While noncovalent forces typically drive lipid vesicle adsorption and rupture to form supported lipid bilayer (SLB) coatings on inorganic surfaces, this strategy only works on a few materials with suitable energetics such as SiO2. The use of coordination chemistry between inverse-phosphocholine (PC) lipid headgroups and surfaces has emerged as a promising strategy to enable SLB formation on other materials such as TiO2 based on covalent forces. However, until now, a cohesive picture of how noncovalent and covalent forces jointly contribute to the latter SLB formation process has been lacking. Herein, we investigated inverse-PC lipid vesicle adsorption onto TiO2 and SiO2 surfaces and discovered how adsorption pathways can be controlled by tuning the balance of noncovalent and covalent forces. On TiO2, SLB formation depended on two key factors: (1) favorable noncovalent forces to facilitate initial vesicle adsorption; and (2) a critical density of lipid-TiO2 coordinate bonds to enable sufficient vesicle deformation triggering fusion and rupture. In other cases, either no adsorption or intact vesicle adsorption without rupture occurred even when coordinate bonds were present. Conversely, on SiO2, conditions were identified to support inverse-PC lipid adsorption whereas vesicles were repelled otherwise. The experimental results were supported by interfacial force modeling and our findings demonstrate how a subtle interplay of noncovalent and covalent forces plays a deterministic role in modulating lipid self-assembly pathways.
The addition of single-chain lipid amphiphiles such as antimicrobial fatty acids and monoglycerides to confined, two-dimensional phospholipid bilayers can trigger the formation of three-dimensional membrane morphologies as a passive means to regulate stress. To date, relevant experimental studies have been conducted using pure phospholipid compositions, and extending such insights to more complex, biologically relevant lipid compositions that include phospholipids and sterols is warranted because sterols are important biological mediators of membrane stress relaxation. Herein, using the quartz crystal microbalance-dissipation (QCM-D) technique, we investigated membrane remodeling behaviors triggered by the addition of sodium dodecyl sulfate (SDS), lauric acid (LA), and glycerol monolaurate (GML) to supported lipid bilayers (SLBs) composed of phospholipid and cholesterol mixtures. The SLB platforms were prepared by the solvent-assisted lipid bilayer method in order to form cholesterol-rich SLBs with tunable cholesterol fractions (0-52 mol %). The addition of SDS or LA to fabricated SLBs induced tubule formation, and the extent of membrane remodeling was greater in SLBs with higher cholesterol fractions. In marked contrast, GML addition led to bud formation, and the extent of membrane remodeling was lower in SLBs with higher cholesterol fractions. To explain these empirical observations, we discuss how cholesterol influences the elastic (stiffness) and viscous (stress relaxation) properties of phospholipid/cholesterol lipid bilayers as well as how the membrane translocation properties of single-chain lipid amphiphiles affect the corresponding membrane morphological responses. Collectively, our findings demonstrate that single-chain lipid amphiphiles induce highly specific membrane morphological responses across both simplified and complex model membranes, and cholesterol can promote or inhibit membrane remodeling by a variety of molecular mechanisms.
Multivalent 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. Our findings reveal how varying the surface densities of streptavidin receptors in the SLB and biotin ligands in the vesicles affects the extent of nanometer-scale vesicle deformation. We also identify conditions, i.e., a critical ligand density, at which appreciable vesicle deformation began, which provides insight into how the membrane bending energy partially counterposes the multivalent binding interaction energy. These findings are generalizable to various multivalent ligand–receptor systems.
A nanoplasmonic ruler method is presented in order to measure the deformation of adsorbed, nm-scale lipid vesicles on solid supports. It is demonstrated that single adsorbed vesicles undergo greater deformation on silicon oxide over titanium oxide, offering direct experimental evidence to support membrane tension-based theoretical models of supported lipid bilayer formation.
Single-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. This need is especially evident because certain surfactants that completely disrupt planar/low-curvature membranes are appreciably less active against high-curvature membranes. Herein, we conducted quartz crystal microbalance–dissipation (QCM-D) measurements to investigate the membrane-disruptive properties of glycerol monolaurate (GML) monoglyceride and lauric acid (LA) fatty acid mixtures to rupture high-curvature, ~75 nm diameter lipid vesicle adlayers. We identified that the vesicle rupture activity of GML/LA mixtures mainly occurred above the respective critical micelle concentration (CMC) of each mixture, and that 25/75 mol% GML/LA micelles exhibited the greatest degree of vesicle rupture activity with ~100% efficiency that exceeded the rupture activity of other tested mixtures, individual compounds, and past reported values with industrial surfactants. Importantly, 25/75 GML/LA micelles outperformed 50/50 GML/LA micelles, which were previously reported to have the greatest membrane-disruptive activity towards planar model membranes. We discuss the mechanistic principles behind how antimicrobial lipid engineering can influence membrane-disruptive activity in terms of optimizing the balance between competitive membrane remodeling processes and inducing anisotropic vs. isotropic spontaneous curvature in lipid membrane systems.
The coating of solid-binding peptides (SBPs) on inorganic material surfaces holds significant potential for improved surface functionalization at nano-bio interfaces.
The use of nanoscience tools to investigate how antimicrobial lipids disrupt phospholipid membranes has greatly advanced molecular-level biophysical understanding and opened the door to new application possibilities. Until now, relevant studies have focused on even-chain antimicrobial lipids while there remains an outstanding need to investigate the membrane-disruptive properties of odd-chain antimicrobial lipids that are known to be highly biologically active. Herein, using the quartz crystal microbalance-dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) techniques, we investigated how an 11-carbon, saturated fatty acid and its corresponding monoglyceride-termed undecanoic acid and monoundecanoin, respectively-disrupt membrane-mimicking phospholipid bilayers with different nanoarchitectures. QCM-D tracking revealed that undecanoic acid and monoundecanoin caused membrane tubulation and budding from supported lipid bilayers, respectively, and were only active above their experimentally determined critical micelle concentration (CMC) values. Monoundecanoin was more potent due to a lower CMC and electrochemical impedance spectroscopy (EIS) characterization demonstrated that monoundecanoin caused irreversible membrane disruption of a tethered lipid bilayer platform at sufficiently high compound concentrations, whereas undecanoic acid only induced transient membrane disruption. This integrated biophysical approach also led us to identify that the tested 11-carbon antimicrobial lipids cause more extensive membrane disruption than their respective 12-carbon analogues at 2 × CMC, which suggests that they could be promising molecular components within next-generation antimicrobial nanomedicine strategies.
Agricultural innovation is a key component of the global economy and enhances food security, health, and nutrition. Current innovation efforts focus mainly on supporting the transition to sustainable food systems, which is expected to harness technological advances across a range of fields. In this Nano Focus, we discuss how such efforts would benefit from not only supporting farmer participation in deciding transition pathways but also in fostering the interdisciplinary training and development of entrepreneurial-minded farmers, whom we term "AgTech Pioneers", to participate in cross-sector agricultural innovation ecosystems as cocreators and informed users of developing and future technologies. Toward this goal, we discuss possible strategies based on talent development, cross-disciplinary educational and training programs, and innovation clusters to build an AgTech Pioneer ecosystem, which can help to reinvigorate interest in farming careers and to identify and address challenges and opportunities in agriculture by accelerating and applying advances in nanoscience, nanotechnology, and related fields.