Amphiphilic Structure Research Articles

Structural modification of lipid membranes by polyphenols: A fluorescence spectroscopy study.

The present study investigates the molecular mechanisms of polyphenol-lipid interactions and their impact on membrane properties. Using pyrene and DPH as reporter molecules, we examined the impact of quercetin, curcumin, gallic, and salicylic acids on membranes composed of phosphatidylcholine (PC) and its mixtures with phosphatidylglycerol (PG), cardiolipin (CL), and cholesterol (Chol). Quercetin was found to increase the lipid order without affecting the lipid bilayer free volume, indicating interactions near the membrane surface. In turn, curcumin exhibited more complex effects, reducing free volume in PC but increasing it in PG vesicles, reflecting its amphiphilic structure and variable penetration depth. Gallic and salicylic acids selectively increased free volume at the membrane core without influencing lipid order at the upper regions of lipid bilayer. The results obtained demonstrate that polyphenol structure and lipid composition dictate the resultant pattern of polyphenol-membranes interactions, which may have implications for drug delivery and nutraceutical design.

Amphibian-Derived Antimicrobial Peptides: Essential Components of Innate Immunity and Potential Leads for New Antibiotic Development.

Like other vertebrates, amphibians possess innate and adaptive immune systems. At the center of the adaptive immune system is the Major Histocompatibility Complex. The important molecules of innate immunity are antimicrobial peptides (AMPs). These peptides are secreted by granular glands in the skin and protect the animal against microorganisms entering its body through the skin. AMPs offer an effective and rapid defense against pathogenic microorganisms and have cationic and amphiphilic structures. These peptides are small gene-encoded molecules of 8-50 amino acid residues synthesized by ribosomes. These small molecules typically exhibit activity against bacteria, viruses, fungi, and even cancer cells. It is known that today's amphibian AMPs originated from a common precursor gene 150 million years ago and that the origin of these peptides is preprodermaseptins. Today, antibiotic resistance has occurred due to the incorrect use of antibiotics. Traditional antibiotics are becoming increasingly inadequate. AMPs are considered promising candidates for the development of new-generation antibiotics. Therefore, new antibiotic discoveries are needed. AMPs are suitable molecules for new-generation antibiotics that are both fast and have different killing mechanisms. One of the biggest problems in the clinical applications of AMPs is their poor stability. AMPs generally have limited tropical applications because they are sensitive to protease degradation. Coating these peptides with nanomaterials to make them more stable can solve this problem.

Research progress on the synthesis process, detection method, pharmacological effects and application of glycocholic acid.

This review aims to summarize the research progress of glycocholic acid to promote its broader development and application. This article collects relevant literature from databases such as Science Direct, PubMed, Web of Science, Google Scholar and CNKI from the establishment to 2024, systematically organizing and analyzing aspects of glycocholic acid including its physicochemical properties, synthesis and extraction techniques, detection methods, pharmacological effects, mechanisms of action, clinical research, and application as an excipient. Glycocholic acid, as a key conjugated component in bile acids, exhibits various pharmacological effects such as anti-inflammatory and antioxidant activities. Nevertheless, current research on glycocholic acid is insufficient, with synthesis techniques requiring improvement, limited application of detection technologies, and a need for in-depth exploration of its pharmacological mechanisms. Due to its amphiphilic molecular structure, glycocholic acid is primarily used as a pharmaceutical excipient. This review summarizes the existing research on glycocholic acid, indicating that future research should strengthen work in this field, including improving synthesis processes and enhancing the sensitivity of detection technologies, to provide a scientific basis for the development of new formulations and drug combinations, thereby promoting the advancement of traditional Chinese medicine.

Impact of the hydrophilic-lipophilic balance of free-base and Zn(II) tricationic pyridiniumporphyrins and irradiation wavelength in PDT against the melanoma cell lines.

The amphiphilic and asymmetric structure of porphyrins, when used as photosensitizers (PSs) for photodynamic therapy (PDT), has been shown through numerous previous studies to be a very important property that facilitates their entry into cells, which improves their efficiency in PDT. In this work, two groups of cationic AB3 pyridiniumporphyrins, free-base and chelated with Zn(II), both substituted with alkyl chains of various lengths, were studied in PDT on melanoma cell lines. The aim was to investigate the impact of hydrophilic-lipophilic balance and Zn(II) chelation, and the importance of matching the irradiation wavelength to the optical properties of the PS on in vitro PDT efficiency. Therefore, spectroscopic studies, singlet oxygen production and lipophilicity as well as cellular uptake, localization and cytotoxicity studies of the two series of porphyrins were performed. In both series of porphyrins, the longest alkyl chain (17C-atoms long) enables the greatest internalization of the PS. Chelation with Zn(II) resulted in better physicochemical properties, but slower cellular internalization. As expected, free-base porphyrins were more PDT efficient than their Zn(II) complexes after 30-min photoactivation by low-fluence (2mW/cm2) red light (643nm). However the use of orange light (606nm) with the same fluence rate was more suitable for Zn(II) porphyrins and resulted in similar overall toxicity to their free-base analogues with similar lipophilicity. Although the highest phototoxicity was achieved with the PSs carrying the longest alkyl chain, TMPyP3-C13H27 and Zn(II)-TMPyP3-C13H27 proved to be the most promising candidates for use in PDT as they exhibit high phototoxicity, but also greater selectivity towards melanoma cell lines (MeWo and A375) compared to fibroblasts (HDF).

Design of Extruded Nanostructured Composites via Decoupling of the Cellulose Nanofibril/Poly(butylene adipate-co-terephthalate) Interface.

The full exploitation of the outstanding mechanical properties of cellulose nanofibrils (CNFs) as potential reinforcements in nanocomposite materials is limited by the poor interactions at the CNF-polymer matrix interface. Within this work, tailor-made copolymers were designed to mediate the interface between CNFs and biodegradable poly(butylene adipate-co-terephthalate) (PBAT), and their effect on extruded nanocomposite performance was tested. For this purpose, two well-defined amphiphilic anchor-tail diblock copolymer structures were compared, with a fixed anchor block length and a large difference in the hydrophobic tail block length. The aim was to evaluate the impact of the copolymers' chain length on the nanocomposite interface. The presence of amphiphilic diblock copolymers significantly improved the mechanical properties compared to those of PBAT nanocomposites containing unmodified CNFs. In particular, the copolymer with a longer tail was more effective for CNF-PBAT dispersion interactions, leading to a 65% increase of Young's modulus of neat PBAT, while retaining high deformability (670%). The results provide insights into the effectiveness of a waterborne third component at the CNF-matrix interface and its structure-property relationship.

Molecular dynamics simulation of microscopic interaction mechanism between oil–water interface by modified graphene oxide oil displacement agent

With the increasing worldwide energy demand, enhanced oil recovery (EOR) is becoming more critical for oil fields. In recent years, the rise of nanotechnology has provided a new direction for developing oil repellents in low-permeability reservoirs, and the new nanomaterial-modified graphene oxide (MGO) has demonstrated good EOR performance in oil and gas field development. In this work, molecular dynamics simulations were carried out to investigate the influence of MGO on the interfacial tension (IFT) of oil water and its microscopic interaction mechanism. The impact of different grafting ratios and lengths of modified NPs on the interfacial properties of oil–water interfaces and their mechanisms were further analyzed. Simulation results indicate that, due to their amphiphilic structure, they are attracted to the oil phase and can spontaneously migrate to the oil–water interface. They form a dense monolayer film structure at the oil–water interface, reducing the IFT from 52.08 mN·m−1 thickness to 28.03 mN·m−1 by increasing the thickness of the oil–water interface. The most significant reduction in IFT was observed when MGO was grafted with sixteen-alkyl-long chains. The molecular-level insights gained from this study can provide valuable guidance for designing modified nanoparticles suitable for EOR applications.

Facile Synthesis of Thermoresponsive Alternating Copolymers with Tunable Phase-Transition Temperatures.

A series of novel amphiphilic alternating CPEG copolymers were synthesized through an amine-epoxy click reaction comprising aliphatic amine and polyethylene glycol diglycidyl ether (PEGDE). These polymers were characterized in detail via nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) to confirm the successful synthesis. Due to their amphiphilic structure, these polymers display thermoresponsiveness, with tunable cloud points (Tcps) that are adjustable from 20.8 °C to 46.8 °C by altering the side-chain length of the aliphatic amine, varying the mixing ratios of copolymers, the solution's pH, and salt additions. This tunable thermoresponsive behavior positions CPEG copolymers as promising candidates for a range of functional material applications.

Antimicrobial Peptides from Frogs of the Glandirana Genus

Glandirana is a genus of frogs that includes G. rugosa, G. emeljanovi, G. minima, G. tientaiensis, G. susurra, G. nakamurai and G. reliquia. These frogs produce antimicrobial peptides (AMPs), which are endogenous antibiotics that possess antibacterial, antifungal, antiviral and anti-endotoxin activity and help keep the hosts free from infections. In these activities, microbial death is promoted by membranolytic mechanisms that are mediated by the cationic charge and amphiphilic α-helical structures of these peptides. In general, these peptides are selective for microbes, showing low levels of hemolytic and cytotoxic activity, as well as possessing other biological activities, including anticancer, antioxidative and insulinotrophic action. In this review, a brief overview of AMPs with a focus on those from amphibians is provided, along with the phylogeny and nomenclature of frogs and AMPs from the Glandirana genus. This review then provides a comprehensive, in-depth description of the antimicrobial and other biological activities of all AMPs produced by known frogs of the Glandirana for the period 1994 to 2024. This description includes a detailed discussion of the structure/function relationships and mechanisms involved in the membrane interactions that drive these biological activities, with comparisons between AMPs from the same frog and between frogs across the genus. Based on their biological properties, AMPs from frogs of the Glandirana genus have been proposed for investigation as potential therapeutic agents, such as in the treatment of cancers and diabetes, as well as antimicrobial agents in areas, including crop protection, the food industry and oral hygiene.

Glycyrrhizic acid-based multifunctional nanoplatform for tumor microenvironment regulation.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.

Oxaliplatin-loaded amphiphilic hyaluronic acid nanohydrogel formed via interfacial reactions enhances the therapeutic effect of targeted tumor

Hyaluronic acid (HA) nanogels have attracted widespread attention, aiming to improve cancer treatment paradigms and overcome the limitations of free-form drugs. However highly hydrophilic nature of HA nanogels limits their potential application where amphiphilic interactions are required for the delivery of hydrophobic drugs. In this study, we developed amphiphilic structure oxaliplatin (OXA) loaded oligo-hyaluronic acid (oHA)-PEG-Octane nanogel using stable disulfide bonds with ultrasonic re-emulsion method. 1,8-Mercaptooctane present in the organic phase underwent crosslinking with sulfhydryl groups conjugated on oHA and PEG in the inner aqueous phase through interfacial reactions, resulting in the formation of an amphiphilic structure of the nanogels. The nanogels demonstrated uniform size, stability, excellent biocompatibility, and achieved a high drug-loading capacity of 10.8 %. OXA NGs targeted tumor cells through CD44-mediated endocytosis, disassembled under the influence of high glutathione (GSH) levels within the tumor microenvironment (TME) and released OXA inside the reductive cytosol to trigger immunogenic cell death (ICD) of tumor cells. In vivo experiments showed OXA NGs could inhibit tumor growth. Furthermore, the amphiphilic hyaluronic acid nanohydrogel may have clinical potential due to its ability to accommodate various therapeutic agents; therefore, OXA NGs are a potential candidate for clinical translation.

Lipoic Acid Nanoparticles Exert Effective Antiatherosclerosis Effects through Anti-Inflammatory and Antioxidant Pathways.

Oxidative stress and inflammation are key pathological features of atherosclerotic plaques. Numerous nanomedicines have been developed to alleviate oxidative stress and reduce inflammation within plaques. However, nonbioactive carrier materials reduce the bioavailability of nanomedicines and may pose potential biological toxicity. In this study, we utilized the unique amphiphilic chemical structure of lipoic acid (LA) to prepare LA nanoparticles (LA NPs) via a self-assembly method. Leveraging the inherent anti-inflammatory and antioxidant properties of LA, these NPs were used for the treatment of atherosclerosis. In an inflammatory macrophage model, LA NPs exhibited superior anti-inflammatory activity compared to free LA. Through ultrasound imaging and pathological methods, we discovered that LA NPs demonstrated nice antiatherosclerotic effects in an atherosclerotic mice model. Immunofluorescence analysis further indicated that the antiatherosclerotic effects of LA were associated with the alleviation of oxidative stress within the plaques, reduced macrophage infiltration, and downregulation of inflammatory cytokine levels. Therefore, LA NPs offer a promising therapeutic strategy for the treatment of atherosclerosis.

New near-infrared fluorescent probe for imaging superoxide anion of cell membrane

Selective imaging of superoxide anion is important for understanding its role in cell membrane biology, but is often a challenging task because of the lack of an effective fluorescence probe. In this study, a new near-infrared fluorescent probe (SHX-O) that can target cell membrane was developed for imaging superoxide anion. SHX-O was designed by simultaneously incorporating a sulfonated bis-indole and a diphenylphosphinyl recognition group into the hemicyanine moiety. The probe itself showed a rather weak fluorescence due to the hemicyanine’s hydroxyl substitution; however, its reaction with superoxide anion caused a large enhancement of near-infrared fluorescence at 790 nm. Moreover, SHX-O exhibited not only high selectivity for superoxide anion over other reactive oxygen species, but also specific cell membrane localization, which may be attributed to the probe’s amphiphilic structure. Using the probe, fluorescence imaging of cell membrane superoxide anion produced in the presence of xanthine oxidase and xanthine has been achieved in living cells. We believe that SHX-O may serve as a potential tool for imaging and investigating superoxide anion of cell membrane.

Close Proximity of Cholesterol Anchors in Membrane Induces the Dissociation of Amphiphilic DNA Strand from Membrane Surface.

Dynamic DNA nanotechnology is appealing for membrane surface engineering due to their versatility and programmability. To modulate the dynamic interactions between the DNA functional units immobilized on membrane surface, membrane-anchored DNA functional units often come into close proximity each other due to DNA base pairing, which also leads to the close contact of the hydrophobic anchors in membrane. However, whether the close contact of hydrophobic anchors induces the dissociation of amphiphilic DNA structures from membrane surface is not concerned. Herein, we utilized cholesterol-labelled single-stranded DNA (ssDNA) as a simplified amphiphilic DNA structure to investigate the stability of membrane anchored DNA strands upon the closely contact of cholesterol anchors. The close contact of cholesterol-labelled ssDNA molecules driven by toehold mediated strand displacement reaction leads to approximately 41 % membrane anchored ssDNA dissociation from membrane surface, indicating the proximal cholesterol anchors in membrane could reduce the anchoring stability of cholesterol-modified DNA strands. This work enhances our understanding of the interactions between amphiphilic DNA and membranes, and provides valuable insights for the design of future DNA constructs intended for applications involving dynamic DNA reactions on membrane surface.

Identification and synthesis of a long-chain antimicrobial peptide from the venom of the Liocheles australasiae scorpion.

Scorpion venom contains linear peptides without disulfide bonds in addition to peptides with disulfide bonds. Many such linear peptides have an amphiphilic α-helical structure, often with antimicrobial activity and can be classified into three groups based on their molecular size. Among them, long-chain antimicrobial peptides consisting of more than 40 residues have not been thoroughly studied due to the difficulty of synthesizing them. We have previously reported a transcriptome analysis of the venom gland of Liocheles australasiae that revealed precursor sequences of long-chain antimicrobial peptides. In the study reported here, we identified the mature structure of one such long-chain antimicrobial peptide, LaCT1, which we synthesized using chemical ligation to confirm its structure and evaluate its biological activities. The result showed that LaCT1 exhibited significant antimicrobial activity. In addition, we identified its partial peptides consisting of an N- or C-terminal region, which may be generated by enzymatic cleavage in the venom. Among them, only the peptide containing the N-terminal half region was active. LaCT1 also not only showed insecticidal activity but also synergistically enhanced the effects of another insecticidal peptide identified in L. australasiae venom as well. These results provide insights into the role of antimicrobial peptides in scorpion venom.

Interferon lambda 4 is a gut antimicrobial protein

To withstand complex microbial challenges, the mammalian gut largely depends on the secretion of diverse antimicrobial proteins. Type III interferons (IFNλs) are ordinarily considered inducible antiviral cytokines involved in intestinal immunity. Unlike other IFNλs, we found that newly identified IFNλ4 is an intestinal antibacterial protein. Large amounts of natural IFNλ4 are present in the secretory layer of the intestinal tracts of healthy piglets, which suggests that IFNλ4 is in direct physiological contact with microbial pathogens. We also identified two biochemical functions of mammalian IFNλ4, the induction of bacterial agglutination and direct microbial killing, which are not functions of the other IFNλs. Further mechanistic investigations revealed that after binding to the carbohydrate fraction of lipopolysaccharide, mammalian IFNλ4 self-assembles into bacteria-surrounding nanoparticles that agglutinate bacteria, and that its unique cationic amphiphilic molecular structure facilitates the destruction of bacterial membranes. Our data reveal features of IFNλ4 distinct from those of previously reported IFNλs and suggest that noncanonical IFNλ4 is deeply involved in intestinal immunity, beyond simply cytokine signaling.

Blue Light Controlled Supramolecular Soft Robotics of Phenylazothiazole Amphiphiles for Rapid Macroscopic Actuations.

Nature preprograms sophisticated processes in operating molecular machines at the nanoscale, amplifying the molecular motion across multiple length-scales, and controlling movements in living organisms. Supramolecular soft robotics serve as a new alternative to hard robotics, are able to transform and amplify collective motions of the supramolecularly assembled molecular machines in attaining macroscopic motions, upon photoirradiation. By taking advantage of oriented supramolecular macroscopic soft scaffold, here the first rapid macroscopic movements of supramolecular robotic materials driven by visible light are presented. Head-tail amphiphilic structure is designed with the phenylazothiazole motif as the photoswitching core. Unidirectionally aligned nanostructures of the amphiphilic phenylazothiazoles are controlled by non-invasive blue light irradiation and bends toward the light source, demonstrating a fast macroscopic actuation of supramolecular robotic systems (up to 17°s-1) in aqueous media. Through meticulous X-ray diffraction and electron microscopy analyzes, macroscopic actuation mechanism is illustrated in a tight relation to molecular geometric transformations upon photoisomerization. By elucidating the key macroscopic actuation parameters, this paves the way for the next generation design of supramolecular soft robotic systems with enhanced biomimetic actuating functions.

Antimicrobial Peptides Derived from Bacteria: Classification, Sources, and Mechanism of Action against Multidrug-Resistant Bacteria

Antimicrobial peptides (AMPs) are short, usually cationic peptides with an amphiphilic structure, which allows them to easily bind and interact with the cellular membranes of viruses, bacteria, fungi, and other pathogens. Bacterial AMPs, or bacteriocins, can be produced from Gram-negative and Gram-positive bacteria via ribosomal synthesis to eliminate competing organisms. Bacterial AMPs are vital in addressing the increasing antibiotic resistance of various pathogens, potentially serving as an alternative to ineffective antibiotics. Bacteriocins have a narrow spectrum of action, making them highly specific antibacterial compounds that target particular bacterial pathogens. This review covers the two main groups of bacteriocins produced by Gram-negative and Gram-positive bacteria, their modes of action, classification, sources of positive effects they can play on the human body, and their limitations and future perspectives as an alternative to antibiotics.

Mechanistic Insights into the Removal of Surfactant-Like Contaminants on Mesoporous Polydopamine Nanospheres from Complex Wastewater Matrices.

The detrimental environmental effects of surfactant-like contaminants (SLCs) with distinctive amphiphilic structures have garnered significant attention, particularly since perfluorooctanesulfonate was classified as a persistent organic pollutant. Despite the numerous absorbents developed for SLCs removal, the underlying interaction mechanisms remain speculative and lack experimental validation. To address this research gap, we elucidate the mechanistic insights into the selective removal of SLCs using mesoporous polydopamine nanospheres (MPDA) fabricated via a novel soft-template method. We employed low-field nuclear magnetic resonance to quantitatively characterize the hydrophilicity of the absorbents using water molecules as probes. The results demonstrated that MPDA with uniform mesopores exhibited a remarkable threefold enhancement in SLCs' adsorption capacity compared to conventional polydopamine particles via intraparticle diffusion. We further demonstrated the dominant effects of electrostatic and hydrophobic interactions on the selective removal of SLCs with MPDA by regulating the isoelectric pH value and performing a comparative analysis. The mechanism-inspired SLC-removal strategy achieved an average removal rate of 76.3% from highly contaminated wastewater. Our findings offer new avenues for applying MPDA as an efficient adsorbent and provide innovative and mechanistic insights for targeted SLC removal in complex wastewater matrices.

Teixobactin "Swapmers" with l Tail Stereochemistry Retain Antibiotic Activity.

The unusual d-l-l-d-d-l-l pattern of stereochemistry in residues 1-7 of the peptide antibiotic teixobactin is critical to its extraordinary antibiotic activity, creating an unusual amphiphilic β-sheetlike structure that is essential to its mechanism of action. The current study sought to replace the three d-amino acids in the tail with l-amino acids while maintaining amphiphilicity. We find that swapping residues d-Gln4 and d-allo-Ile5 in O-acyl isopeptide prodrugs of teixobactin permits the introduction of l-stereochemistry with retention of antibiotic activity. Nevertheless, modifying the N-terminal stereochemistry results in a loss of antibiotic activity.

Amphiphilic disodium glycyrrhizin as a co-former for ketoconazole co-amorphous systems: Biopharmaceutical properties and underlying molecular mechanisms

Co-amorphous systems (CAMs) have been extensively investigated to improve the dissolution of hydrophobic drugs. However, drug precipitation during the storage or dissolution of CAMs has still been a major challenge. Here, disodium glycyrrhizin (Na2GA) was first used as a co-former in CAMs based on its multiple hydroxyl groups and amphiphilic structure. Ketoconazole (KTZ), a BCS class II drug, was selected as a model drug. KTZ-Na2GA CAMs at mass ratios of 1:1, 1:2.5, 1:5 and 1:10 were prepared by the spray drying method and further characterised by PXRD and DSC. The 1:2.5, 1:5 and 1:10 groups exhibited significantly enhanced Cmax (all approximately 26.67-fold) and stable maintenance of supersaturation compared to the crystalline KTZ and the corresponding physical mixtures in non-sink dissolution tests, while the 1:1 group exhibited an unstable medium Cmax (all approximately 14.67-fold). The permeability tests revealed that the permeation rate of KTZ in KTZ-Na2GA CAMs under the concentration of Na2GA in solution above the critical micelle concentration (CMC) showed a significant downwards trend compared to that below CMC. The underlying molecular mechanisms were involved in molecular miscibility, hydrogen bond interactions, solubilisation and crystallisation inhibition by Na2GA. Pharmacokinetic studies demonstrated that the AUC0-∞ of KTZ in 1:1, 1:2.5, 1:5 and 1:10 groups were significantly higher than those of the crystalline KTZ group with 2.13-, 2.30-, 2.16- and 1.86-fold, respectively (p < 0.01). In conclusion, Na2GA has proven to be a promising co-former in CAMs to enhance hydrophobic drug dissolution and bioavailability. Its effect on intestinal permeation rate of drugs also deserves attention.