The Power of Three: Nanomaterials for Natural Killer (NK) Cell Immunoengineering Maximize Their Potency if They Exploit Multireceptor Stimulation.

Many emerging cancer treatments are immunotherapies that modulate Natural Killer- (NK) or T cell activation, posing a challenge to develop immunoengineering nanomaterials that improve on the performance of molecular reagents. In physiological activation, multiple immunoreceptors signal in consort; however, current biomaterials do not replicate this. Here, NK cells are created for the first time, activating bionanomaterials that stimulate >2 immunoreceptors.

Epithelial-stromal cell interactions and extracellular matrix mechanics drive the formation of airway-mimetic tubular morphology in lung organoids.

Complex human airway cellular organization where extracellular matrix (ECM) and epithelial and stromal lineages interact present challenges for organ study . Current lung models that focus on the lung epithelium do not represent complex airway morphology and cell-ECM interactions seen . Models including stromal populations often separate them via a semipermeable barrier precluding cell-cell interaction or the effect of ECM mechanics.

Micromechanical mapping of the intact ovary interior reveals contrasting mechanical roles for follicles and stroma.

Follicle development in the ovary must be tightly regulated to ensure cyclical release of oocytes (ovulation). Disruption of this process is a common cause of infertility, for example via polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Recent ex vivo studies suggest that follicle growth is mechanically regulated, however, crucially, the actual mechanical properties of the follicle microenvironment have remained unknown.

Enhancing Structural Properties and Performance of Graphene-Based Devices Using Self-Assembled HMDS Monolayers.

The performance of graphene devices is often limited by defects and impurities induced during device fabrication. Polymer residue left on the surface of graphene after photoresist processing can increase electron scattering and hinder electron transport. Furthermore, exposing graphene to plasma-based processing such as sputtering of metallization layers can increase the defect density in graphene and alter the device performance.

Carbon-Dot-Enhanced Graphene Field-Effect Transistors for Ultrasensitive Detection of Exosomes.

Graphene field-effect transistors (GFETs) are suitable building blocks for high-performance electrical biosensors, because graphene inherently exhibits a strong response to charged biomolecules on its surface. However, achieving ultralow limit-of-detection (LoD) is limited by sensor response time and screening effect. Herein, we demonstrate that the detection limit of GFET biosensors can be improved significantly by decorating the uncovered graphene sensor area with carbon dots (CDs).

Stabilizing gold nanoparticles for use in X-ray computed tomography imaging of soil systems.

This investigation establishes a system of gold nanoparticles that show good colloidal stability as an X-ray computed tomography (XCT) contrast agent under soil conditions. Gold nanoparticles offer numerous beneficial traits for experiments in biology including: comparatively minimal phytotoxicity, X-ray attenuation of the material and the capacity for functionalization. However, soil salinity, acidity and surface charges can induce aggregation and destabilize gold nanoparticles, hence in biomedical applications polymer coatings are commonly applied to gold nanoparticles to enhance stability in the environment.

Chemically Functionalised Graphene FET Biosensor for the Label-free Sensing of Exosomes.

A graphene field-effect transistor (gFET) was non-covalently functionalised with 1-pyrenebutyric acid N-hydroxysuccinimide ester and conjugated with anti-CD63 antibodies for the label-free detection of exosomes. Using a microfluidic channel, part of a graphene film was exposed to solution. The change in electrical properties of the exposed graphene created an additional minimum alongside the original Dirac point in the drain-source current (I) - back-gate voltage (V) curve.

L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles.

The blood-brain barrier (BBB) is a protective endothelial barrier lining the brain microvasculature which prevents brain delivery of therapies against brain diseases. Hence, there is an urgent need to develop vehicles which efficiently penetrate the BBB to deliver therapies into the brain. The drug L-DOPA efficiently and specifically crosses the BBB via the large neutral amino acid transporter (LAT)-1 protein to enter the brain.

Activation of Human Natural Killer Cells by Graphene Oxide-Templated Antibody Nanoclusters.

An emerging new paradigm is that immune cell activation is controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals that activate or desensitize NK cells are, however, individual molecules that do not replicate this nanoscale organization of proteins. Here, we use nanoscale graphene oxide (NGO) as a template to generate soluble nanoscale clusters of Natural Killer cell-activating antibodies.

Multibranched Gold Nanoparticles with Intrinsic LAT-1 Targeting Capabilities for Selective Photothermal Therapy of Breast Cancer.

Because of the critical role of the large neutral amino acid transporter-1 (LAT-1) in promoting tumor growth and proliferation, it is fast emerging as a highly attractive biomarker for the imaging and treatment of human malignancies, including breast cancer. While multibranched gold nanoparticles (AuNPs) have emerged as a promising modality in the photothermal therapy (PTT) of cancers, some of the key challenges limiting their clinical translation lie in the need to develop reproducible and cost-effective synthetic methods as well as the selective accumulation of sufficient AuNPs at tumor sites. In this study, we report a simple and direct seed-mediated synthesis of monodispersed multibranched AuNPs using the catechol-containing LAT-1 ligands, L- and D-dopa, to confer active cancer targeting.

Scalable High-Affinity Stabilization of Magnetic Iron Oxide Nanostructures by a Biocompatible Antifouling Homopolymer.

Iron oxide nanostructures have been widely developed for biomedical applications because of their magnetic properties and biocompatibility. In clinical applications, stabilization of these nanostructures against aggregation and nonspecific interactions is typically achieved using weakly anchored polysaccharides, with better-defined and more strongly anchored synthetic polymers not commercially adopted because of their complexity of synthesis and use. Here, we show for the first time stabilization and biocompatibilization of iron oxide nanoparticles by a synthetic homopolymer with strong surface anchoring and a history of clinical use in other applications, poly(2-methacryloyloxyethyl phosphorylcholine) [poly(MPC)].

T cell immunoengineering with advanced biomaterials.

Recent advances in biomaterials design offer the potential to actively control immune cell activation and behaviour. Many human diseases, such as infections, cancer, and autoimmune disorders, are partly mediated by inappropriate or insufficient activation of the immune system. T cells play a central role in the host immune response to these diseases, and so constitute a promising cell type for manipulation.

Mechanisms of Polymer-Templated Nanoparticle Synthesis: Contrasting ZnS and Au.

We combine solution small-angle X-ray scattering (SAXS) and high-resolution analytical transmission electron microscopy (ATEM) to gain a full mechanistic understanding of substructure formation in nanoparticles templated by block copolymer reverse micelles, specifically poly(styrene)-block-poly(2-vinylpyridine). We report a novel substructure for micelle-templated ZnS nanoparticles, in which small crystallites (∼4 nm) exist within a larger (∼20 nm) amorphous organic-inorganic hybrid matrix. The formation of this complex structure is explained via SAXS measurements that characterize in situ for the first time the intermediate state of the metal-loaded micelle core: Zn(2+) ions are distributed throughout the micelle core, which solidifies as a unit on sulfidation.

Modular and Versatile Spatial Functionalization of Tissue Engineering Scaffolds through Fiber-Initiated Controlled Radical Polymerization.

Native tissues are typically heterogeneous and hierarchically organized, and generating scaffolds that can mimic these properties is critical for tissue engineering applications. By uniquely combining controlled radical polymerization (CRP), end-functionalization of polymers, and advanced electrospinning techniques, a modular and versatile approach is introduced to generate scaffolds with spatially organized functionality. Poly-ε-caprolactone is end functionalized with either a polymerization-initiating group or a cell-binding peptide motif cyclic Arg-Gly-Asp-Ser (cRGDS), and are each sequentially electrospun to produce zonally discrete bilayers within a continuous fiber scaffold.

Cytotoxicity and intracellular dissolution of nickel nanowires.

The assessment of cytotoxicity of nanostructures is a fundamental step for their development as biomedical tools. As widely used nanostructures, nickel nanowires (Ni NWs) seem promising candidates for such applications. In this work, Ni NWs were synthesized and then characterized using vibrating sample magnetometry, energy dispersive X-Ray analysis, and electron microscopy.

Nanoscale ligand spacing influences receptor triggering in T cells and NK cells.

Bioactive nanoscale arrays were constructed to ligate activating cell surface receptors on T cells (the CD3 component of the TCR complex) and natural killer (NK) cells (CD16). These arrays are formed from biofunctionalized gold nanospheres with controlled interparticle spacing in the range 25-104 nm. Responses to these nanoarrays were assessed using the extent of membrane-localized phosphotyrosine in T cells stimulated with CD3-binding nanoarrays and the size of cell contact area for NK cells stimulated with CD16-binding nanoarrays.

The stability of silver nanoparticles in a model of pulmonary surfactant.

The growing use of silver nanoparticles (AgNPs) in consumer products has raised concerns about their potential impact on the environment and human health. Whether AgNPs dissolve and release Ag(+) ions, or coarsen to form large aggregates, is critical in determining their potential toxicity. In this work, the stability of AgNPs in dipalmitoylphosphatidylcholine (DPPC), the major component of pulmonary surfactant, was investigated as a function of pH.

Regulation of integrin adhesions by varying the density of substrate-bound epidermal growth factor.

Substrates coated with specific bioactive ligands are important for tissue engineering, enabling the local presentation of extracellular stimulants at controlled positions and densities. In this study, we examined the cross-talk between integrin and epidermal growth factor (EGF) receptors following their interaction with surface-immobilized Arg-Gly-Asp (RGD) and EGF ligands, respectively. Surfaces of glass coverslips, modified with biotinylated silane-polyethylene glycol, were functionalized by either biotinylated RGD or EGF (or both) via the biotin-NeutrAvidin interaction.

Structure and collapse of a surface-grown strong polyelectrolyte brush on sapphire.

We have used neutron reflectometry to investigate the behavior of a strong polyelectrolyte brush on a sapphire substrate, grown by atom-transfer radical polymerization (ATRP) from a silane-anchored initiator layer. The initiator layer was deposited from vapor, following treatment of the substrate with an Ar/H(2)O plasma to improve surface reactivity. The deposition process was characterized using X-ray reflectometry, indicating the formation of a complete, cross-linked layer.

Direct measurement of normal and shear forces between surface-grown polyelectrolyte layers.

This paper presents measurements, using the surface force balance (SFB), of the normal and shear forces in aqueous solutions between polyelectrolyte layers grown directly on mica substrates (grafted-from). The grafting-from was via surface-initiated atom transfer radical polymerization (surface-initiated ATRP) using a positively charged methacrylate monomer. X-ray reflectometry measurements confirm the successful formation of polyelectrolyte layers by this method.

Titanium-silicon oxide film structures for polarization-modulated infrared reflection absorption spectroscopy.

We present a titanium-silicon oxide film structure that permits polarization modulated infrared reflection absorption spectroscopy on silicon oxide surfaces. The structure consists of a ~6 nm sputtered silicon oxide film on a ~200 nm sputtered titanium film. Characterization using conventional and scanning transmission electron microscopy, electron energy loss spectroscopy, X-ray photoelectron spectroscopy and X-ray reflectometry is presented.

Applying grazing incidence X-ray reflectometry (XRR) to characterising nanofilms on mica.

Molecularly smooth mica has hitherto not been widely used as a substrate for the X-ray reflectometry (XRR) technique. That is largely due to the difficulty of achieving flatness over a sufficiently large area of mica. Here we show that this difficulty can be overcome by slightly bending the mica substrate over an underlying cylinder; the enhanced rigidity of the bent mica sheet along the axis of the cylinder provides sufficient flatness along this axis for XRR measurements.

The formation of spherulites by amyloid fibrils of bovine insulin.

Bovine insulin has long been known to self-assemble in vitro into amyloid fibrils. We have observed a further higher-order self-association of the protein into spherical structures, with diameters typically around 50 microm but ranging from 10 to 150 microm. In a polarizing light microscope, these structures exhibit a "Maltese-cross" extinction pattern typical of spherulites.