregate in the fiber surfaces. The Z33s are overall neutral and form large aggregates in bulk solution due to short range attractions. However, full segregation of the C12VVKK-OEG4-Z33 is not observed in the cylindrical surface due to the electrostatic penalty of forming large domains of similarly charged molecules. This is commensurate with previous theoretical predictions, showing that the competition between short-range attractive interactions and long-range electrostatic repulsions leads to pattern formation in cylindrical surfaces. This work offers valuable insight into the design of functionalized nanofibers for various biomedical and chemical applications.

Electric fields near undulating dielectric membranes.

Dielectric interfaces are crucial to the behavior of charged membranes, from graphene to synthetic and biological lipid bilayers. Understanding electrolyte behavior near these interfaces remains a challenge, especially in the case of rough dielectric surfaces. A lack of analytical solutions consigns this problem to numerical treatments. We report an analytic method for determining electrostatic potentials near curved dielectric membranes in a two-dimensional periodic "slab" geometry using a periodic summation of Green's functions. This method is amenable to simulating arbitrary groups of charges near surfaces with two-dimensional deformations. We concentrate on one-dimensional undulations. We show that increasing membrane undulation increases the asymmetry of interfacial charge distributions due to preferential ionic repulsion from troughs. In the limit of thick membranes, we recover results mimicking those for electrolytes near a single interface. Our work demonstrates that rough surfaces generate charge patterns in electrolytes of charged molecules or mixed-valence ions.

Chemically controlled pattern formation in self-oscillating elastic shells.

Patterns and morphology develop in living systems such as embryos in response to chemical signals. To understand and exploit the interplay of chemical reactions with mechanical transformations, chemomechanical polymer systems have been synthesized by attaching chemicals into hydrogels. In this work, we design autonomous responsive elastic shells that undergo morphological changes induced by chemical reactions. We couple the local mechanical response of the gel with the chemical processes on the shell. This causes swelling and deswelling of the gel, generating diverse morphological changes, including periodic oscillations. We further introduce a mechanical instability and observe buckling-unbuckling dynamics with a response time delay. Moreover, we investigate the mechanical feedback on the chemical reaction and demonstrate the dynamic patterns triggered by an initial deformation. We show the chemical characteristics that account for the shell morphology and discuss the future designs for autonomous responsive materials.

Outcomes and Associated Extracardiac Malformations in Neonates from Colombia with Severe Congenital Heart Disease.

Congenital heart disease (CHD) is a common structural anomaly, affecting ~ 1% of live births worldwide. Advancements in medical and surgical management have significantly improved survival for children with CHD, however, extracardiac malformations (ECM) continue to be a significant cause of morbidity and mortality. Despite clinical significance, there is limited literature available on ECM in neonates with CHD, especially from Latin America. A cross-sectional study of neonates with severe CHD evaluated by the medical-surgical board team at Fundación Cardiovascular de Colombia from 2014 to 2019 was completed to characterize morbidity, mortality, surgical outcomes, and ECM. Demographics and surgical outcomes were compared between neonates with and without ECM. Medical record data were abstracted and descriptive statistical analysis was performed. Of 378 neonates with CHD, 262 had isolated CHD (69.3%) and 116 had ECM (30.7%). The most common ECM was gastrointestinal (n = 18, 15.5%) followed by central nervous system (n = 14, 12%). Most neonates required a biventricular surgical approach (n = 220, 58.2%). Genetic testing was performed more often for neonates with ECM (n = 65, 56%) than neonates with isolated CHD (n = 14, 5.3%). Neonates with ECM had lower birth weight, longer hospital stays, and higher postsurgical complications rates. There was no difference in survival between groups. Overall, Screening for ECM in neonates with CHD is important and identification of ECM can guide clinical decision-making. These findings have important implications for pediatric healthcare providers, especially in low- and middle-income countries, where the burden of CHD is high and resources for managing CHD and extracardiac malformations may be limited.

Tailoring Interactions of Random Copolymer Polyelectrolyte Complexes to Remove Nanoplastic Contaminants from Water.

We investigate the usage of polyelectrolyte complex materials for water remediation purposes, specifically their ability to remove nanoplastics from water, on which there is currently little to no prior research. We demonstrate that oppositely charged random copolymers are effective at quantitatively removing nanoplastic contamination from aqueous solution. The mechanisms underlying this remediation ability are explored through computational simulations, with corroborating quartz crystal microbalance adsorption experiments. We find that hydrophobic nanostructures and interactions likely play an important role.

Surface polarization enhances ionic transport and correlations in electrolyte solutions nanoconfined by conductors.

Layered materials that perform mixed electron and ion transport are promising for energy harvesting, water desalination, and bioinspired functionalities. These functionalities depend on the interaction between ionic and electronic charges on the surface of materials. Here we investigate ion transport by an external electric field in an electrolyte solution confined in slit-like channels formed by two surfaces separated by distances that fit only a few water layers. We study different electrolyte solutions containing monovalent, divalent, and trivalent cations, and we consider walls made of non-polarizable surfaces and conductors. We show that considering the surface polarization of the confining surfaces can result in a significant increase in ionic conduction. The ionic conductivity is increased because the conductors' screening of electrostatic interactions enhances ionic correlations, leading to faster collective transport within the slit. While important, the change in water's dielectric constant in confinement is not enough to explain the enhancement of ion transport in polarizable slit-like channels.

Positional ordering induced by dynamic steric interactions in superparamagnetic rods.

The dynamic motion produced by precessing magnetic fields can drive matter into far-from-equilibrium states. We predict 1D periodic ordering in systems of precessing rods when magnetic interactions between rods remain insignificant. The precession angle of the rods is completely determined by the field's precession angle and the ratio of the field's precession frequency and the characteristic response frequency of the rods. We develop a molecular dynamics model that explicitly calculates magnetic interactions between particles, and we also simulate rods in the limit of a strong and fast precessing magnetic field where inter-rod magnetic interactions are negligible, using a purely steric model. Our simulations show how steric interactions drive the rods from a positionally disordered phase (nematic) to a layered (smectic) phase. As the rod precession angle increases, the nematic-smectic transition density significantly decreases. The minimization of unfavorable steric interactions also induces phase separation in binary mixtures of rods of different lengths. This effect is general to any force that produces precession in elongated particles. This work will advance the understanding and control of out-of-equilibrium soft matter systems.

Janus magnetoelastic membrane swimmers.

Soft swimming microrobots have attracted considerable attention due to their potential applications in diverse fields ranging from biomedicines to environmental remediation. The locomotion control is of importance to the research of micromachines and microrobots. Inspired by the motility strategies of living microorganisms, such as flagella, cilia, and euglenoids, we focus on propulsion mechanisms with a design of Janus magnetoelastic crystalline membrane microswimmers actuated by time-varying magnetic fields. Such a Janus swimmer consists of a ferromagnetic cap completed by a magnetoelastic membrane body, where superparamagnetic particles are uniformly distributed on the surface. Under the influence of external magnetic fields, the swimmer undergoes complex shape transitions due to the interplay between the magnetic dipole-dipole interactions, the elasticity of the magnetoelastic membranes, and also the hydrodynamics of surrounding fluids. We show that those shape changes are nonreciprocal, which can generate locomotion such that the propulsion speed can be optimized by tailoring the membrane elastic properties. Besides, we also demonstrate that the Janus swimmer can be magnetically guided in a spiral trajectory. With such adequate control of locomotion in both speed and direction via non-invasive magnetic fields, this study provides another promising candidate design for the future development of microswimmers.

Induced phase transformation in ionizable colloidal nanoparticles.

Acid-base equilibria directly influence the functionality and behavior of particles in a system. Due to the ionizing effects of acid-base functional groups, particles will undergo charge exchange. The degree of ionization and their intermolecular and electrostatic interactions are controlled by varying the pH and salt concentration of the solution in a system. Although the pH can be tuned in experiments, it is hard to model this effect using simulations or theoretical approaches. This is due to the difficulty in treating charge regulation and capturing the cooperative effects in a colloidal suspension with Coulombic interaction. In this work, we analyze a suspension of ionizable colloidal particles via molecular dynamics (MD) simulations, along with Monte Carlo simulations for charge regulation (MC-CR) and derive a phase diagram of the system as a function of pH. It is observed that as pH increases, particles functionalized with acid groups change their arrangement from face-centered cubic (FCC) packing to a disordered state. We attribute these transitions to an increase in the degree of charge polydispersity arising from an increase in pH. Our work shows that charge regulation leads to amorphous solids in colloids when the mean nanoparticle charge is sufficiently high.

Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients.

BACKGROUND: The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients. METHODS: Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT). RESULTS: 184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation. CONCLUSIONS: A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.