Amphiphilic Structure Research Articles

Electrohydrodynamic Techniques for the Manufacture and/or Immobilization of Vesicles.

The development of accurate drug delivery systems is one of the main challenges in the biomedical field. A huge variety of structures, such as vesicles, nanoparticles, and nanofibers, have been proposed as carriers for bioactive agents, aiming for precision in administration and dosage, safety, and bioavailability. This review covers the use of electrohydrodynamic techniques both for the immobilization and for the synthesis of vesicles in a non-conventional way. The state of the art discusses the most recent advances in this field as well as the advantages and limitations of electrospun and electrosprayed amphiphilic structures as precursor templates for the in situ vesicle self-assembly. Finally, the perspectives and challenges of combined strategies for the development of advanced structures for the delivery of bioactive agents are analyzed.

The Synthesis and Transfection Activity of Disulfide Polycationic Amphiphiles.

Some new polycationic amphiphiles containing a disulfide group were synthesized. Cationic liposomes formed from the compounds synthesized and a helper lipid 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine were not toxic for HEK293 and HeLa cells and were highly effective when delivering a fluorescently labeled oligodeoxyribonucleotide. The efficacy of plasmid DNA delivery depended on the cell line and the amphiphile structure, liposomes based on tetracationic amphiphiles being the most effective transfectants. These liposomes can be used for in vitro transfection of eukaryotic cells as well as for further in vivo biological studies.

Quantification of biophysical properties of candidalysin, a fungal peptide toxin secreted by C. albicans during invasion.

Candida albicans fungus can cause invasive candidiasis. To become pathogenic and translocate across the intestinal epithelium C.abicans fungus needs to change its morphology from yeast to invasive filamentous. Virulence factor candidalysin secreted during fungal invasion, is found to be crucial in direct cell membrane damage, the stimulation of a danger response signalling pathway, and the activation of epithelial immunity. Due to its amphiphilic alpha-helical structure peptide has a high binding affinity to plasma membranes. With increasing accumulation on the membrane surfaces, the alpha-helix peptide starts penetration of the lipid bilayer until the plasma membrane is damaged. However, whether there is specific affinity to different membrane compositions is still unknown. Here we determined the concentrations of candidalysin required for membrane permeabilization of large unilamellar vesicles with various lipid compositions. Then, we used spectral imaging to assess the lipid packing changes in giant unilamellar vesicles of different lipid composition resembling human epithelial, bacterial and fungal membranes under the treatment of candidalysin. Solvatochromic polarity-sensitive dyes were used to label model membranes. Spectral imaging data allowed to calculate generalized polarization map of the labelled membrane and further investigate lipid packing during peptide binding.

Amber Light Control of Peptide Secondary Structure by a Perfluoroaromatic Azobenzene Photoswitch.

The incorporation of photoswitches into the molecular structure of peptides and proteins enables their dynamic photocontrol in complex biological systems. Here, a perfluorinated azobenzene derivative triggered by amber light was site-specifically conjugated to cysteines in a helical peptide by perfluoroarylation chemistry. In response to the photoisomerization (trans→cis) of the conjugated azobenzene with amber light, the secondary structure of the peptide was modulated from a disorganized into an amphiphilic helical structure.

Peptide-Protein Coassemblies into Hierarchical and Bioactive Tubular Membranes.

Multicomponent self-assembly offers opportunities for the design of complex and functional biomaterials with tunable properties. Here, we demonstrate how minor modifications in the molecular structures of peptide amphiphiles (PAs) and elastin-like recombinamers (ELs) can be used to generate coassembling tubular membranes with distinct structures, properties, and bioactivity. First, by introducing minor modifications in the charge density of PA molecules (PAK2, PAK3, PAK4), different diffusion-reaction processes can be triggered, resulting in distinct membrane microstructures. Second, by combining different types of these PAs prior to their coassembly with ELs, further modifications can be achieved, tuning the structures and properties of the tubular membranes. Finally, by introducing the cell adhesive peptide RGDS in either the PA or EL molecules, it is possible to harness the different diffusion-reaction processes to generate tubular membranes with distinct bioactivities. The study demonstrates the possibility to trigger and achieve minor but crucial differences in coassembling processes and tune material structure and bioactivity. The study demonstrates the possibility to use minor, yet crucial, differences in coassembling processes to tune material structure and bioactivity.

Adenosine Triphosphate-Responsive Glyconanorods through Self-Assembly of β-Cyclodextrin-Based Glycoconjugates for Targeted and Effective Bacterial Sensing and Killing.

Polymer-based nanomaterials have exhibited promising alternative avenues to combat the globe challenge of multidrug-resistant bacterial infection. However, most of the reported polymeric nanomaterials have facially linear amphiphilic structures with positive net charges, which may lead to nonspecific binding, high hemolysis, and uncontrollable self-organization, limiting their practical applications. In this contribution, we report a one-dimensional glyconanorod (GNR) through self-assembly of well-defined β-cyclodextrin-based glycoconjugates (RMan) featuring hydrophobic carbon-based chains and amide rhodamines with an adenosine triphosphate (ATP)-recognition site and targeted and hydrophilic mannoses and positively net-charged ethylene amine groups. The GNRs show superior targeting sensing and killing for Gram-negative Escherichia coli (E. coli) dominantly through the multivalent recognition between mannoses on the nanorod and the lectin on the surface of E. coli. Moreover, red fluorescence was light on due to the hydrogen bonding between amide rhodamine and ATP. Benefiting from the designs, the GNRs are capable of possessing a higher therapeutic index and of encapsulating other antibiotics. They exhibit an enhanced effect against E. coli strains. Intriguingly, the GNRs displayed a more reduced hemolysis effect and lower cytotoxicity compared to that of ethylene glyco-modified nanorods. These results reveal that the glyconanomaterials not only feature superior and targeted bacterial sensing and antibacterial activity, but also better biocompatibility compared with the widely used PEG-covered nanomaterials. Furthermore, the in vivo studies demonstrate that the targeted and ATP-responsive GNRs complexed with antibiotics showed better treatment using a mouse model of abdominal sepsis following intraperitoneal E. coli infection. The present work describes a targeted and effective sensing and antibacterial platform based on glycoconjugates that have potential applications for the treatment of infections caused by pathogenic microorganisms.

Single-Component Physical Hydrogels of Dendritic Molecules

Hydrogels are hydrophilic, three-dimensional networks able to imprison large amounts of water and are largely used in pharmaceutical formulations. Hydrogels are frequently obtained from hydrophilic polymers, either natural, biohybrid, or synthetic. Owing to their peculiar structure, dendrimers can be considered prospective building blocks for hydrogel networks. This review gathers the use of different types of amphiphilic dendritic structures able to generate physical hydrogels alone. Such dendritic structures comprise dendrimers, Janus dendrimers, and dendrons. The first part concerns different types of positively charged phosphorus dendrimers used to generate hydrogels, which are also suitable to form fibers, and for encapsulating diverse substances, or forming complexes with genetic materials for their slow delivery. The second part concerns PAMAM dendrimers functionalized with collagen mimetics. The third part concerns amphiphilic Janus dendrimers, whereas the fourth part displays different types of amphiphilic dendrons and their use, in particular in the fields of materials and drug delivery.

Bacterial susceptibility and resistance to modelin-5.

Modelin-5 (M5-NH2) killed Pseudomonas aeruginosa with a minimum lethal concentration (MLC) of 5.86 μM and strongly bound its cytoplasmic membrane (CM) with a Kd of 23.5 μM. The peptide adopted high levels of amphiphilic α-helical structure (75.0%) and penetrated the CM hydrophobic core (8.0 mN m-1). This insertion destabilised CM structure via increased lipid packing and decreased fluidity (ΔGmix < 0), which promoted high levels of lysis (84.1%) and P. aeruginosa cell death. M5-NH2 showed a very strong affinity (Kd = 3.5 μM) and very high levels of amphiphilic α-helical structure with cardiolipin membranes (96.0%,) which primarily drove the peptide's membranolytic action against P. aeruginosa. In contrast, M5-NH2 killed Staphylococcus aureus with an MLC of 147.6 μM and weakly bound its CM with a Kd of 117.6 μM, The peptide adopted low levels of amphiphilic α-helical structure (35.0%) and only penetrated the upper regions of the CM (3.3 mN m-1). This insertion stabilised CM structure via decreased lipid packing and increased fluidity (ΔGmix > 0) and promoted only low levels of lysis (24.3%). The insertion and lysis of the S. aureus CM by M5-NH2 showed a strong negative correlation with its lysyl phosphatidylglycerol (Lys-PG) content (R2 > 0.98). In combination, these data suggested that Lys-PG mediated mechanisms inhibited the membranolytic action of M5-NH2 against S. aureus, thereby rendering the organism resistant to the peptide. These results are discussed in relation to structure/function relationships of M5-NH2 and CM lipids that underpin bacterial susceptibility and resistance to the peptide.

Deoxyestrone-based lipofection agents with solution- and solid-state emission properties.

In this contribution, three deoxyestrone-based emissive lipofection agents are reported. Because of a centrally incorporated terephthalonitrile motif, these ligands can be classified as solution and solid-state emitters (SSSEs). With the attachment of tobramycin, these amphiphilic structures are able to form lipoplexes, mediating gene transfection of HeLa and HEK 293T cells.

Zwitterionic rhodamine-CPT prodrug nanoparticles with GSH/H2O2 responsiveness for cancer theranostics.

Rationale: Fluorescently traceable prodrugs, which can monitor their biodistribution in vivo and track the kinetics of drug delivery in living cells, are promising for constructing theranostic medicines. However, due to their charge and hydrophobicity, most of the fluorescently traceable prodrugs exhibit high protein binding and non-specific tissue retention affecting in vivo distribution and toxicity, with high background signals. Methods: Herein, the zwitterionic rhodamine (RhB) and camptothecin (CPT) were bridged with a disulfide bond to construct a tumorous heterogeneity-activatable prodrug (RhB-SS-CPT). The interaction of zwitterionic RhB-SS-CPT with proteins was detected by UV and fluorescence spectroscopy, and further demonstrated by molecular docking studies. Then, intracellular tracking and cytotoxicity of RhB-SS-CPT were determined in tumor and normal cells. Finally, the in vivo biodistribution, pharmacokinetics, and anticancer efficacy of RhB-SS-CPT were evaluated in a mouse animal model. Results: The tumorous heterogeneity-activatable RhB-SS-CPT prodrug can self-assemble into stable nanoparticles in water based on its amphiphilic structure. Particularly, the zwitterionic prodrug nanoparticles reduce the non-specific binding to generate a low background signal for better identification of cancerous lesions, achieve rapid internalization into cancer cells, selectively release bioactive CPT as a cytotoxic agent in response to high levels of GSH and H2O2, and exhibit high fluorescence that contributes to the visual chemotherapy modality. In addition, the RhB-SS-CPT prodrug nanoparticles show longer circulation time and better antitumor activity than free CPT in vivo. Interestingly, the zwitterionic nature allows RhB-SS-CPT to be excreted through the renal route, with fewer side effects. Conclusions: Zwitterionic features and responsive linkers are important considerations for constructing potent prodrugs, which provide some useful insights to design the next-generation of theranostic prodrugs for cancer.

Potential of Small‐Angle Neutron Scattering for Evaluating Protein Locus within a Polymersome

Inside Cover: In article 2200300 by Albena Lederer and co-workers, a specific amphiphilic copolymer structure defines the formation of polymersomes, which mimic diffusion processes through biological membranes. The locus of the cargo and the membrane conformation after diffusion are still open questions. Small-angle neutron scattering in combination with multidetecton fractionation opens new opportunities to evaluate membrane alteration after post-loading.

Synthesis of mesoporous zeolite Y using Sapindus rarak extract as natural organic surfactant for deoxygenation of Reutealis trisperma oil to biofuel.

Saponin is a plant-derived chemical with an amphiphilic glycoconjugate structure extracted from sapindaceae plants like Sapindus rarak. This study investigated saponin extract of Sapindus rarak as a natural template for formation of mesoporous zeolite Y. Surface area and mesoporosity of zeolite Y were improved with optimization of Sapindus rarak extract (SRE) concentration (Y-Ln; n = 2, 5, 10 or 15 mL), reaching 216.26 m2 mesoporous area and 0.214 cm3 g-1 mesoporous volume for Y-L10 samples. A different loading of Ni was impregnated onto Y-L10 zeolite to improve Lewis/Brønsted acidity as catalysts in the deoxygenation of Reutealis trisperma oil (RTO) into hydrocarbon fuels. Impregnating 15% Ni on NaY zeolite enhanced Lewis acidity to 0.4556 mmol g-1, producing 48.8% liquid oil with 85.43% degree of deoxygenation. A high selectivity towards C15 and C17 hydrocarbon was analyzed from liquid yield, indicating the contributing factor from Lewis acidity and mesoporosity to enhance deoxygenation and prevent the hydrocracking reaction.

Controlling the structure of supramolecular fibre formation for benzothiazole based hydrogels with antimicrobial activity against methicillin resistant Staphylococcus aureus.

Antimicrobial resistance is one of the greatest threats to human health. Gram-positive methicillin resistant Staphylococcus aureus (MRSA), in both its planktonic and biofilm form, is of particular concern. Herein we identify the hydrogelation properties for a series of intrinsically fluorescent, structurally related supramolecular self-associating amphiphiles and determine their efficacy against both planktonic and biofilm forms of MRSA. To further explore the potential translation of this hydrogel technology for real-world applications, the toxicity of the amphiphiles was determined against the eukaryotic multicellular model organism, Caenorhabditis elegans. Due to the intrinsic fluorescent nature of these supramolecular amphiphiles, material characterisation of their molecular self-associating properties included; comparative optical density plate reader assays, rheometry and widefield fluorescence microscopy. This enabled determination of amphiphile structure and hydrogel sol dependence on resultant fibre formation.

Supramolecular temperature responsive assembly of polydopamine reduced graphene oxide.

Graphene oxide (GO) and reduced graphene oxide (rGO) colloidal systems can directly respond to environmental stimuli such as pH, ionic strength, and light by themselves, but not to temperature. Here we show that surface modification of rGO with polydopamine (PDA) leads to a temperature-responsive composite material, even though neither rGO nor PDA have intrinsic temperature responsiveness. Reducing GO with dopamine results in rGO/PDA flakes with hydrophilic PDA clusters attached to hydrophobic rGO domains, which mimics the amphiphilic structure of temperature responsive poly(N-isopropylacrylamide) (PNIPAM). The rGO/PDA flakes self-assemble at temperature higher than 30 °C, causing flake aggregation and precipitation in suspensions with concentration of 0.05 g L-1, which is reversible upon cooling, shaking, and re-heating. A solution-to-gelation transition occurs upon heating suspensions with concentration of 10 g L-1. Nacre-like films and porous monoliths are obtained by drying rGO/PDA suspensions at different concentrations. Films and porous monoliths obtained by drying suspensions that are previously self-assembled through heat have more compact structures compared to those obtained with suspensions that are not heated. Overall, this work introduces the concept of supramolecular temperature responsive assembly of nanomaterials (STRAN), i.e., that temperature response can be introduced in nanomaterials by combining non-responsive components that function cooperatively in supramolecules, whose interactions with solvents can be modulated by temperature changes, mimicking what happens in macromolecular systems such as PNIPAM. STRAN could be applied to nanomaterials beyond GO to develop responsive systems whose self-assembly in suspension and architectural features realized upon drying can be controlled by temperature.

Noncovalent Bile Acid Oligomers as Facial Amphiphilic Antimicrobials.

New antimicrobial agents are needed to address the ever-growing risk of bacterial resistance, particularly for methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus). Here, we report a class of bile acid oligomers as facial amphiphilic antimicrobials, which are noncovalently fabricated by cholic acid (CA) and deoxycholic acid (DCA) with polyamines (e.g., diamines, diethylenetriamine, spermidine, and spermine). The antibacterial activities of these bile acid oligomers (CA/polyamines and DCA/polyamines) against S. aureus become stronger with increasing the amine group numbers of polyamines without obviously enhanced cytotoxicity and skin irritation. DCA/spermine, entirely composed of natural products, exhibits the best antibacterial activity but the lowest cytotoxicity and the weakest skin irritation. All CA/polyamines and DCA/polyamines form well-ordered ribbon-like aggregates, collecting numerous facial amphiphilic structures to significantly enhance the interactions with bacterial membranes. In particular, the biogenic polyamines with more than two amine groups provide extra positively charged sites, hence facilitating the binding of bile acid oligomers to the negatively charged outer membrane of the bacteria via electrostatic interaction. This in turn promotes more oligomeric bile acid units that can be inserted into the membrane through hydrophobic interaction between bile acids and lipid domains. The noncovalently constructed and separable amphiphilic antimicrobials can avoid the long-term coexistence of microorganisms and antibacterial molecules in different acting modes. Therefore, the noncovalent bile acid oligomers, especially those with higher oligomerization degrees, can be a potential approach to effectively enhance antibacterial activity, improve environmental friendliness, and reduce bacterial drug resistance.

GUANIDINIIUM-CONTAINING OLIGOMER CATIONIC PROTONIC IONIC LIQUIDS

By reacting a dian epoxy oligomer with guanidinium hydrochloride, a synthesis method of guanidinium-containing cationic proton oligomeric ionic liquids (OIL) capable of condensation reactions was developed. These compounds are characterized by an amphiphilic structure combining a flexible oligoether or hydroxyl-containing guanidinium oligoether block with terminal hydroxyl-containing guanidinium fragments. These compounds are capable of supramolecular organization due to the self-association of flexible oligoether blocks with terminal hydroxyl-containing guanidinium fragments from the outside of the formed cluster. They are characterized by two glass transition temperatures, which differ significantly in magnitude. The structure formed by the flexible oligoether component is determined by its segmental mobility with the glass transition temperature in the range (70–85 °C), and the terminal guanidinium fragments are responsible for the manifestation of the cohesive nature of the glass transition of the oligomer as a whole with the glass transition temperature in the range (-70)–(-60 °C), which characteristic of classical ionic liquids. The proton conductivity of the synthesized compounds in anhydrous conditions reaches a value of 1,94·10-3 S/cm at 120 °C and is determined not by the absolute value of the introduced protons, but by their specific number in relation to the MW oligomers. The synthesized OIL are of interest as electrolytes with an anhydrous conduction mechanism and starting reagents for the synthesis of ion-containing block copolymers of various functional purposes.

High-performance arabinoglucuronoxylan-based biosurfactants for oily sludge separation

Arabinoglucuronoxylan (AGX), an important carbohydrate polymer in lignocellulosic biomass, contains many functional groups. It has excellent amphiphilic modification properties and has potential application in the separation of oily sludge. In this study, a simple strategy for producing high-performance AGX-based biosurfactants was studied and the raw AGX was extracted from bamboo by hydrothermal treatment. AGX-based biosurfactants with amphiphilic structure were produced by AGX and dodecanal succinic anhydride (DDSA) using rapid homogeneous esterification reactions in deep eutectic solvents (DES). This resulted in a significant reduction in the surface tension of the water from 72.32 to 29.76 mN·m−1. These parameters are similar to those achieved using sodium dodecyl sulfate (SDS), a widely employed synthetic surfactant. Other physicochemical properties, including foamability, emulsification activity, stability, solubilization, and detergency were significantly improved compared to the unmodified AGX, demonstrate that AGX-based biosurfactants are promising detergents for oily sludge remediation and oil recovery. The results provide a new pathway for high value utilization of arabinoglucuronoxylan.

Monitoring Cell Plasma Membrane Polarity by a NIR Fluorescence Probe with Unexpected Cell Plasma Membrane-Targeting Ability.

The cell plasma membrane, the natural barrier of a cell, plays critical roles in a mass of cell physiological and pathological processes. Therefore, revealing and monitoring the local status of the cell plasma membrane are of great significance. Herein, using a near-infrared (NIR) fluorescence probe BTCy, microenvironmental polarity in the cell plasma membrane was in situ monitored. BTCy showed sensitive and selective fluorescence decrease response at 706 nm with the increase of polarity as its polarity-responsive D-π-A structure. Most importantly, BTCy showed unexpected cell plasma membrane-targeting ability, probably due to its amphiphilic structure. With BTCy, the distinguishing imaging of cancer and normal cells was done, in which cancer cells exhibited significantly stronger signals due to their lower cell plasma membrane polarity. In addition, with the imaging of BTCy, the ferroptosis process was revealed with no significant cell plasma membrane polarity variation for the first time. Furthermore, BTCy was employed for in vivo imaging of tumor tissue in the 4T1-tumor-bearing mice. The polarity-responsive and cell plasma membrane-targeting properties of BTCy make it a useful tool for monitoring cell plasma membrane polarity variation, providing an efficient and simple method for tumor diagnosis.

Inhibiting ice recrystallization by amyloid protein fibrils

Ice recrystallization is harmful to the quality of frozen foods and the cryopreservation of cells and biological tissues, requiring biocompatible materials with ice recrystallization inhibition (IRI) activity. Emerging studies have associated IRI activity with amphiphilic structures. We propose amphiphilic amyloid protein fibrils (APFs) may be IRI-active. APFs were prepared from whey protein isolate (WPI) in water (W-APFs) and in trifluoroethanol (TFE-APFs). W-APFs and TFE-APFs were more IRI-active than WPI over a concentration range of 2.5–10.0 mg/mL. Both APFs showed stronger IRI activity at pH 3.0 than at pH 5.0, 7.0, and 10.0, which was ascribed to the effect of water dispersibility and fibril length. The reduced IRI activity of the two APFs with increasing NaCl content was caused by fibril aggregation. Ice binding by APFs was absent or very weak. Ordered water was observed for the two APFs, which might be essential for IRI activity. Our findings may lead to the use of APFs as novel ice recrystallization inhibitors.

Molecular Diversity of Linear Peptides Revealed by Transcriptomic Analysis of the Venom Gland of the Spider Lycosa poonaensis.

Spider venom is a complex mixture of bioactive components. Previously, we identified two linear peptides in Lycosa poonaensis venom using mass spectrometric analysis and predicted the presence of more linear peptides therein. In this study, a transcriptomic analysis of the L. poonaensis venom gland was conducted to identify other undetermined linear peptides in the venom. The results identified 87 contigs encoding peptides and proteins in the venom that were similar to those in other spider venoms. The number of contigs identified as neurotoxins was the highest, and 15 contigs encoding 17 linear peptide sequences were identified. Seven peptides that were representative of each family were chemically synthesized, and their biological activities were evaluated. All peptides showed significant antibacterial activity against Gram-positive and Gram-negative bacteria, although their selectivity for bacterial species differed. All peptides also exhibited paralytic activity against crickets, but none showed hemolytic activity. The secondary structure analysis based on the circular dichroism spectroscopy showed that all these peptides adopt an amphiphilic α-helical structure. Their activities appear to depend on the net charge, the arrangement of basic and acidic residues, and the hydrophobicity of the peptides.