skip to main content

Attention:

The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 11:00 PM ET on Thursday, May 23 until 2:00 AM ET on Friday, May 24 due to maintenance. We apologize for the inconvenience.


This content will become publicly available on June 22, 2024

Title: Polydots, soft nanoparticles, at membrane interfaces
Soft nanoparticles (NPs) are emerging candidates for nano medicine, particularly for intercellular imaging and targeted drug delivery. Their soft nature, manifested in their dynamics, allows translocation into organisms without damaging their membranes. A crucial step towards incorporating soft dynamic NPs in nano medicine, is to resolve their interrelation with membranes. Here using atomistic molecular dynamics (MD) simulations we probe the interaction of soft NPs formed by conjugated polymers with a model membrane. These NPs, often termed polydots, are confined to their nano dimensions without any chemical tethers, forming dynamic long lived nano structures. Specifically, polydots formed by dialkyl para poly phenylene ethylene (PPE), with a varying number of carboxylate groups tethered to the alkyl chains to tune the interfacial charge of the surface of the NP are investigated at the interface with a model membrane that consists of di-palmitoyl phosphatidylcholine (DPPC). We find that even though polydots are controlled only by physical forces, they retain their NP configuration as they transcend the membrane. Regardless of their size, neutral polydots spontaneously penetrate the membrane whereas carboxylated polydots must be driven in, with a force that depends on the charge at their interface, all without significant disruption to the membrane. These fundamental results provide a means to control the position of the nanoparticles with respect to the membrane interfaces, which is key to their therapeutic use.  more » « less
Award ID(s):
1905407 1725573
NSF-PAR ID:
10438648
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
RSC Advances
Volume:
13
Issue:
28
ISSN:
2046-2069
Page Range / eLocation ID:
19227 to 19234
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ConspectusGold nanoparticles (AuNPs) exhibit unique size- and shape-dependent properties not obtainable at the macroscale. Gold nanorods (AuNRs), with their morphology-dependent optical properties, ability to convert light to heat, and high surface-to-volume ratios, are of great interest for biosensing, medicine, and catalysis. While the gold core provides many fascinating properties, this Account focuses on AuNP soft surface coatings, which govern the interactions of nanoparticles with the local environments. Postmodification of AuNP surface chemistry can greatly alter NP colloidal stability, nano-bio interactions, and functionality. Polyelectrolyte coatings provide controllable surface-coating thickness and charge, which impact the composition of the acquired corona in biological settings. Covalent modification, in which covalently bound ligands replace the original capping layer, is often performed with thiols and disulfides due to their ability to replace native coatings. N-heterocyclic carbenes and looped peptides expand the possible functionalities of the ligand layer.The characterization of surface ligands bound to AuNPs, in terms of ligand density and dynamics, remains a challenge. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for understanding molecular structures and dynamics. Our recent NMR work on AuNPs demonstrated that NMR data were obtainable for ligands on NPs with diameters up to 25 nm for the first time. This was facilitated by the strong proton NMR signals of the trimethylammonium headgroup, which are present in a distinct regime from other ligand protons’ signals. Ligand density analyses showed that the smallest AuNPs (below 4 nm) had the largest ligand densities, yet spin–spin T2 measurements revealed that these smallest NPs also had the most mobile ligand headgroups. Molecular dynamics simulations were able to reconcile these seemingly contradictory results.While NMR spectroscopy provides ligand information averaged over many NPs, the ligand distribution on individual particles’ surfaces must also be probed to fully understand the surface coating. Taking advantage of improvements in electron energy loss spectroscopy (EELS) detectors employed with scanning transmission electron microscopy (STEM), a single-layer graphene substrate was used to calibrate the carbon K-edge EELS signal, allowing quantitative imaging of the carbon atom densities on AuNRs with sub-nanometer spatial resolution. In collaboration with others, we revealed that the mean value for surfactant-bilayer-coated AuNRs had 10–30% reduced ligand density at the ends of the rods compared to the sides, confirming prior indirect evidence for spatially distinct ligand densities.Recent work has found that surface ligands on nanoparticles can, somewhat surprisingly, enhance the selectivity and efficiency of the electrocatalytic reduction of CO2 by controlling access to the active site, tuning its electronic and chemical environment, or denying entry to impurities that poison the nanoparticle surface to facilitate reduction. Looking to the future, while NMR and EELS are powerful and complementary techniques for investigating surface coatings on AuNPs, the frontier of this field includes the development of methods to probe the surface ligands of individual NPs in a high-throughput manner, to monitor nano-bio interactions within complex matrices, and to study structure–property relationships of AuNPs in biological systems. 
    more » « less
  2. null (Ed.)
    Designing of nanoparticles (NPs) for biomedical applications or mitigating their cytotoxic effects requires microscopic understanding of their interactions with cell membranes. Such insight is best obtained by studying model biomembranes which, however, need to replicate actual cell membranes, especially their compositional heterogeneity and charge. In this work we have investigated the role of lipid charge density and packing of phase separated Langmuir monolayers in the penetration and phase specificity of charged quantum dot (QD) binding. Using an ordered and anionic charged lipid in combination with uncharged but variable stiffness lipids we demonstrate how the subtle interplay of zwitterionic lipid packing and anionic lipid charge density can affect cationic nanoparticle penetration and phase specific binding. Under identical subphase pH, the membrane with higher anionic charge density displays higher NP penetration. We also observe coalescence of charged lipid rafts floating amidst a more fluidic zwitterionic lipid matrix due to the phase specificity of QD binding. Our results suggest effective strategies which can be used to design NPs for diverse biomedical applications as well as to devise remedial actions against their harmful cytotoxic effects especially against respiratory diseases. 
    more » « less
  3. null (Ed.)
    Using molecular dynamics simulations of a coarse-grained implicit solvent model, we investigate the binding of crescent-shaped nanoparticles (NPs) on tubular lipid membranes. The NPs adhere to the membrane through their concave side. We found that the binding/unbinding transition is first-order, with the threshold binding energy being higher than the unbinding threshold, and the energy barrier between the bound and unbound states at the transition that increases with increasing the NP's arclength L np or curvature mismatch μ = R c / R np , where R c and R np are the radii of curvature of the tubular membrane and the NP, respectively. Furthermore, we found that the threshold binding energy increases with increasing either L np or μ . NPs with curvature larger than that of the tubule ( μ > 1) lie perpendicularly to the tubule's axis. However, for μ smaller than a specific arclength-dependent mismatch μ *, the NPs are tilted with respect to the tubule's axis, with the tilt angle that increases with decreasing μ . We also investigated the self-assembly of the NPs on the tubule at relatively weak adhesion strength and found that for μ > 1 and high values of L np , the NPs self-assemble into linear chains, and lie side-by-side. For μ < μ * and high L np , the NPs also self-assemble into chains, while being tilted with respect to the tubule's axis. 
    more » « less
  4. The initial interactions of engineered nanoparticles (NPs) with living cells are governed by physicochemical properties of the NP and the molecular composition and structure of the cell membrane. Eukaryotic cell membranes contain lipid rafts – liquid-ordered nanodomains involved in membrane trafficking and molecular signaling. However, the impact of these membrane structures on cellular interactions of NPs remains unclear. Here we investigate the role of membrane domains in the interactions of primary amine-terminated quantum dots (Qdots) with liquid-ordered domains or lipid rafts in model membranes and intact cells, respectively. Using correlative atomic force and fluorescence microscopy, we found that the Qdots preferentially localized to boundaries between liquid-ordered and liquid-disordered phases in supported bilayers. The Qdots also induced holes at these phase boundaries. Using super resolution fluorescence microscopy (STORM), we found that the Qdots preferentially co-localized with lipid rafts in the membrane of intact trout gill epithelial cells – a model cell type for environmental exposures. Our observations uncovered preferential interactions of amine-terminated Qdots with liquid-ordered domains and their boundaries, possibly due to membrane curvature at phase boundaries creating energetically favorable sites for NP interactions. The preferential interaction of the Qdots with lipid rafts supports their potential internalization via lipid raft-mediated endocytosis and interactions with raft-resident signaling molecules. 
    more » « less
  5. In this study, hydrophilic silica nanoparticles (Si NPs) were used to modify α-alumina tubular membranes to improve their performance in terms of flux, oil rejection, and anti-fouling properties. Our work focuses on enhancing membrane performance, particularly for difficult applications such as produced water treatment. The prepared membranes were applied for oil-in-water emulsion treatment. After coating hydrophilic Si NPs, the oil contact angle improved from 133.8° to 171.4°. To prevent Si NPs from leaching off the surface of α-alumina tubular membranes, polyvinyl alcohol was used to coat the membranes as a pre-treatment step before Si NP modification. After coating the membrane with Si NPs, the roughness of the membrane surface decreased, likely leading to less fouling. After coating Si NPs, Total Organic Carbon rejection increased from 93.1% for pristine α-alumina tubular membranes to 97.7% for silica-modified membranes because of hydrophilic improvements of the modified membranes. The Si NP coating improved the anti-fouling property of membranes with the flux recovery ratio increasing from 71.3% for pristine α-alumina tubular membranes to 85.9% for silica-modified membranes. Scanning Electron Microscopy, Energy- dispersive X-ray spectroscopy, oil contact angle, and Atomic Force Microscopy characterization tests were done. The tests showed successful Si NPs impregnation and altered wettability. 
    more » « less