Probing and Manipulating Noncovalent Interactions in Functional Polymeric Systems.

Noncovalent interactions, which usually feature tunable strength, reversibility, and environmental adaptability, have been recognized as driving forces in a variety of biological and chemical processes, contributing to the recognition between molecules, the formation of molecule clusters, and the establishment of complex structures of macromolecules. The marriage of noncovalent interactions and conventional covalent polymers offers the systems novel mechanical, physicochemical, and biological properties, which are highly dependent on the binding mechanisms of the noncovalent interactions that can be illuminated via quantification. This review systematically discusses the nanomechanical characterization of typical noncovalent interactions in polymeric systems, mainly through direct force measurements at microscopic, nanoscopic, and molecular levels, which provide quantitative information (e.g., ranges, strengths, and dynamics) on the binding behaviors. The fundamental understandings of intermolecular and interfacial interactions are then correlated to the macroscopic performances of a series of noncovalently bonded polymers, whose functions (e.g., stimuli-responsiveness, self-healing capacity, universal adhesiveness) can be customized through the manipulation of the noncovalent interactions, providing insights into the rational design of advanced materials with applications in biomedical, energy, environmental, and other engineering fields.

Principles of Cation-π Interactions for Engineering Mussel-Inspired Functional Materials.

Supramolecular assembly is commonly driven by noncovalent interactions (e.g., hydrogen bonding, electrostatic, hydrophobic, and aromatic interactions) and plays a predominant role in multidisciplinary research areas ranging from materials design to molecular biology. Understanding these noncovalent interactions at the molecular level is important for studying and designing supramolecular assemblies in chemical and biological systems. Cation-π interactions, initially found through their influence on protein structure, are generally formed between electron-rich π systems and cations (mainly alkali, alkaline-earth metals, and ammonium). Cation-π interactions play an essential role in many biological systems and processes, such as potassium channels, nicotinic acetylcholine receptors, biomolecular recognition and assembly, and the stabilization and function of biomacromolecular structures. Early fundamental studies on cation-π interactions primarily focused on computational calculations, protein crystal structures, and gas- and solid-phase experiments. With the more recent development of spectroscopic and nanomechanical techniques, cation-π interactions can be characterized directly in aqueous media, offering opportunities for the rational manipulation and incorporation of cation-π interactions into the design of supramolecular assemblies. In 2012, we reported the essential role of cation-π interactions in the strong underwater adhesion of Asian green mussel foot proteins deficient in l-3,4-dihydroxyphenylalanine (DOPA) via direct molecular force measurements. In another study in 2013, we reported the experimental quantification and nanomechanics of cation-π interactions of various cations and π electron systems in aqueous solutions using a surface forces apparatus (SFA).Over the past decade, much progress has been achieved in probing cation-π interactions in aqueous solutions, their impact on the underwater adhesion and cohesion of different soft materials, and the fabrication of functional materials driven by cation-π interactions, including surface coatings, complex coacervates, and hydrogels. These studies have demonstrated cation-π interactions as an important driving force for engineering functional materials. Nevertheless, compared to other noncovalent interactions, cation-π interactions are relatively less investigated and underappreciated in governing the structure and function of supramolecular assemblies. Therefore, it is imperative to provide a detailed overview of recent advances in understanding of cation-π interactions for supramolecular assembly, and how these interactions can be used to direct supramolecular assembly for various applications (e.g., underwater adhesion). In this Account, we present very recent advances in probing and applying cation-π interactions for mussel-inspired supramolecular assemblies as well as their structural and functional characteristics. Particular attention is paid to experimental characterization techniques for quantifying cation-π interactions in aqueous solutions. Moreover, the parameters responsible for modulating the strengths of cation-π interactions are discussed. This Account provides useful insights into the design and engineering of smart materials based on cation-π interactions.

Mussel-Inspired Cation-π Interactions: Wet Adhesion and Biomimetic Materials.

Cation-π interaction is one of the most important noncovalent interactions identified in biosystems, which has been proven to play an essential role in the strong adhesion of marine mussels. In addition to the well-known catecholic amino acid, l-3,4-dihydroxyphenylalanine, mussel foot proteins are rich in various aromatic moieties (e.g., tyrosine, phenylalanine, and tryptophan) and cationic residues (e.g., lysine, arginine, and histidine), which favor a series of short-range cation-π interactions with adjustable strengths, serving as a prototype for the development of high-performance underwater adhesives. This work highlights our recent advances in understanding and utilizing cation-π interactions in underwater adhesives, focusing on three aspects: (1) the investigation of the cation-π interaction mechanisms in mussel foot proteins via force-measuring techniques; (2) the modulation of cation-π interactions in mussel mimetic polymers with the variation of cations, anions, and aromatic groups; (3) the design of wet adhesives based on these revealed principles, leading to functional materials in the form of films, coacervates, and hydrogels with biomedical and engineering applications. This review provides valuable insights into the development and optimization of smart materials based on cation-π interactions.

Probing Hydrophobic Interactions between Polymer Surfaces and Air Bubbles or Oil Droplets: Effects of Molecular Weight and Surfactants.

Hydrophobic interaction plays an important role in numerous interfacial phenomena and biophysical and industrial processes. In this work, polystyrene (PS) was used as a model hydrophobic polymer for investigating its hydrophobic interaction with highly deformable objects (i.e., air bubbles and oil droplets) in aqueous solutions. The effects of polymer molecular weight, solvent (i.e., addition of ethanol to water), the presence of surface-active species, and hydrodynamic conditions were investigated, via direct surface force measurements using the bubble/drop probe atomic force microscopy (AFM) technique and theoretical calculations based on the Reynolds lubrication theory and augmented Young-Laplace equation by including the effect of disjoining pressure. It was found that the PS of low molecular weight (i.e., PS590 and PS810) showed slightly weaker hydrophobic interactions with air bubbles or oil droplets, as compared to glassy PS of higher molecular weight (i.e., PS1110, PS2330, PS46300, and PS1M). The hydrophobic interaction between PS and air bubbles in a 1 M NaCl aqueous solution with 10 vol % ethanol was weaker than that in the bare aqueous solution. Such effects on the hydrophobic interactions are possibly achieved by influencing the structuring/ordering of water molecules close to the hydrophobic polymer surfaces by tuning the surface chain mobility and surface roughness of polymers. It was found that the addition of three surface-active species, i.e., cetyltrimethylammonium chloride (CTAC), Pluronic F-127, and sodium dodecyl sulfate (SDS), to the aqueous media could suppress the attachment of the hydrophobic polymer and air bubbles or oil droplets, most likely caused by the additional steric repulsion due to the adsorbed surface-active species at the bubble/polymer/oil interfaces. Our results have improved the fundamental understanding of the interaction mechanisms between hydrophobic polymers and gas bubbles or oil droplets, with useful implications on developing effective methods for modulating the related interfacial interactions in many engineering applications.

Adhesive Coacervates Driven by Hydrogen-Bonding Interaction.

Coacervation plays a critical role in numerous biological activities such as constructing biological tissues and achieving robust wet adhesion of marine sessile organisms, which conventionally occurs when oppositely charged polyelectrolytes are mixed in aqueous solutions driven by electrostatic attraction. Here, a novel type of adhesive coacervate is reported, driven by hydrogen-bonding interactions, readily formed by mixing silicotungstic acid and nonionic polyethylene glycol in water, providing a new approach for developing coacervates from nonionic systems. The as-prepared coacervate is easily paintable underwater, show strong wet adhesion to diverse substrates, and has been successfully applied as a hemostatic agent to treat organ injuries without displaying hemolytic activity, while with inherent antimicrobial properties thus avoiding inflammations and infections due to microorganism accumulation. This work demonstrates that coacervation can occur in salt-free environments via non-electrostatic interactions, providing a new platform for engineering multifunctional coacervate materials as tissue glues, wound dressings and membrane-free cell systems.

Injectable and Self-Healing Nanocomposite Hydrogels with Ultrasensitive pH-Responsiveness and Tunable Mechanical Properties: Implications for Controlled Drug Delivery.

Injectable, self-healing, and pH-responsive hydrogels are great intelligent drug delivery systems for controlled and localized therapeutic release. Hydrogels that show pH-sensitive behaviors in the mildly acidic range are ideal to be used for the treatment of regions showing local acidosis like tumors, wounds and infections. In this work, we present a facile preparation of an injectable, self-healing, and supersensitive pH-responsive nanocomposite hydrogel based on Schiff base reactions between aldehyde-functionalized polymers and amine-modified silica nanoparticles. The hydrogel shows fast gelation within 10 s, injectability, and rapid self-healing capability. Moreover, the hydrogel demonstrates excellent stability under neutral physiological conditions, while a sharp gel-sol transition is observed, induced by a faintly acidic environment, which is desirable for controlled drug delivery. The pH-responsiveness of the hydrogel is ultrasensitive, where the mechanical properties, hydrolytic degradation, and drug release behaviors can alter significantly when subjected to a slight pH change of 0.2. Additionally, the hydrogel's mechanical and pH-responsive properties can be readily tuned by its composition. Its excellent biocompatibility is confirmed by cytotoxicity tests toward human dermal fibroblast cells (HDFa). The novel injectable, self-healing, and sensitive pH-responsive hydrogel serves as a promising candidate as a localized drug carrier with controlled delivery capability, triggered by acidosis, holding great promise for cancer therapy, wound healing, and infection treatment.

Syndrome of inappropriate anti-diuretic hormone secretion secondary to disseminated strongyloidiasis in a kidney transplant recipient: A case report.

Background: Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) is associated with strongyloidiasis. Herein, a rare case of severe SIADH secondary to disseminated strongyloidiasis in a kidney transplant recipient is reported. Case presentation: A case involving a 43-year-old male kidney transplant recipient with severe disseminated Strongyloides stercoralis infection is reported. The patient was a construction worker with a history of consuming undercooked yellow eel and sashimi. On admission, the patient presented with poor appetite, nausea, vomiting and diarrhea. Laboratory investigations revealed persistent significant hyponatremia and low serum osmolality, confirming the diagnosis of SIADH. S. stercoralis was detected in the stool and bronchoalveolar lavage fluid. He was treated with empirical albendazole because S. stercoralis was detected in the stool; however, his symptoms and hyponatremia did not improve until ivermectin was administered, after which SIADH resolved quickly. Conclusion: This case suggests that S. stercoralis infection should be included in the differential diagnosis when a kidney transplant recipient presents with gastrointestinal symptoms and SIADH. In such situations, pre- or post-transplant screening for S. stercoralis is needed, and early ivermectin treatment is very important.

Surface interaction mechanisms of air bubbles, asphaltenes and oil drops in aqueous solutions with implications for interfacial engineering processes.

HYPOTHESIS: Surface interactions of bubbles and oil with interface-active species like asphaltenes influence many interfacial phenomena in various engineering processes. It holds both fundamental and practical significance to quantitatively characterize these interactions. EXPERIMENTS: The surface forces of air bubbles, asphaltenes and asphaltenes-toluene droplets in various aqueous solutions have been quantified using an integrated thin film drainage apparatus and an atomic force microscope coupled with bubble probe. The effects of asphaltenes concentration, pH, salinity, Ca2+ ions and surfactants have been examined. FINDINGS: Hydrophobic interaction drives attachment of bubbles and asphaltenes surfaces or oil droplets under high salinity condition. Increasing asphaltenes concentration in oil droplets enhances their hydrophobic attraction with bubbles due to strengthened asphaltenes adsorption and aggregation at oil-water interface. Increasing pH weakens the hydrophobic interaction as oil surfaces become more negatively charged and less hydrophobic. Under low salinity condition, strong electrical double layer and van der Waals repulsion inhibits the bubble-oil droplet contact. Introducing Ca2+ ions and surfactants leads to strong steric repulsion, preventing bubble-oil contact. This research has advanced our mechanistic understanding of how bubbles and oil droplets interact in aqueous systems and offers useful insights to modulate such interactions in oil production, water treatment and other interfacial processes.

A pH and Temperature Dual-Responsive Microgel-Embedded, Adhesive, and Tough Hydrogel for Drug Delivery and Wound Healing.

Stimuli-responsive hydrogels have attracted much attention over the past decade for potential bioengineering applications such as wound dressing and drug delivery. In this work, a pH and temperature dual-responsive microgel-embedded hydrogel has been fabricated by incorporating poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAAm-co-AAc) based microgel particles into polyacrylamide (PAAm)/chitosan (CS) semi-interpenetrating polymer network (semi-IPN), denoted as microgel@PAM/CS. The resultant hydrogel possesses excellent mechanical properties including stretchability, compressibility, and elasticity. In addition, the microgel@PAM/CS hydrogels can tightly adhere to the surfaces of a variety of tissues such as porcine skin, kidney, intestine, liver, and heart. Moreover, it shows controlled dual-drug release profile of both bovine serum albumin (BSA) (as a model protein) and sulfamethoxazole (SMZ), an antibiotic. Excellent antimicrobial properties are obtained for SMZ-loaded microgel@PAM/CS hydrogels. Compared with traditional drug administration methods such as by mouth, injection, and inhalation, the microgel@PAM/CS hydrogels possess advantages such as higher drug loading efficiency (by more than 80%) and controllable and sustained (over 48 h) release. The microgel@PAM/CS hydrogels can significantly enhance the wound healing process. This work provides a facile approach for the fabrication of multifunctional stimuli-responsive microparticle-embedded hydrogels with semi-IPN structures, and the as-prepared microgel@PAM/CS hydrogels have great potential for applications as smart wound dressing materials in biomedical engineering.

Stretchable, compressible, and conductive hydrogel for sensitive wearable soft sensors.

Conductive hydrogels hold great promises in wearable soft electronics. However, the weak mechanical properties, low sensitivity and the absence of multifunctionalities (e.g., self-healing, self-adhesive, etc.) of the conventional conductive hydrogels limit their applications. Thus, developing multifunctional hydrogels may address some of these technical issues. In this work, a multifunctional conductive hydrogel strain sensor is fabricated by incorporating a conductive polymer Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS) into a mechanically robust poly (vinyl alcohol) (PVA)/ poly (acrylic acid) (PAA) double network (DN) hydrogel. The as-prepared hydrogel sensor could span a wide spectrum of mechanical properties by simply tuning the polymer composition and the number of freezing-thawing cycles. In addition, the dynamic hydrogen bonding interactions endow the hydrogel sensor with self-healing property and reversible adhesiveness on diverse substrates. Moreover, the hydrogel sensor shows high sensitivity (Gauge Factor from 2.21 to 3.82) and can precisely detect some subtle human motions (e.g., pulse and vocal cord vibration). This work provides useful insights into the development of conductive hydrogel-based wearable soft electronics.

Coacervate-Based Instant and Repeatable Underwater Adhesive with Anticancer and Antibacterial Properties.

Underwater adhesion is a great challenge for the development of adhesives as the attractive interfacial intermolecular interactions are usually weakened by the surface hydration layer. The coacervation process of sessile organisms like marine mussels and sandcastle worms has inspired substantial research interest in the fabrication of long-lasting underwater adhesives, but they generally suffer from time-consuming curing triggered by surrounding environmental changes and cannot reserve the adhesiveness once damaged. Herein, an instant and repeatable underwater adhesive was developed based on the coacervation of tannic acid (TA) and poly(ethylene glycol)77-b-poly(propylene glycol)29-b-poly(ethylene glycol)77 (PEG-PPG-PEG, F68), which was driven by hydrogen-bonding interaction, and the hydrophobic cores of F68 micelles offered an additional cross-linking to enhance the mechanical properties. The TA-F68 coacervates could be facilely painted on different substrates, exhibiting robust and instant underwater adhesion (with adhesion strength up to 1.1 MPa on porcine skin) and excellent repeatability (at least 1000 cycles), superior to the previously reported coacervates. Due to the biological activities of TA, the underwater adhesive displayed innate anticancer and antibacterial properties against different types of cancer cells and bacteria, showing great potential for diverse biomedical applications, such as injectable drug carriers, tissue glues, and wound dressings.

Surface interaction mechanisms in mineral flotation: Fundamentals, measurements, and perspectives.

As non-renewable natural resources, minerals are essential in a broad range of biological and technological applications. The surface interactions of mineral particles with other objects (e.g., solids, bubbles, reagents) in aqueous suspensions play a critical role in mediating many interfacial phenomena involved in mineral flotation. In this work, we have reviewed the fundamentals of surface forces and quantitative surface property-force relationship of minerals, and the advances in the quantitative measurements of interaction forces of mineral-mineral, bubble-mineral and mineral-reagent using nanomechanical tools such as surface forces apparatus (SFA) and atomic force microscope (AFM). The quantitative correlation between surface properties of minerals at the solid/water interface and their surface interaction mechanisms with other objects in complex aqueous media at the nanoscale has been established. The existing challenges in mineral flotation such as characterization of anisotropic crystal plane or heterogeneous surface, low recovery of fine particle flotation, and in-situ electrochemical characterization of collectorless flotation as well as the future work to resolve the challenges based on the understanding and modulation of surface forces of minerals have also been discussed. This review provides useful insights into the fundamental understanding of the intermolecular and surface interaction mechanisms involved in mineral processing, with implications for precisely modulating related interfacial interactions towards the development of highly efficient industrial processes and chemical additives.