skip to main content

Explore Research Products in the NSF-PAR

Title: Influence of sensor composition on nanoparticle and protein interaction with supported lipid bilayers
Supported lipid bilayers are often used as model systems for studying interactions of biological membranes with protein or nanoparticles. A supported lipid bilayer is a phospholipid bilayer built on a solid substrate. The latter is typically made of silica or a metal oxide due to the ease of its formation and range of compatible measurement techniques. Recently, a solvent-assisted method involving supported lipid bilayer formation has allowed the extension of compatible substrate materials to include noble metals such as gold. Here, we examine the influence of substrate composition (SiO2 vs Au) on the interactions between anionic ligand-coated Au nanoparticles or cytochrome c and zwitterionic supported lipid bilayers using quartz crystal microbalance with dissipation monitoring. We find that anionic nanoparticles and cytochrome c have higher adsorption to bilayers formed on Au relative to those on SiO2 substrates. We examine the substrate-dependence of nanoparticle adsorption with DLVO theory and all-atom simulations, and find that the stronger attractive van der Waals and weaker repulsive electrostatic forces between anionic nanoparticles and Au substrates vs anionic nanoparticles and SiO2 substrates could be responsible for the change in adsorption observed. Our results also indicate that the underlying substrate material influences the degree to which nanoscale analytes interact with supported lipid bilayers; therefore, interpretation of the supported lipid bilayer model system should be conducted with understanding of support properties.  more » « less
Award ID(s):
2001611
NSF-PAR ID:
10464933
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Environmental Science: Nano
ISSN:
2051-8153
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ( , Langmuir)
    null (Ed.)
    Supported lipid bilayers (SLBs) have proven to be valuable model systems for studying the interactions of proteins, peptides, and nanoparticles with biological membranes. The physicochemical properties (e.g., topography, coating) of the solid substrate may affect the formation and properties of supported phospholipid bilayers, and thus, subsequent interactions with biomolecules or nanoparticles. Here, we examine the influence of support coating (SiO2 vs Si3N4) and topography [sensors with embedded vs protruding gold nanodisks for nanoplasmonic sensing (NPS)] on the formation and subsequent interactions of supported phospholipid bilayers with the model protein cytochrome c and with cationic polymer-wrapped quantum dots using quartz crystal microbalance with dissipation monitoring and NPS techniques. The specific protein and nanoparticle were chosen because they differ in the degree to which they penetrate the bilayer. We find that bilayer formation and subsequent non-penetrative association with cytochrome c were not significantly influenced by substrate composition or topography. In contrast, the interactions of nanoparticles with SLBs depended on the substrate composition. The substrate-dependence of nanoparticle adsorption is attributed to the more negative zeta-potential of the bilayers supported by the silica vs the silicon nitride substrate and to the penetration of the cationic polymer wrapping the nanoparticles into the bilayer. Our results indicate that the degree to which nanoscale analytes interact with SLBs may be influenced by the underlying substrate material. 
    more » « less
  2. ; ; ; ; ; ( , ACS Nano)
    null (Ed.)
    A mechanistic understanding of the influence of the surface properties of engineered nanomaterials on their interactions with cells is essential for designing materials for applications such as bioimaging and drug delivery as well as for assessing nanomaterial safety. Ligand-coated gold nanoparticles have been widely investigated because their highly tunable surface properties enable investigations into the effect of ligand functionalization on interactions with biological systems. Lipophilic ligands have been linked to adverse biological outcomes through membrane disruption, but the relationship between ligand lipophilicity and membrane interactions is not well understood. Here, we use a library of cationic ligands coated on 2 nm gold nanoparticles to probe the impact of ligand end group lipophilicity on interactions with supported phosphatidylcholine lipid bilayers as a model for cytoplasmic membranes. Nanoparticle adsorption to and desorption from the model membranes were investigated by quartz crystal microbalance with dissipation monitoring. We find that nanoparticle adsorption to model membranes increases with ligand lipophilicity. The effects of ligand structure on gold nanoparticle attachment were further analyzed using atomistic molecular dynamics simulations, which showed that the increase in ligand lipophilicity promotes ligand intercalation into the lipid bilayer. Together, the experimental and simulation results could be described by a two-state model that accounts for the initial attachment and subsequent conversion to a quasi-irreversibly bound state. We find that only nanoparticles coated with the most lipophilic ligands in our nanoparticle library undergo conversion to the quasi-irreversible state. We propose that the initial attachment is governed by interaction between the ligands and phospholipid tail groups, whereas conversion into the quasi-irreversibly bound state reflects ligand intercalation between phospholipid tail groups and eventual lipid extraction from the bilayer. The systematic variation of ligand lipophilicity enabled us to demonstrate that the lipophilicity of cationic ligands correlates with nanoparticle-bilayer adsorption and suggested that changing the nonpolar ligand R group promotes a mechanism of ligand intercalation into the bilayer associated with irreversible adsorption. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; ( , Environmental Science: Nano)
    We use diamond nanoparticles (DNPs) wrapped in the cationic polyelectrolyte poly(allylamine) hydrochloride (PAH) and bilayers composed of either pure DOPC or a mixture of DOPC/DOPG to investigate the influence of membrane phospholipid composition and net surface charge on nanoparticle-membrane interactions and the extent of nanoparticle adhesion to supported phospholipid bilayers. Our results show that in all cases electrostatic attractions between the negatively charged bilayer and cationic PAH-DNP were responsible for the initial attachment of particles, and the lateral electrostatic repulsion between adsorbed particles on the bilayer surface determined the final extent of PAH-DNP attachment. Upon attachment, NPs attract lipids by the contact ion pairing between the ammonium groups on PAH and phosphate and glycerol groups on the lipids and acquire a lipid corona. Lipid corona formation on the PAH-DNP reduces the effective charge density of the particle and is in fact a key factor determining the final extent of NP attachment to the bilayer. Incorporation of DOPG to the bilayer leads to a decrease in efficiency and final extent of attachment compared to DOPC alone. The reduction in PAH-DNP attachment in the presence of DOPG is attributed to the adsorption of free PAH in equilibrium with bound PAH in the nanoparticle solution, thus reducing electrostatic attraction between PAH-DNPs and SLBs. This leads to an increase in hydrogen bonding interactions between lipid headgroups that limits extraction of phospholipids from the bilayer by PAH-DNP, lessening the reduction in interparticle repulsion achieved by acquisition of a lipid corona. Our results indicate that the inclusion of charged phospholipids in SLBs changes bilayer rigidity and stability and hinders the attachment of PAH-DNPs by preventing lipid extraction from the bilayer. 
    more » « less
  4. ; ( , Soft Matter)
    In this study, we report the complex effects of charged lipids on the interaction between amphiphilic Janus nanoparticles and lipid bilayers. Janus nanoparticles are cationic on one hemisphere and hydrophobic on the other. We show that the nanoparticles, beyond threshold concentrations, induce holes in both cationic and anionic lipid bilayers mainly driven by hydrophobic interactions. However, the formation of these defects is non-monotonically dependent on ionic lipid composition. The electrostatic attraction between the particles and anionic lipid bilayers enhances particle adsorption and lowers the particle concentration threshold for defect initiation, but leads to more localized membrane disruption. Electrostatic repulsion leads to reduced particle adsorption on cationic bilayers and extensive defect formation that peaks at intermediate contents of cationic lipids. This study elucidates the significant role lipid composition plays in influencing how amphiphilic Janus nanoparticles interact with and perturb lipid membranes. 
    more » « less
  5. ; ( , Chemical Science)
    Many intrinsically disordered peptides have been shown to undergo liquid–liquid phase separation and form complex coacervates, which play various regulatory roles in the cell. Recent experimental studies found that such phase separation processes may also occur at the lipid membrane surface and help organize biomolecules during signaling events; in some cases, phase separation of proteins at the membrane surface was also observed to lead to significant remodeling of the membrane morphology. The molecular mechanisms that govern the interactions between complex coacervates and lipid membranes and the impacts of such interactions on their structure and morphology, however, remain unclear. Here we study the coacervation of poly-glutamate (E 30 ) and poly-lysine (K 30 ) in the presence of lipid bilayers of different compositions. We carry out explicit-solvent coarse-grained molecular dynamics simulations by using the MARTINI (v3.0) force-field. We find that more than 20% anionic lipids are required for the coacervate to form stable contact with the bilayer. Upon wetting, the coacervate induces negative curvature to the bilayer and facilitates local lipid demixing, without any peptide insertion. The magnitude of negative curvature, extent of lipid demixing, and asphericity of the coacervate increase with the concentration of anionic lipids. Overall, we observe a decrease in the number of contacts among the polyelectrolytes as the droplet spreads over the bilayer. Therefore, unlike previous suggestions, interactions among polyelectrolytes do not constitute a driving force for the membrane bending upon wetting by the coacervate. Rather, analysis of interaction energy components suggests that bending of the membrane is favored by enhanced interactions between polyelectrolytes with lipids as well as with counterions. Kinetic studies reveal that, at the studied polyelectrolyte concentrations, the coacervate formation precedes bilayer wetting. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email