The High-Temperature Polymorph of LiBF4.

The single-crystal-to-single-crystal phase transition is determined by using X-ray crystallography on LiBF4, resolving a longstanding ambiguity in the existence of a high-temperature polymorph of LiBF4. LiBF4 possesses an endothermic phase change at 28.2 °C with ΔH = 1180 J mol-1 and ΔS = 3.92 J mol-1K-1 based on DSC. Single-crystal X-ray diffraction shows that the low-temperature phase collected at 200 K is a twinned trigonal P system with a twin law indicating reflection through the 110 plane. The same crystal collected above the phase transition temperature at 313 K is a C-centered orthorhombic system, describable as the superposition of the two low-temperature twin geometries undergoing interconversion. The geometries of the high- and low-temperature phases are consistent with the calorimetry experiments and with previous NMR findings indicating BF4 geometric reorientations above 300 K.

A soft co-crystalline solid electrolyte for lithium-ion batteries.

Alternative solid electrolytes are the next key step in advancing lithium batteries with better thermal and chemical stability. A soft solid electrolyte, (Adpn)2LiPF6 (Adpn, adiponitrile), is synthesized and characterized that exhibits high thermal and electrochemical stability and good ionic conductivity, overcoming several limitations of conventional organic and ceramic materials. The surface of the electrolyte possesses a liquid nano-layer of Adpn that links grains for a facile ionic conduction without high pressure/temperature treatments. Further, the material can quickly self-heal if fractured and provides liquid-like conduction paths via the grain boundaries. A substantially high ion conductivity (~10-4 S cm-1) and lithium-ion transference number (0.54) are obtained due to weak interactions between 'hard' (charge dense) Li+ ions and the 'soft' (electronically polarizable) -C≡N group of Adpn. Molecular simulations predict that Li+ ions migrate at the co-crystal grain boundaries with a (preferentially) lower activation energy Ea and within the interstitial regions between the co-crystals with higher Ea values, where the bulk conductivity is a smaller but extant contribution. These co-crystals establish a special concept of crystal design to increase the thermal stability of LiPF6 by separating ions in the Adpn solvent matrix, and also exhibit a unique mechanism of ion conduction via low-resistance grain boundaries, which contrasts with ceramics or gel electrolytes.

Solvate sponge crystals of (DMF)3NaClO4: reversible pressure/temperature controlled juicing in a melt/press-castable sodium-ion conductor.

A new type of crystalline solid, termed "solvate sponge crystal", is presented, and the chemical basis of its properties are explained for a melt- and press-castable solid sodium ion conductor. X-ray crystallography and atomistic simulations reveal details of atomic interactions and clustering in (DMF)3NaClO4 and (DMF)2NaClO4 (DMF = N-N'-dimethylformamide). External pressure or heating results in reversible expulsion of liquid DMF from (DMF)3NaClO4 to generate (DMF)2NaClO4. The process reverses upon the release of pressure or cooling. Simulations reveal the mechanism of crystal "juicing," as well as melting. In particular, cation-solvent clusters form a chain of octahedrally coordinated Na+-DMF networks, which have perchlorate ions present in a separate sublattice space in 3 : 1 stoichiometry. Upon heating and/or pressing, the Na+⋯DMF chains break and the replacement of a DMF molecule with a ClO4 - anion per Na+ ion leads to the conversion of the 3 : 1 stoichiometry to a 2 : 1 stoichiometry. The simulations reveal the anisotropic nature of pressure induced stoichiometric conversion. The results provide molecular level understanding of a solvate sponge crystal with novel and desirable physical castability properties for device fabrication.

A Metal-Organic Framework Thin Film for Selective Mg2+ Transport.

The incompatibility between the anode and the cathode chemistry limits the used of Mg as an anode. This issue may be addressed by separating the anolyte and the catholyte with a membrane that only allows for Mg2+ transport. Mg-MOF-74 thin films were used as the separator for this purpose. It was shown to meet the needs of low-resistance, selective Mg2+ transport. The uniform MOF thin films supported on Au substrate with thicknesses down to ca. 202 nm showed an intrinsic resistance as low as 6.4â€…Ω cm2 , with the normalized room-temperature ionic conductivity of ca. 3.17×10-6  S cm-1 . When synthesized directly onto a porous anodized aluminum oxide (AAO) support, the resulting films were used as a standalone membrane to permit stable, low-overpotential Mg striping and plating for over 100 cycles at a current density of 0.05 mA cm-2 . The film was effective in blocking solvent molecules and counterions from crossing over for extended period of time.

Highly Durable, Self-Standing Solid-State Supercapacitor Based on an Ionic Liquid-Rich Ionogel and Porous Carbon Nanofiber Electrodes.

A high-performance, self-standing solid-state supercapacitor is prepared by incorporating an ionic liquid (IL)-rich ionogel made with 95 wt % IL (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and 5 wt % methyl cellulose, a polymer matrix, into highly interconnected 3-D activated carbon nanofiber (CNF) electrodes. The ionogel exhibits strong mechanical properties with a storage modulus of 5 MPa and a high ionic conductivity of 5.7 mS cm-1 at 25 °C. The high-surface-area CNF-based electrode (2282 m2 g-1), obtained via an electrospinning technique, exhibits hierarchical porosity generated both in situ during pyrolysis and ex situ via KOH activation. The porous architecture of the CNF electrodes facilitates the facile percolation of the soft but mechanically durable ionogel film, thereby enabling intimate contact between porous nanofibers and the gel electrolyte interface. The supercapacitor demonstrates promising capacitive characteristics, including a gravimetric capacitance of 153 F g-1, a high specific energy density of 65 W h kg-1, and high cycling stability, with a capacitance fade of only 4% after 20 000 charge-discharge cycles at 1 A g-1. Moreover, device-level areal capacitances for the gel IL cell of 122 and 151 mF cm-2 are observed at electrode mass loadings of 3.20 and 5.10 mg cm-2, respectively.

A Self-Binding, Melt-Castable, Crystalline Organic Electrolyte for Sodium Ion Conduction.

The preparation and characterization of the cocrystalline solid-organic sodium ion electrolyte NaClO4 (DMF)3 (DMF=dimethylformamide) is described. The crystal structure of NaClO4 (DMF)3 reveals parallel channels of Na+ and ClO4- ions. Pressed pellets of microcrystalline NaClO4 (DMF)3 exhibit a conductivity of 3×10-4  S cm-1 at room temperature with a low activation barrier to conduction of 25 kJ mol-1 . SEM revealed thin liquid interfacial contacts between crystalline grains, which promote conductivity. The material melts gradually between 55-65 °C, but does not decompose, and upon cooling, it resolidifies as solid NaClO4 (DMF)3 , permitting melt casting of the electrolyte into thin films and the fabrication of cells in the liquid state and ensuring penetration of the electrolyte between the electrode active particles.

High-Density Recombinant Adeno-Associated Viral Particles are Competent Vectors for In Vivo Transduction.

Recombinant adeno-associated viral (rAAV) vectors have recently achieved clinical successes in human gene therapy. However, the commonly observed, heavier particles found in rAAV preparations have traditionally been ignored due to their reported low in vitro transduction efficiency. In this study, the biological properties of regular and high-density rAAV serotype 8 vectors, rAAVRD and rAAVHD, were systemically compared. Results demonstrated that both rAAVRD and rAAVHD exhibited similar DNA packaging profiles, while rAAVHD capsids contained fewer VP1 and VP2 proteins, indicating that the rAAVHD particles contained a higher DNA/protein ratio than that of rAAVRD particles. Dynamic light scattering and transmission electron microscopy data revealed that the diameter of rAAVHD was smaller than that of rAAVRD. In vitro, rAAVHD was two- to fourfold less efficient in transduction compared with rAAVRD. However, the transduction performance of rAAVHD and rAAVRD was similar in vivo. No significant difference in neutralizing antibody formation against rAAVRD and rAAVHD was observed, suggesting that the surface epitopes of rAAVRD and rAAVHD are congruent. In summary, the results of this study demonstrate that rAAVRD and rAAVHD are equally competent for in vivo transduction, despite their difference in vitro. Therefore, the use of rAAVHD vectors in human gene therapy should be further evaluated.

High Conductivity, High Strength Solid Electrolytes Formed by in Situ Encapsulation of Ionic Liquids in Nanofibrillar Methyl Cellulose Networks.

Strong, solid polymer electrolyte ion gels, with moduli in the MPa range, a capacitance of 2 µF/cm(2), and high ambient ionic conductivities (>1 × 10(-3) S/cm), all at room temperature, have been prepared from butyl-N-methyl pyrrolidinium bis(trifluoromethylsulfonyl) imide (PYR14TFSI) and methyl cellulose (MC). These properties are particularly attractive for supercapacitor applications. The ion gels are prepared by codissolution of PYR14TFSI and MC in N,N-dimethylformamide (DMF), which after heating and subsequent cooling form a gel. Evaporation of DMF leave thin, flexible, self-standing ion gels with up to 97 wt % PYR14TFSI, which have the highest combined moduli and ionic conductivity of ion gels to date, with an excellent electrochemical stability window (5.6 V). These favorable properties are attributed to the immiscibility of PYR14TFSI in MC, which permits the ionic conductivity to be independent of the MC at low MC content, and the in situ formation of a volume spanning network of semicrystalline MC nanofibers, which have a high glass transition temperature (Tg = 190 °C) and remain crystalline until they degrade at 300 °C.

Lamellar, micro-phase separated blends of methyl cellulose and dendritic polyethylene glycol, POSS-PEG.

Blends of methyl cellulose (MC) and liquid pegylated polyoctahedralsilsesquioxane (POSS-PEG) were prepared from non-gelled, aqueous solutions at room temperature (RT), which was below their gel temperatures (Tm). Lamellar, fibrillated films (pure MC) and increasingly micro-porous morphologies with increasing POSS-PEG content were formed, which had RT moduli between 1 and 5GPa. Evidence of distinct micro-phase separated MC and POSS-PEG domains was indicated by the persistence of the MC and POSS-PEG (at 77K) crystal structures in the X-ray diffraction data, and scanning transmission electron images. Mixing of MC and POSS-PEG in the interface region was indicated by suppression of crystallinity in the POSS-PEG, and increases/decreases in the glass transition temperatures (Tg) of POSS-PEG/MC in the blends compared with the pure components. These interface interactions may serve as cross-link sites between the micro-phase separated domains that permit incorporation of high amounts of POSS-PEG in the blends, prevent macro-phase separation and result in rubbery material properties (at high POSS-PEG content). Above Tg/Tm of POSS-PEG, the moduli of the blends increase with MC content as expected. However, below Tg/Tm of POSS-PEG, the moduli are greater for blends with high POSS-PEG content, suggesting that it behaves like semi-crystalline polyethylene oxide reinforced with silica (SiO1.5).

Nanoparticle-supported lipid bilayers as an in situ remediation strategy for hydrophobic organic contaminants in soils.

Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental organic contaminants due to their low water solubility and strong sorption onto organic/mineral surfaces. Here, nanoparticle-supported lipid bilayers (NP-SLBs) made of 100-nm SiO2 nanoparticles and the zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are investigated as constructs for removing PAHs from contaminated sites, using benzo[a]pyrene (BaP) as an example. DMPC in the form of small unilamellar vesicles (SUVs) or DMPC-NP-SLBs with excess DMPC-SUVs to support colloidal stability, when added to saturated BaP solutions, sorb BaP in ratios of up to 10/1 to 5/1 lipid/BaP, over a 2-week period at 33 °C. This rate increases with temperature. The presence of humic acid (HA), as an analog of soil organic matter, does not affect the BaP uptake rate by DMPC-NP-SLBs and DMPC-SUVs, indicating preferential BaP sorption into the hydrophobic lipids. HA increases the zeta potential of these nanosystems, but does not disrupt their morphology, and enhances their colloidal stability. Studies with the common soil bacteria Pseudomonas aeruginosa demonstrate viability and growth using DMPC-NP-SLBs and DMPC-SUVs, with and without BaP, as their sole carbon source. Thus, NP-SLBs may be an effective method for remediation of PAHs, where the lipids provide both the method of extraction and stability for transport to the contaminant site.

Effect of lamellarity and size on calorimetric phase transitions in single component phosphatidylcholine vesicles.

Nano-differential scanning calorimetry (nano-DSC) is a powerful tool in the investigation of unilamellar (small unilamellar, SUVs, or large unilamellar, LUVs) vesicles, as well as lipids on supported bilayers, since it measures the main gel-to-liquid phase transition temperature (Tm), enthalpies and entropies. In order to assign these transitions in single component systems, where Tm often occurred as a doublet, nano-DSC, dynamic light scattering and cryo-transmission electron microscopy (cryo-TEM) data were compared. The two Tms were not attributable to decoupled phase transitions between the two leaflets of the bilayer, i.e. nano-DSC measurements were not able to distinguish between the outer and inner leaflets of the vesicle bilayers. Instead, the two Tms were attributed to mixtures of oligolamellar and unilamellar vesicles, as confirmed by cryo-TEM images. Tm for the oligolamellar vesicles was assigned to the peak closest to that of the parent multilamellar vesicle (MLV) peak. The other transition was higher than that of the parent MLVs for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and increased in temperature as the vesicle size decreased, while it was lower in temperature than that of the parent MLVs for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and decreased as the vesicle size decreased. These subtle shifts arose due to small differences in the values of ΔH and ΔS, since Tm is determined by their ratio (ΔH/ΔS). It was not possible to completely eliminate oligolamellar structures for MLVs extruded with the 200 nm pore size filter, even after 120 passes, while these structures were eliminated for MLVs extruded through the 50 nm pore size filter.

Lipid exchange and transfer on nanoparticle supported lipid bilayers: effect of defects, ionic strength, and size.

Lipid exchange/transfer has been compared for zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-d54-sn-glycero-3-phosphocholine (DMPC) small unilamellar vesicles (SUVs) and for the same lipids on silica (SiO2) nanoparticle supported lipid bilayers (NP-SLBs) as a function of ionic strength, temperature, temperature cycling, and NP size, above the main gel-to-liquid crystal phase transition temperature, Tm, using d- and h-DMPC and DPPC. Increasing ionic strength decreases the exchange kinetics for the SUVs, but more so for the NP-SLBs, due to better packing of the lipids and increased attraction between the lipid and support. When the NP-SLBs (or SUVs) are cycled above and below Tm, the exchange rate increases compared with exchange at the same temperature without cycling, for similar total times, suggesting that defects provide sites for more facile removal and thus exchange of lipids. Defects can occur: (i) at the phase boundaries between coexisting gel and fluid phases at Tm; (ii) in bare regions of exposed SiO2 that form during NP-SLB formation due to mismatched surface areas of lipid and NPs; and (iii) during cycling as the result of changes in area of the lipids at Tm and mismatched thermal expansion coefficient between the lipids and SiO2 support. Exchange rates are faster for NP-SLBs prepared with the nominal amount of lipid required to form a NP-SLB compared with NP-SLBs that have been prepared with excess lipids to minimize SiO2 patches. Nanosystems prepared with equimolar mixtures of NP-SLBs composed of d-DMPC (d(DMPC)-NP-SLB) and SUVs composed of h-DMPC (h(DMPC)-SUV) show that the calorimetric transition of the "donor" h(DMPC)-SUV decreases in intensity without an initial shift in Tm, indicating that the "acceptor" d(DMPC)-NP-SLB can accommodate more lipids, through either further fusion or insertion of lipids into the distal monolayer. Exchange for d/h(DMPC)-NP-SLB is in the order 100 nm SiO2 > 45 nm SiO2 > 5 nm SiO2.

The polyoctahedral silsesquioxane (POSS) 1,3,5,7,9,11,13,15-octaphenylpentacyclo[9.5.1.1(3,9).1(5,15).1(7,13)]octasiloxane (octaphenyl-POSS).

Solvent-free single crystals of 1,3,5,7,9,11,13,15-octaphenylpentacyclo[9.5.1.1(3,9).1(5,15).1(7,13)]octasiloxane (abbreviated as octaphenyl-POSS), C48H40O12Si8, were obtained by dehydration/condensation of the tetrol Si4O4(Ph)4(OH)4. The powder pattern generated from the single-crystal data matches well with the experimentally measured powder pattern of commercial octaphenyl-POSS. The geometry of the centrosymmetric molecule in the crystal was compared with that in the gas phase, and had shorter Si-O bond lengths and a broader range of Si-O-Si bond angles. The average Si-O bond length [1.621 (3) Å], and Si-O-Si and O-Si-O bond angles [149 (5) and 109 (1)°, respectively] were within the same range measured previously for octaphenyl-POSS solvates.

Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties.

The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact on the plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential, and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viability assays, we identified the main physicochemical parameters of the lipid bilayers, liposomes, and lipoplexes that are affected by the gemini surfactant addition. We also correlated the cationic bilayer composition with the dynamics of the DNA compaction process and with transfection efficiency, cytotoxicity, and the internalization mechanism of the resultant nucleic acid complexes. We found that the blending of gemini surfactant into the cationic bilayers fluidized the supramolecular assemblies, reduced the amount of positive charge required to fully compact the plasmid DNA and, in certain cases, changed the internalization mechanism of the lipoplexes. The transfection efficiency of select ternary lipoplexes derived from cationic gemini surfactants and lipids was several times superior to the transfection efficiency of corresponding binary lipoplexes, also surpassing standard transfection systems. The overall impact of gemini surfactants into the formation and dynamic of cationic bilayers was found to depend heavily on the presence of colipids, their nature, and amount present in lipoplexes. The study confirmed the possibility of combining the specific properties of pyridinium gemini surfactants and cationic lipids synergistically to obtain efficient synthetic transfection systems with negligible cytotoxicity useful for therapeutic gene delivery.

Tuning the self-assembling of pyridinium cationic lipids for efficient gene delivery into neuronal cells.

We are reporting a new set of biocompatible, low-toxicity pyridinium cationic lipids based on a dopamine backbone on which hydrophobic alkyl tails are attached via an ether linkage. Due to their optimized hydrophilic/hydrophobic interface and packing parameter, the new lipids are able to strongly self-assemble either alone or when coformulated with colipids DOPE or cholesterol. The supra-molecular assemblies generated with the novel pyridinium amphiphiles were characterized in bulk and in solution via a combination of techniques including DSC, nanoDSC, SAXS, TOPM, TEM, DLS, zeta potential, and electrophoretic mobility measurements. These cationic bilayers can efficiently condense and deliver DNA to a large variety of cell lines, as proven by our self-assembling/physicochemical/biological correlation study. Using the luciferase reporter gene plasmid, we have also conducted a comprehensive structure-activity relationship study, which identified the best structural parameters and formulations for efficient and nontoxic gene delivery. Several formulations greatly surpassed established transfection systems with proved in vitro and in vivo efficiency, being able to transfect a large variety of malignant cells even in the presence of elevated levels of serum. The most efficient formulation was able to transfect selectively primary rat dopaminergic neurons harvested from nucleus accumbens, and neurons from the frontal cortex, a premise that recommends these synthetic vectors for future in vivo delivery studies for neuronal reprogramming.

Formation of lipid sheaths around nanoparticle-supported lipid bilayers.

High-surface-area nanoparticles often cluster, with unknown effects on their cellular uptake and environmental impact. In the presence of vesicles or cell membranes, lipid adsorption can occur on the nanoparticles, resulting in the formation of supported lipid bilayers (SLBs), which tend to resist cellular uptake. When the amount of lipid available is in excess compared with that required to form a single-SLB, large aggregates of SLBs enclosed by a close-fitting lipid bilayer sheath are shown to form. The proposed mechanism for this process is one where small unilamellar vesicles (SUVs) adsorb to aggregates of SLBs just above the gel-to-liquid phase transition temperature, T(m) , of the lipids (as observed by dynamic light scattering), and then fuse with each other (rather than to the underlying SLBs) upon cooling below T(m) . The sacks of SLB nanoparticles that are formed are encapsulated by the contiguous close-fitting lipid sheath, and precipitate below T(m) , due to reduced hydration repulsion and the absence of undulation/protrusion forces for the lipids attached to the solid support. The single-SLBs can be released above T(m) , where these forces are restored by the free lipid vesicles. This mechanism may be useful for encapsulation/release of drugs/DNA, and has implications for the toxic effects of nanoparticles, which may be mitigated by lipid sequestration.

Effect of curvature on nanoparticle supported lipid bilayers investigated by Raman spectroscopy.

The packing of lipids on silica (SiO(2)) nanoparticles (NPs) was investigated by Raman spectroscopy for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) as a function of their size, for SiO(2) NPs of 5, 15, 25, 45, and 100 nm nominal diameter. Raman spectral indicators in the C-C and C-H stretching regions were used to determine conformational order and alkyl chain packing for these systems. As the ratio of NP to lipid size decreases, packing in a normal bilayer configuration increases free volume and decreases hydrophobic interaction between the chains. For the 15, 25, 45, and 100 nm SiO(2), for which single supported lipid bilayers (SLBs) are formed around the NPs, the Raman data indicate that there is increased interdigitation and increased lateral packing order between the chains with decreasing NP size, which improves hydrophobic association and decreases the voids that would occur for normal bilayers. For the same size NP, there is increased interdigitation and lateral packing for the DSPC compared with DPPC lipids, as expected based on the greater void volume that would be created for the longer alkyl chain lengths. Another mechanism for filling this void space is the formation of gauche kinks for the terminal methyl groups at the center of the bilayer, which can be monitored by a Raman band at 1122 cm(-1). These gauche defects are most prevalent for the largest size (100 nm) NPs but are observed for all NP sizes. For the 5 nm SLBs, which form aggregates, we hypothesize that bilayer bridging can occur between the NPs. Compared with the 15 nm NPs, the order parameter increases but there are fewer trans conformers, possibly due to chains that are loosely packed or isolated in the interstitial regions.

Supported lipid bilayer nanosystems: stabilization by undulatory-protrusion forces and destabilization by lipid bridging.

Control of the stabilization/destabilization of supported lipid bilayers (SLBs) on nanoparticles is important for promotion of their organized assembly and for their use as delivery vehicles. At the same time, understanding the mechanism of these processes can yield insight into nanoparticle-cell interactions and nanoparticle toxicity. In this study, the suspension/precipitation process of zwitterionic lipid/SiO(2) nanosystems was analyzed as a function of ionic strength and as a function of the ratio of lipid/SiO(2) surface areas, at pH = 7.6. Salt is necessary to induce supported lipid bilayer (SLB) formation for zwitterionic lipids on silica (SiO(2)) (Seantier, B.; Kasemo, B., Influence of Mono- and Divalent Ions on the Formation of Supported Phospholipid Bilayers via Vesicle Adsorption. Langmuir 2009, 25 (10), 5767-5772). However, for zwitterionic SLBs on SiO(2) nanoparticles, addition of salt can cause precipitation of the SLBs, due to electrostatic shielding by both the lipid and the salt and to the suppression of thermal undulation/protrusion repulsive forces for lipids on solid surfaces. At ionic strengths that cause precipitation of SLBs, it was found that addition of excess SUVs, at ratios where there were equal populations of SUVs and SLBs, restored the undulation/protrusion repulsive forces and restabilized the suspensions. We suggest that SUVs separate SLBs in the suspension, as observed by TEM, and that SLB-SLB interactions are replaced by SLB-SUV interactions. Decreasing the relative amount of lipid, to the extent that there was less lipid available than the amount required for complete bilayer coverage of the SiO(2), resulted in precipitation of the nanosystem by a process of nanoparticle lipid bridging. For this case, we postulate a process in which lipid bilayer patches on one nanoparticle collide with bare silica patches on another SiO(2) nanoparticle, forming a single bilayer bridge between them. TEM data confirmed these findings, thus indicating that lipid bridges are composed of half bilayers on adjoining SiO(2) nanoparticles.

Stabilization of soft lipid colloids: competing effects of nanoparticle decoration and supported lipid bilayer formation.

Stabilization against fusion of zwitterionic lipid small unilamellar vesicles (SUVs) by charged nanoparticles is essential to prevent premature inactivation and cargo unloading. In the present work, we examined the stabilization of DMPC and DPPC SUVs by monolithic silica (SiO(2)) nanoparticle envelopment, for SiO(2) with 4-6, 10-20, 20-30, and 40-50 nm nominal diameter. We found that for these soft colloids stabilization is critically dependent on whether fusion occurs between the charged nanoparticles and neutral SUVs to form supported lipid bilayers (SLBs), or whether the reverse occurs, namely, nanoparticle decoration of the SUVs. While SLB formation is accompanied by precipitation, nanoparticle decoration results in long-term stabilization of the SUVs. The fate of the nanosystem depends on the size of the nanoparticles and on the ionic strength of the medium. We found that, in the case of highly charged SiO(2) nanoparticles in water, there is no SUV fusion to SiO(2) for a specific range of nanoparticle sizes. Instead, the negatively charged SiO(2) nanoparticles surround the uncharged SUVs, resulting in electrostatic repulsion between the decorated SUVs, thus preventing their aggregation and precipitation. Addition of millimolar amounts of NaCl results in rapid SLB formation and precipitation. This study has great potential impact toward better understanding the interaction of nanoparticles with biological membranes and the factors affecting their use as drug carriers or sensors.

Formation and colloidal stability of DMPC supported lipid bilayers on SiO2 nanobeads.

Supported lipid bilayers (SLBs) of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were formed on 20-100 nm silica (SiO(2)) nanobeads, and the formation was accompanied by an 8 nm increase in diameter of the SiO(2), consistent with single nanobeads surrounded by a DMPC bilayer. Complete SLBs were formed when the nominal surface areas of the DMPC matched that of the silica, SA(DMPC)/SA(SiO2) = 1, and required increasing ionic strength and time to form on smaller size nanobeads, as shown by a combination of nano-differential scanning calorimetry (nano-DSC), dynamic light scattering (DLS), and zeta potential (zeta) measurements. For 5 nm SiO(2), where the nanoparticle and DMPC dimensions were comparable, DMPC fused and formed SLBs on the nanobeads, but it did not form single bilayers around them. Instead, stable agglomerates of 150-1000 nm were formed over a wide surface ratio range (0.25 < or = SA(DMPC)/SA(SiO2) < 2) in 0.75 mM NaCl. At ionic strengths > 1 mM NaCl, charge shielding, as measured by zeta potential measurements (zeta --> 0), resulted in precipitation of the SLBs.