Medium-chain antimicrobial lipids are promising antiviral agents to inhibit membrane-enveloped viruses such as African swine fever virus (ASFV) and influenza A virus (IAV) in livestock applications. However, current uses are limited to feed pathogen mitigation due to low aqueous solubility and the development of water-dispersible lipid formulations is needed for broader application usage. In this study, we report a water-dispersible antimicrobial lipid mixture of monoglycerides and lactylates that can inhibit ASFV and IAV and exhibits antiviral properties in drinking water and feed matrices.
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View Article and Find Full Text PDFSingle-chain lipid amphiphiles such as fatty acids and monoglycerides are promising antimicrobial alternatives to replace industrial surfactants for membrane-enveloped pathogen inhibition. Biomimetic lipid membrane platforms in combination with label-free biosensing techniques offer a promising route to compare the membrane-disruptive properties of different fatty acids and monoglycerides individually and within mixtures. Until recently, most related studies have utilized planar model membrane platforms, and there is an outstanding need to investigate how antimicrobial lipid mixtures disrupt curved model membrane platforms such as intact vesicle adlayers that are within the size range of membrane-enveloped virus particles.
View Article and Find Full Text PDFHybrid lipid bilayers (HLBs) are rugged biomimetic cell membrane interfaces that can form on inorganic surfaces and be designed to contain biologically important components like cholesterol. In general, HLBs are formed by depositing phospholipids on top of a hydrophobic self-assembled monolayer (SAM) composed of one-tail amphiphiles, while recent findings have shown that two-tail amphiphiles such as inverse phosphocholine (CP) lipids can have advantageous properties to promote zwitterionic HLB formation. Herein, we explored the feasibility of fabricating cholesterol-enriched HLBs on CP SAM-functionalized TiO surfaces with the solvent exchange and vesicle fusion methods.
View Article and Find Full Text PDFMultivalent ligand-receptor interactions between receptor-presenting lipid membranes and ligand-modified biological and biomimetic nanoparticles influence cellular entry and fusion processes. Environmental pH changes can drive these membrane-related interactions by affecting membrane nanomechanical properties. Quantitatively, however, the corresponding effects on high-curvature, sub-100 nm lipid vesicles are scarcely understood, especially in the multivalent binding context.
View Article and Find Full Text PDFCholesterol plays a critical role in modulating the lipid membrane properties of biological and biomimetic systems and recent attention has focused on its role in the functions of sub-100 nm lipid vesicles and lipid nanoparticles. These functions often rely on multivalent ligand-receptor interactions involving membrane attachment and dynamic shape transformations while the extent to which cholesterol can influence such interaction processes is largely unknown. To address this question, herein, we investigated the attachment of sub-100 nm lipid vesicles containing varying cholesterol fractions (0-45 mol %) to membrane-mimicking supported lipid bilayer (SLB) platforms.
View Article and Find Full Text PDFLTX-315 is a clinical-stage, anticancer peptide therapeutic that disrupts cancer cell membranes. Existing mechanistic knowledge about LTX-315 has been obtained from cell-based biological assays, and there is an outstanding need to directly characterize the corresponding membrane-peptide interactions from a biophysical perspective. Herein, we investigated the membrane-disruptive properties of the LTX-315 peptide using three cell-membrane-mimicking membrane platforms on solid supports, namely the supported lipid bilayer, intact vesicle adlayer, and tethered lipid bilayer, in combination with quartz crystal microbalance-dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) measurements.
View Article and Find Full Text PDFThe exceptional strength and stability of noncovalent avidin-biotin binding is widely utilized as an effective bioconjugation strategy in various biosensing applications, and neutravidin and streptavidin proteins are two commonly used avidin analogues. It is often regarded that the biotin-binding abilities of neutravidin and streptavidin are similar, and hence their use is interchangeable; however, a deeper examination of how these two proteins attach to sensor surfaces is needed to develop reliable surface functionalization options. Herein, we conducted quartz crystal microbalance-dissipation (QCM-D) biosensing experiments to investigate neutravidin and streptavidin binding to biotinylated supported lipid bilayers (SLBs) in different pH conditions.
View Article and Find Full Text PDFFunctional biointerfaces hold broad significance for designing cell-responsive medical implants and sensor devices. Solid-supported phospholipid bilayers are a promising class of biological materials to build bioinspired thin-film coatings, as they can facilitate interactions with cell membranes. However, it remains challenging to fabricate lipid bilayers on medically relevant materials such as titanium oxide surfaces.
View Article and Find Full Text PDFThere is broad interest in fabricating cell-membrane-mimicking, hybrid lipid bilayer (HLB) coatings on titanium oxide surfaces for medical implant and drug delivery applications. However, existing fabrication strategies are complex, and there is an outstanding need to develop a streamlined method that can be performed quickly at room temperature. Towards this goal, herein, we characterized the room-temperature deposition kinetics and adlayer properties of one- and two-tail phosphonic acid-functionalized molecules on titanium oxide surfaces in various solvent systems and identified optimal conditions to prepare self-assembled monolayers (SAMs), upon which HLBs could be formed in select cases.
View Article and Find Full Text PDFThe size of membrane-enveloped virus particles, exosomes, and lipid vesicles strongly impacts functional properties in biological and applied contexts. Multivalent ligand-receptor interactions involving nanoparticle shape deformation are critical to such functions, yet the corresponding effect of nanoparticle size remains largely elusive. Herein, using an indirect nanoplasmonic sensing approach, we investigated how the nanoscale size properties of ligand-modified lipid vesicles affect real-time binding interactions, especially vesicle deformation processes, with a receptor-modified, cell membrane-mimicking platform.
View Article and Find Full Text PDFThe enzyme-linked immunosorbent assay (ELISA) is a widely used method for protein detection and relies on the specific capture of target proteins while minimizing the nonspecific binding of other interfering proteins and biomolecules. To prevent nonspecific binding events, blocking agents such as bovine serum albumin (BSA) protein, mixtures of proteins in media such as milk or serum, and/or surfactants are typically added to ELISA plates after probe attachment and before analyte capture. Herein, we developed a streamlined ELISA strategy in which readily prepared lipid nanoparticles are utilized as the blocking agent and are added together with the probe molecule to the ELISA plate, resulting in fewer processing steps, quicker protocol time, and superior detection performance compared to conventional BSA blocking.
View Article and Find Full Text PDFMultivalent ligand-receptor interactions are critical to the function of membrane-enveloped biological and biomimetic nanoparticles, yet resulting nanoparticle shape changes are rarely investigated. Using the localized surface plasmon resonance (LSPR) sensing technique, we tracked the attachment of biotinylated, sub-100 nm lipid vesicles to a streptavidin-functionalized supported lipid bilayer (SLB) and developed an analytical model to extract quantitative details about the vesicle-SLB contact region. The experimental results were supported by theoretical analyses of biotin-streptavidin complex formation and corresponding structural and energetic aspects of vesicle deformation.
View Article and Find Full Text PDFThe irreversible formation of cholesterol monohydrate crystals within biological membranes is the leading cause of various diseases, including atherosclerosis. Understanding the process of cholesterol crystallization is fundamentally important and could also lead to the development of improved therapeutic strategies. This has driven several studies investigating the effect of the environmental parameters on the induction of cholesterol crystallite growth and the structure of the cholesterol crystallites, while the kinetics and mechanistic aspects of the crystallite formation process within lipid membranes remain poorly understood.
View Article and Find Full Text PDFThe electrochemical-based detection of uric acid (UA) is widely used for diagnostic purposes. However, various interfering species such as ascorbic acid, dopamine, and glucose can affect electrochemical signals, and hence there is an outstanding need to develop improved sensing platforms to detect UA with high selectivity. Herein, we report a pentagonal mediator-based non-enzymatic electrochemical biosensing platform to selectively measure UA in the presence of interfering species.
View Article and Find Full Text PDFCrystallization of membrane-embedded components within phospholipid bilayers represents a distinct class of phase transformation that occurs in structurally organized, molecularly crowded, and dimensionally constrained amphiphilic fluids. Using unstable supported lipid bilayers-transiently assembled via surface-mediated fusion and spreading of bicellar precursors containing supersaturating concentrations of cholesterol-we monitor here the morphological evolution and dynamics of cholesterol crystallization within the membrane media. We find that the three-dimensional (3D) crystallization of cholesterol from an unstable two-dimensional (2D) in-membrane state proceeds via well-defined sequence of intermediates, including filaments, rods, helices, and 2D rectangular plates, before transforming into three-dimensional quadrilateral crystals-characteristic triclinic habit of cholesterol monohydrate.
View Article and Find Full Text PDFMembrane-enveloped viruses are a leading cause of viral epidemics, and there is an outstanding need to develop broad-spectrum antiviral strategies to treat and prevent enveloped virus infections. In this review, we critically discuss why the lipid membrane surrounding enveloped virus particles is a promising antiviral target and cover the latest progress in nanotechnology research to design and evaluate membrane-targeting virus inhibition strategies. These efforts span diverse topics such as nanomaterials, self-assembly, biosensors, nanomedicine, drug delivery, and medical devices and have excellent potential to support the development of next-generation antiviral drug candidates and technologies.
View Article and Find Full Text PDFOriginally developed for the structural biology field, lipid bicelle nanostructures composed of long- and short-chain phospholipid molecules have emerged as a useful interfacial science tool to fabricate two-dimensional supported lipid bilayers (SLBs) on hydrophilic surfaces due to ease of sample preparation, scalability, and versatility. To improve SLB fabrication prospects, there has been recent interest in replacing the synthetic, short-chain phospholipid component of bicellar mixtures with naturally abundant fatty acids and monoglycerides, i.e.
View Article and Find Full Text PDFProtein adsorption at solid-liquid interfaces is highly relevant to a wide range of applications such as biosensors, drug delivery, and pharmaceuticals. Understanding how protein conformation in bulk solution impacts adsorption behavior is fundamentally important and could also lead to the development of improved protein-based coatings. To date, relevant studies have been conducted in aqueous solutions, while it remains largely unknown how organic solvents and more specifically solvent-induced conformational changes might influence protein adsorption.
View Article and Find Full Text PDFSerum albumins are evolutionary conserved proteins that are found in many animal species, and purified forms are widely used in biotechnology applications, such as components within surface passivation coatings and drug delivery systems. As such, there has long been interest in studying how serum albumins adsorb onto solid supports, although existing studies are limited to one or two species. Herein, we comprehensively investigated three serum albumins of bovine (BSA), human (HSA), and rat (RSA) origin, and discovered striking differences in their conformational stabilities and adsorption properties.
View Article and Find Full Text PDFSupported lipid bilayers (SLBs) are versatile cell membrane-mimicking biointerfaces for various applications such as biosensors and drug delivery systems, and there is broad interest in developing simple, cost-effective methods to achieve SLB fabrication. One promising approach involves the deposition of quasi-two-dimensional bicelle nanostructures that are composed of long-chain phospholipids and either short-chain phospholipids or detergent molecules. While a variety of long-chain phospholipids have been used to prepare bicelles for SLB fabrication applications, only two short-chain phospholipids, 1,2-dihexanoyl--glycero-3-phosphocholine and 1,2-diheptanoyl--glycero-3-phosphocholine (collectively referred to as DHPC), have been investigated.
View Article and Find Full Text PDFACS Appl Mater Interfaces
March 2020
Supported lipid membranes are versatile biomimetic coatings for the chemical functionalization of inorganic surfaces. Developing simple and effective fabrication strategies to form supported lipid membranes with micropatterned geometries is a long-standing challenge. Herein, we demonstrate how the combination of chemical lift-off lithography (CLL) and easily prepared lipid bicelle nanostructures can yield micropatterned, supported lipid membranes on gold surfaces with high pattern resolution, conformal character, and biofunctionality.
View Article and Find Full Text PDFSupported lipid bilayers (SLBs) are simplified model membrane systems that mimic the fundamental properties of biological cell membranes and allow the surface-sensitive tools to be used in numerous sensing applications. SLBs can be prepared by various methods including vesicle fusion, solvent-assisted lipid bilayer (SALB), and bicelle adsorption and are generally composed of phospholipids. Incorporating other biologically relevant molecules, such as cholesterol (Chol), into SLBs has been reported with the vesicle fusion and SALB methods, whereas it remains unexplored with the bicelle absorption method.
View Article and Find Full Text PDFThe deposition of two-dimensional bicellar disks on hydrophilic surfaces is an emerging approach to fabricate supported lipid bilayers (SLBs) that requires minimal sample preparation, works at low lipid concentrations, and yields high-quality SLBs. While basic operating steps in the fabrication protocol mimic aspects of the conventional vesicle fusion method, lipid bicelles and vesicles have distinct architectural properties, and understanding how experimental parameters affect the efficiency of bicelle-mediated SLB formation remains to be investigated. Herein, using the quartz crystal microbalance-dissipation and localized surface plasmon resonance techniques, we investigated the effect of bulk NaCl concentration on bicelle-mediated SLB formation on silicon dioxide surfaces.
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