skip to main content


Title: Nanocomplex made up of antimicrobial metallo-supramolecules and model biomembranes – characterization and enhanced fluorescence
Antimicrobial pentatopic 2,2′:6′,2′′-terpyridines that form 3-D supramolecular hexagonal prisms with Cd 2+ through coordination driven self-assembly can be entrapped by lipid discoidal bicelles, composed of 1,2-dipalmitoyl- sn-glycero -3-phosphocholine, 1,2-dihexanoyl- sn-glycero -3-phosphocholine and 1,2-dipalmitoyl- sn-glycero -3-phospho-(1′-rac-glycerol) lipid, forming a well-defined nanocomplex. Structural characterization performed by very small angle neutron scattering, small angle X-ray scattering and transmission electron microscopy suggests that the hexagonal prisms are preferably located at the rim of bicellar discs with the hexagonal face in parallel with the bilayers, instead of face-to-face stacking. Such a configuration reduces the π−π interaction and consequently enhances the fluorescence emission. Since novel supramolecules were reported to have antibiotic functions, this study provides insight into the interactions of antimicrobial supermolecules with lipid membranes, leading to potential theranostic applications.  more » « less
Award ID(s):
1605971
NSF-PAR ID:
10296963
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Nanoscale
Volume:
13
Issue:
35
ISSN:
2040-3364
Page Range / eLocation ID:
14973 to 14979
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Techniques that can probe nanometer length scales, such as small-angle neutron scattering (SANS), have become increasingly popular to detect phase separation in membranes. But to extract the phase composition and domain structure from the SANS traces, complementary information is needed. Here, we present a SANS, calorimetry and densitometry study of a mixture of two saturated lipids that exhibits solidus–liquidus phase coexistence: 1,2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (dDPPC, tail-deuterated DPPC) and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC). With calorimetry, we investigated the phase diagram for this system and found that the boundary traces for both multilamellar vesicles (MLVs) as well as 50 nm unilamellar vesicles overlap. Because the solidus boundary was mostly inaccessible by calorimetry, we investigated it by both SANS and molecular volume measurements for a 1:1 dDPPC:DLPC lipid mixture. From the temperature behavior of the molecular volume for the 1:1 dDPPC:DLPC mixture, as well as the individual molecular volume of each lipid species, we inferred that the liquidus phase consists of only fluid-state lipids while the solidus phase consists of lipids that are in gel-like states. Using this solidus–liquidus phase model, the SANS data were analyzed with an unrestricted shape model analysis software: MONSA. The resulting fits show irregular domains with dendrite-like features as those previously observed on giant unilamellar vesicles (GUVs). The surface pair correlation function describes a characteristic domain size for the minority phase that decreases with temperature, a behavior found to be consistent with a concomitant decrease in membrane mismatch between the liquidus and solidus phases. 
    more » « less
  2. Presented herein is the first report on dipolar Janus liposomes–liposomes that contain opposite surface charges decorating the two hemispheres of the same colloidal body. Such heterogeneous organization of surface charge is achieved through cholesterol-modulated lipid phase separation, which sorts anionic/cationic lipids into coexisting liquid-ordered/liquid-disordered domains. We present optimized experimental conditions to produce these liposomes in high yields, based on the gel-assisted hydration of ternary lipid systems consisting of cholesterol, 1,2-dipalmitoyl- sn-glycero -3-phosphocholine, and 1,2-dioleoyl- sn-glycero -3-phosphocholine. The size/charge distribution and domain configuration of these liposomes are characterized in detail by confocal fluorescence microscopy, nanosphere binding and zeta potential measurements. Using confocal fluorescence microscopy, we also follow the electrokinetic motion as well as the electrostatic self-assembly of these new dipolar Janus particles. 
    more » « less
  3. The structure and dynamics of lipid membranes in the presence of extracellular macromolecules are critical for cell membrane functions and many pharmaceutical applications. The pathogen virulence-suppressing end-phosphorylated polyethylene glycol (PEG) triblock copolymer ( Pi-ABAPEG ) markedly changes the interactions with lipid vesicle membranes and prevents PEG-induced vesicle phase separation in contrast to the unphosphorylated copolymer ( ABAPEG ). Pi-ABAPEG weakly absorbs on the surface of lipid vesicle membranes and slightly changes the structure of 1,2-dimyristoyl- sn-glycero -3-phosphocholine ( DMPC ) unilamellar vesicles at 37 °C, as evidenced by small angle neutron scattering. X-ray reflectivity measurements confirm the weak adsorption of Pi-ABAPEG on DMPC monolayer, resulting in a more compact DMPC monolayer structure. Neutron spin-echo results show that the adsorption of Pi-ABAPEG on DMPC vesicle membranes increases the membrane bending modulus κ . 
    more » « less
  4. Incorporation of lipid assemblies on the surface and within pores of mesoporous silica particles provides for biomimetic approaches to analyte sensing and separations using high surface area platforms. This work investigates the effect of pore confinement on the location and the diffusivity of lipid assemblies in mesoporous silica spherical particles (SBAS) as a function of nanopore diameters (nonporous, 3.0, 5.4, and 9.1 nm), which span the range of the thickness of the 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine lipid bilayer (≈4 nm). Large‐diameter SBAS are imaged with sufficient spatial resolution to distinguish lipids at the exterior surface and in the center of the particles. Lipids incorporated on the silica by evaporation deposition exist as exterior lipid bilayers on all particles and lipid assemblies in the pores of 5.4 and 9.1 nm pore diameter materials. Lipid diffusivity increases with pore size and decreases in the presence of bilayer tethering functional groups. Lipid diffusivity in the core of the particles is similar to the surface diffusivity, consistent with long‐range mobility in accessible, ordered (but randomly oriented) mesopores of SBAS materials. This work presents a framework for interpreting high density loading of lipid bilayers and their function within mesoporous materials.

     
    more » « less
  5. Abstract

    Redox probe transport through supported lipid bilayers and nanopore‐confined lipid assemblies on silica thin films is examined using electrochemical impedance spectroscopy (EIS). These supported lipid systems are emerging biomimetic separation and sensor platforms. The ability to quantify the accessibility of the pore structure of the mesoporous silica thin films is demonstrated, which is essential for the incorporation of carriers into the lipids for selective solute transport. Redox probe molecules with varying hydrophilicity are used to compare ion transport in supported lipid pore‐spanning bilayers (enveloped bilayers) and novel lipid filled pores of mesoporous silica thin films. The films feature orthogonally oriented 8–10 nm cylindrical nanopores formed by deposition of P123‐templated silica sols onto chemically modified fluorine‐doped tin oxide. Nanopore accessibility is confirmed by EIS with hydrophilic probe 1,1′‐ferrocenedimethanol (FDM). Filling the pores with lipid 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine results in a superior barrier (with roughly 1/9 the permeability) to transport of FDM compared to fragile enveloped lipid bilayers deposited by vesicle fusion. The pore‐confined lipids not only provide a better barrier to FDM, but also a better pathway for the transport across the films of a hydrophobic redox probe 1,1′‐dioctadecyl‐4,4′‐bipyridinium dibromide, with an ideal transport selectivity of 11 compared to FDM.

     
    more » « less