Imperial College London

Professor David W. McComb

Faculty of EngineeringDepartment of Materials

Adjunct Professor
 
 
 
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Contact

 

+44 (0)20 7594 6750d.mccomb Website

 
 
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Location

 

Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

322 results found

Sternlicht H, McComb DW, Padture NP, 2022, Interaction of ytterbium pyrosilicate environmental-barrier-coating ceramics with molten calcia-magnesia-aluminosilicate glass: Part II, Interfaces, Acta Materialia, Vol: 241, ISSN: 1359-6454

Interfaces in as-processed β-Yb2Si2O7 environmental barrier coating (EBC) ceramics, and those after high-temperature (1500 °C) interaction with a calcia-magnesia-aluminosilicate (CMAS) glass from Part I are studied in further detail using high-resolution transmission electron microscopy (HRTEM), annular dark field scanning TEM (ADF STEM) and high-angle ADF (HAADF) STEM. Disconnections are detected, or inferred, at twin and general grain-boundaries and also at phase boundaries. Grain-boundary and facet planes are found to be aligned parallel to {110} planes of β-Yb2Si2O7. When detected, step planes are also found to be aligned parallel to β-Yb2Si2O7 {110} planes. At the same time, the dislocation component has major projections aligned parallel to {110} planes of β-Yb2Si2O7. As such, both the step and the dislocation components of the disconnections are anisotropic. The tendency of the grain-boundary and facet planes at interfaces in the system to align parallel to β-Yb2Si2O7{110} planes, both before and after CMAS-interaction, is discussed. The chemistry of grain-boundaries in the vicinity of the disconnections is found to be non-stoichiometric, but this by itself cannot account for the extended contrast variations along twin boundaries. Thus, contrast variations along grain boundaries are associated mainly with the presence of disconnections and associated strain, as well as long-range distortions in the unit cells in twin boundaries. These anisotropic disconnections are associated with the mechanisms of grain-boundary and phase-boundary migration, and thus, they have implications on the evolution of microstructures in this system. Combined insights from Part I and this Part II elucidate the nature of the interfaces in β-Yb2Si2O7 EBC ceramic and the mechanisms of CMAS glass penetration.

Journal article

Yan J, Zhang Y, Du S, Hou X, Li W, Zeng C, Zhang C, Cheng J, Deng B, McComb DW, Zhao W, Xue Y, Kang DD, Cheng X, Dong Yet al., 2022, Nanomaterials-Mediated Co-Stimulation of Toll-Like Receptors and CD40 for Antitumor Immunity, Advanced Materials, Vol: 34, ISSN: 0935-9648

Toll-like receptors (TLRs) and CD40-related signaling pathways represent critical bridges between innate and adaptive immune responses. Here, an immunotherapy regimen that enables co-stimulation of TLR7/8- and CD40-mediated pathways is developed. TLR7/8 agonist resiquimod (R848) derived amino lipids, RAL1 and RAL2, are synthesized and formulated into RAL-derived lipid nanoparticles (RAL-LNPs). The RAL2-LNPs show efficient CD40 mRNA delivery to DCs both in vitro (90.8 ± 2.7%) and in vivo (61.3 ± 16.4%). When combined with agonistic anti-CD40 antibody, this approach can produce effective antitumor activities in mouse melanoma tumor models, thereby suppressing tumor growth, prolonging mouse survival, and establishing antitumor memory immunity. Overall, RAL2-LNPs provide a novel platform toward cancer immunotherapy by integrating innate and adaptive immunity.

Journal article

Pavlović RZ, Zhiquan L, Finnegan TJ, Waudby CA, Wang X, Gunawardana VWL, Zhu X, Wong CM, Hamby T, Moore CE, Hoefer N, McComb DW, Sevov CS, Badjić JDet al., 2022, Closed Aromatic Tubes-Capsularenes., Angew Chem Int Ed Engl, Vol: 61

In this study, we describe a synthetic method for incorporating arenes into closed tubes that we name capsularenes. First, we prepared vase-shaped molecular baskets 4-7. The baskets comprise a benzene base fused to three bicycle[2.2.1]heptane rings that extend into phthalimide (4), naphthalimide (6), and anthraceneimide sides (7), each carrying a dimethoxyethane acetal group. In the presence of catalytic trifluoroacetic acid (TFA), the acetals at top of 4, 6 and 7 change into aliphatic aldehydes followed by their intramolecular cyclization into 1,3,5-trioxane (1 H NMR spectroscopy). Such ring closure is nearly a quantitative process that furnishes differently sized capsularenes 1 (0.7×0.9 nm), 8 (0.7×1.1 nm;) and 9 (0.7×1.4 nm;) characterized by X-Ray crystallography, microcrystal electron diffraction, UV/Vis, fluorescence, cyclic voltammetry, and thermogravimetry. With exceptional rigidity, unique topology, great thermal stability, and perhaps tuneable optoelectronic characteristics, capsularenes hold promise for the construction of novel organic electronic devices.

Journal article

Ma D, Deng B, Sun C, McComb DW, Gu Cet al., 2022, The Mechanical Microenvironment Regulates Axon Diameters Visualized by Cryo-Electron Tomography., Cells, Vol: 11

Axonal varicosities or swellings are enlarged structures along axon shafts and profoundly affect action potential propagation and synaptic transmission. These structures, which are defined by morphology, are highly heterogeneous and often investigated concerning their roles in neuropathology, but why they are present in the normal brain remains unknown. Combining confocal microscopy and cryo-electron tomography (Cryo-ET) with in vivo and in vitro systems, we report that non-uniform mechanical interactions with the microenvironment can lead to 10-fold diameter differences within an axon of the central nervous system (CNS). In the brains of adult Thy1-YFP transgenic mice, individual axons in the cortex displayed significantly higher diameter variation than those in the corpus callosum. When being cultured on lacey carbon film-coated electron microscopy (EM) grids, CNS axons formed varicosities exclusively in holes and without microtubule (MT) breakage, and they contained mitochondria, multivesicular bodies (MVBs), and/or vesicles, similar to the axonal varicosities induced by mild fluid puffing. Moreover, enlarged axon branch points often contain MT free ends leading to the minor branch. When the axons were fasciculated by mimicking in vivo axonal bundles, their varicosity levels reduced. Taken together, our results have revealed the extrinsic regulation of the three-dimensional ultrastructures of central axons by the mechanical microenvironment under physiological conditions.

Journal article

Trout AH, Kurfman SW, Shi Y, Chilcote M, Flatté ME, Johnston-Halperin E, McComb DWet al., 2022, Probing the structure of vanadium tetracyanoethylene using electron energy-loss spectroscopy, APL Materials, Vol: 10

The molecule-based ferrimagnetic semiconductor vanadium tetracyanoethylene (V[TCNE]x, x ≈ 2) has garnered interest from the quantum information community due to its excellent coherent magnonic properties and ease of on-chip integration. Despite these attractive properties, a detailed understanding of the electronic structure and mechanism for long-range magnetic ordering have remained elusive due to a lack of detailed atomic and electronic structural information. Previous studies via x-ray absorption near edge spectroscopy and the extended x-ray absorption fine structure have led to various proposed structures, and in general, V[TCNE]x is believed to be a three-dimensional network of octahedrally coordinated V2+, each bonded to six TCNE molecules. Here, we elucidate the electronic structure, structural ordering, and degradation pathways of V[TCNE]x films by correlating calculations of density functional theory (DFT) with scanning transmission electron microscopy and electron energy-loss spectroscopy (EELS) of V[TCNE]x films. Low-loss EELS measurements reveal a bandgap and an excited state structure that agree quantitatively with DFT modeling, including an energy splitting between apical and equatorial TCNE ligands within the structure, providing experimental results directly backed by theoretical descriptions of the electronic structure driving the robust magnetic ordering in these films. Core-loss EELS confirms the presence of octahedrally coordinated V+2 atoms. Upon oxidation, changes in the C1s-π∗ peak indicate that C=C of TCNE is preferentially attacked. Furthermore, we identify a relaxation of the structural ordering as the films age. These results lay the foundation for a more comprehensive and fundamental understanding of magnetic ordering and dynamics in these classes of metal-ligand compounds.

Journal article

Hsu YH, Trout A, Bartlett JD, Smith CE, McComb DWet al., 2022, MMP20-Ablated Induced Aberrant Mineralization in Early Secretory Enamel, Microscopy and Microanalysis, Vol: 28, Pages: 1356-1358, ISSN: 1431-9276

Journal article

Hassan A, Kennedy WJ, Koerner H, Hwang J, McComb DWet al., 2022, Probing Changes in the Electronic Structure and Chemical Bonding of Ti<inf>3</inf>C<inf>2</inf>MXene Sheets with Electron Energy-Loss Spectroscopy, Microscopy and Microanalysis, Vol: 28, Pages: 1750-1751, ISSN: 1431-9276

Journal article

Cheng S, Wang B, Lyalin I, Bagués N, Bishop AJ, McComb DW, Kawakami RKet al., 2022, Atomic layer epitaxy of kagome magnet Fe<inf>3</inf>Sn<inf>2</inf>and Sn-modulated heterostructures, APL Materials, Vol: 10

Magnetic materials with kagome crystal structure exhibit rich physics, such as frustrated magnetism, skyrmion formation, topological flat bands, and Dirac/Weyl points. Until recently, most studies on kagome magnets have been performed on bulk crystals or polycrystalline films. Here, we report the atomic layer molecular beam epitaxy synthesis of high-quality thin films of topological kagome magnet Fe3Sn2. The structural and magnetic characterization of Fe3Sn2 on epitaxial Pt(111) identifies highly ordered films with c-plane orientation and an in-plane magnetic easy axis. Studies on the local magnetic structure by anomalous Nernst effect imaging reveal in-plane oriented micrometer size domains. Superlattice structures consisting of Fe3Sn2 and Fe3Sn are also synthesized by atomic layer molecular beam epitaxy, demonstrating the ability to modulate the sample structure at the atomic level. The realization of high-quality films by atomic layer molecular beam epitaxy opens the door to explore the rich physics of this system and investigate novel spintronic phenomena by interfacing Fe3Sn2 with other materials.

Journal article

Liu J-Q, Zhang C, Zhang X, Yan J, Zeng C, Talebian F, Lynch K, Zhao W, Hou X, Du S, Kang DD, Deng B, McComb DW, Bai X-F, Dong Yet al., 2022, Intratumoral delivery of IL-12 and IL-27 mRNA using lipid nanoparticles for cancer immunotherapy., J Control Release, Vol: 345, Pages: 306-313

Cytokines are important immunotherapeutics with approved drugs for the treatment of human cancers. However, systemic administration of cytokines often fails to achieve adequate concentrations to immune cells in tumors due to dose-limiting toxicity. Thus, developing localized therapy that directly delivers immune-stimulatory cytokines to tumors may improve the therapeutic efficacy. In this study, we generated novel lipid nanoparticles (LNPs) encapsulated with mRNAs encoding cytokines including IL-12, IL-27 and GM-CSF, and tested their anti-tumor activity. We first synthesized ionizable lipid materials containing di-amino groups with various head groups (DALs). The novel DAL4-LNP effectively delivered different mRNAs in vitro to tumor cells and in vivo to tumors. Intratumoral injection of DAL4-LNP loaded with IL-12 mRNA was most potent in inhibiting B16F10 melanoma tumor growth compared to IL-27 or GM-CSF mRNAs in monotherapy. Furthermore, intratumoral injection of dual DAL4-LNP-IL-12 mRNA and IL-27 mRNA showed a synergistic effect in suppressing tumor growth without causing systematic toxicity. Most importantly, intratumoral delivery of IL-12 and IL-27 mRNAs induced robust infiltration of immune effector cells, including IFN-γ and TNF-α producing NK and CD8+ T cells into tumors. Thus, intratumoral administration of DAL-LNP loaded with IL-12 and IL-27 mRNA provides a new treatment strategy for cancer.

Journal article

Ortega-Pineda L, Sunyecz A, Salazar-Puerta AI, Rincon-Benavides MA, Alzate-Correa D, Anaparthi AL, Guilfoyle E, Mezache L, Struckman HL, Duarte-Sanmiguel S, Deng B, McComb DW, Dodd DJ, Lawrence WR, Moore J, Zhang J, Reátegui E, Veeraraghavan R, Nelson MT, Gallego-Perez D, Higuita-Castro Net al., 2022, Designer Extracellular Vesicles Modulate Pro-Neuronal Cell Responses and Improve Intracranial Retention., Adv Healthc Mater, Vol: 11

Gene/oligonucleotide therapies have emerged as a promising strategy for the treatment of different neurological conditions. However, current methodologies for the delivery of neurogenic/neurotrophic cargo to brain and nerve tissue are fraught with caveats, including reliance on viral vectors, potential toxicity, and immune/inflammatory responses. Moreover, delivery to the central nervous system is further compounded by the low permeability of the blood brain barrier. Extracellular vesicles (EVs) have emerged as promising delivery vehicles for neurogenic/neurotrophic therapies, overcoming many of the limitations mentioned above. However, the manufacturing processes used for therapeutic EVs remain poorly understood. Here, we conducted a detailed study of the manufacturing process of neurogenic EVs by characterizing the nature of cargo and surface decoration, as well as the transfer dynamics across donor cells, EVs, and recipient cells. Neurogenic EVs loaded with Ascl1, Brn2, and Myt1l (ABM) are found to show enhanced neuron-specific tropism, modulate electrophysiological activity in neuronal cultures, and drive pro-neurogenic conversions/reprogramming. Moreover, murine studies demonstrate that surface decoration with glutamate receptors appears to mediate enhanced EV delivery to the brain. Altogether, the results indicate that ABM-loaded designer EVs can be a promising platform nanotechnology to drive pro-neuronal responses, and that surface functionalization with glutamate receptors can facilitate the deployment of EVs to the brain.

Journal article

Liu Q, Hoefer N, Berkbigler G, Cui Z, Liu T, Co AC, McComb DW, Wade CRet al., 2022, Strong CO<inf>2</inf>Chemisorption in a Metal-Organic Framework with Proximate Zn-OH Groups, Inorganic Chemistry, ISSN: 0020-1669

A novel Zn benzotriazolate metal-organic framework (MOF), [Zn9(OAc)6(bbtm)6] (1, bbtm2- = bis(benzotriazolyl)methanone, OAc- = acetate), has been synthesized and structurally characterized using micro-crystal electron diffraction. The framework contains 12-connected nonanuclear Zn clusters with Zn-OAc groups separated by short intercluster Zn···Zn distances of 6.06 Å. Postsynthetic OAc-/OH- ligand exchange followed by thermal activation generates 1a-OH, which adsorbs CO2 at very low pressures (1.37 mmol/g at 2.5 mbar) and requires an unusually high desorption temperature (>160 °C). Diffuse reflectance IR Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations have been used to interrogate the CO2 binding mechanism in 1a-OH. The formation of unsymmetric bridging carbonate ligands within the Zn···Zn pockets accompanied by strong hydrogen bonding of the carbonate with a neighboring zinc aqua ligand explains the remarkably strong CO2 affinity of 1a-OH.

Journal article

Wang B, Bagués N, Liu T, Kawakami RK, McComb DWet al., 2022, Extracting weak magnetic contrast from complex background contrast in plan-view FeGe thin films., Ultramicroscopy, Vol: 232

The desire to design and build skyrmion-based devices has led to the need to characterize magnetic textures in thin films of functional materials. This can usually be achieved through the Lorentz transmission electron microscopy (LTEM) and the Lorentz scanning transmission electron microscopy (LSTEM) in thin film cross-section and single crystal specimens. However, direct imaging of the magnetic texture in plan-view samples of thin (< 50 nm) films has proved to be challenging due to the complex "background" contrast associated with the microstructure and defects, as well as contributions from bending of the specimens. Using a mechanically polished 35 nm plan-view FeGe thin film, we have explored three methods to extract magnetic contrast from the complex background contrast observed; (1) background subtraction in defocused LTEM images, (2) frequency filtered CoM-DPC reconstructed from LSTEM datasets and 3) registration of 4D-STEM datasets acquired at different tilt angles. Using these methods, we have successfully implemented real space imaging of both the helical phase and skyrmion phase. The ability to understand nanoscale magnetic behavior from plan-view thin films is a fundamental step towards development of highly integrated spin electronics.

Journal article

Li W, Zhang X, Zhang C, Yan J, Hou X, Du S, Zeng C, Zhao W, Deng B, McComb DW, Zhang Y, Kang DD, Li J, Carson WE, Dong Yet al., 2021, Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy., Nat Commun, Vol: 12

Antibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.

Journal article

Zhao W, Zeng C, Yan J, Du S, Hou X, Zhang C, Li W, Deng B, McComb DW, Xue Y, Kang DD, Dong Yet al., 2021, Construction of Messenger RNA (mRNA) Probes Delivered By Lipid Nanoparticles to Visualize Intracellular Protein Expression and Localization at Organelles., Adv Mater, Vol: 33

Organelles are specialized compartments, where various proteins reside and play crucial roles to maintain essential cellular structures and functions in mammalian cells. A comprehensive understanding of protein expressions and subsequent localizations at each organelle is of great benefit to the development of organelle-based therapies. Herein, a set of single or dual organelle labeling messenger RNAs (SOLAR or DOLAR) is designed as novel imaging probes, which encode fluorescent proteins with various organelle localization signals. These mRNA probes enable to visualize the protein localizations at different organelles and investigate their trafficking from ribosomal machinery to specific organelles. According to the in vitro results, SOLAR probes show organelle targeting capabilities consistent with the design. Moreover, DOLAR probes with different linkers display distinct targeting properties depending on different organelle localization signals. Additionally, these mRNA probes also exhibit organelle labeling ability in vivo when delivered by lipid nanoparticles (LNPs). Therefore, these mRNA-based probes provide a unique tool to study cell organelles and may facilitate the design of organelle-based therapies.

Journal article

Wang B, Wu P-K, Bagués Salguero N, Zheng Q, Yan J, Randeria M, McComb DWet al., 2021, Stimulated Nucleation of Skyrmions in a Centrosymmetric Magnet., ACS Nano, Vol: 15, Pages: 13495-13503

Understanding the dynamics of skyrmion nucleation and manipulation is important for applications in spintronic devices. In this contribution, the spin textures at magnetic domain-boundaries stimulated by application of in-plane magnetic fields in a centrosymmetric kagome ferromagnet, Fe3Sn2, with thickness gradient are investigated using Lorentz transmission electron microscopy. Switching of the in-plane magnetic field is shown to induce a reversible transformation from magnetic stripes to skyrmions, or vice versa, at the interface between differently oriented domains. Micromagnetic simulations combined with experiments reveal that the rotatable anisotropy and thickness dependence of the response to the external in-plane field are the critical factors for the skyrmion formation. In addition, it is shown that the helicity of skyrmions can also be controlled using this dynamic process. The results suggest that magnetic materials with rotatable anisotropy are potential skyrmionic systems and provides a different approach for nucleation and manipulation of skyrmions in spintronic devices.

Journal article

Liu Y, Lee Y-U, Yi T, Wu K, Bouchet-Marquis C, Chan H, Breuer CK, McComb DWet al., 2021, Surgery and Sample Processing for Correlative Imaging of the Murine Pulmonary Valve., J Vis Exp

The underlying causes of heart valve related-disease (HVD) are elusive. Murine animal models provide an excellent tool for studying HVD, however, the surgical and instrumental expertise required to accurately quantify the structure and organization across multiple length scales have stunted its advancement. This work provides a detailed description of the murine dissection, en bloc staining, sample processing, and correlative imaging procedures for depicting the heart valve at different length scales. Hydrostatic transvalvular pressure was used to control the temporal heterogeneity by chemically fixing the heart valve conformation. Micro-computed tomography (µCT) was used to confirm the geometry of the heart valve and provide a reference for the downstream sample processing needed for the serial block face scanning electron microscopy (SBF-SEM). High-resolution serial SEM images of the extracellular matrix (ECM) were taken and reconstructed to provide a local 3D representation of its organization. µCT and SBF-SEM imaging methods were then correlated to overcome the spatial variation across the pulmonary valve. Though the work presented is exclusively on the pulmonary valve, this methodology could be adopted for describing the hierarchical organization in biological systems and is pivotal for the structural characterization across multiple length scales.

Journal article

Trout AH, Hodge KL, Scudder M, Goldberger JE, McComb DWet al., 2021, Low-Pressure Induced Disproportionation of Barium Distannide, Journal of Physical Chemistry C, Vol: 125, Pages: 15496-15502, ISSN: 1932-7447

Barium distannide (BaSn2), a potential precursor for stannene, is predicted to be a topological insulator. However, little is known about BaSn2 as the material is extremely air-sensitive. Here we present, for the first time, characterization of BaSn2 by scanning/transmission electron microscopy. We use advanced imaging and spectroscopy techniques to show disproportionation of BaSn2 particles into β-Sn + BaxSny. X-ray diffraction analysis confirms that this disproportionation is driven by exposure to a low-pressure environment.

Journal article

Liu Y, Feng X, Liu H, McComb DW, Breuer CK, Sacks MSet al., 2021, On the shape and structure of the murine pulmonary heart valve., Sci Rep, Vol: 11

Murine animal models are an established standard in translational research and provides a potential platform for studying heart valve disease. To date, studies on heart valve disease using murine models have been hindered by a lack of appropriate methodologies due to their small scale. In the present study, we developed a multi-scale, imaging-based approach to extract the functional structure and geometry for the murine heart valve. We chose the pulmonary valve (PV) to study, due to its importance in congenital heart valve disease. Excised pulmonary outflow tracts from eleven 1-year old C57BL/6J mice were fixed at 10, 20, and 30 mmHg to simulate physiological loading. Micro-computed tomography was used to reconstruct the 3D organ-level PV geometry, which was then spatially correlated with serial en-face scanning electron microscopy imaging to quantify local collagen fiber distributions. From the acquired volume renderings, we obtained the geometric descriptors of the murine PV under increasing transvalvular pressures, which demonstrated remarkable consistency. Results to date suggest that the preferred collagen orientation was predominantly in the circumferential direction, as in larger mammalian valves. The present study represents a first step in establishing organ-level murine models for the study of heart valve disease.

Journal article

Bartlett JD, Smith CE, Hu Y, Ikeda A, Strauss M, Liang T, Hsu Y-H, Trout AH, McComb DW, Freeman RC, Simmer JP, Hu JC-Cet al., 2021, MMP20-generated amelogenin cleavage products prevent formation of fan-shaped enamel malformations., Sci Rep, Vol: 11

Dental enamel forms extracellularly as thin ribbons of amorphous calcium phosphate (ACP) that initiate on dentin mineral in close proximity to the ameloblast distal membrane. Secreted proteins are critical for this process. Enam-/- and Ambn-/- mice fail to form enamel. We characterize enamel ribbon formation in wild-type (WT), Amelx-/- and Mmp20-/- mouse mandibular incisors using focused ion beam scanning electron microscopy (FIB-SEM) in inverted backscatter mode. In Amelx-/- mice, initial enamel mineral ribbons extending from dentin are similar in form to those of WT mice. As early enamel development progresses, the Amelx-/- mineral ribbons develop multiple branches, resembling the staves of a Japanese fan. These striking fan-shaped structures cease growing after attaining ~ 20 µm of enamel thickness (WT is ~ 120 µm). The initial enamel mineral ribbons in Mmp20-/- mice, like those of the Amelx-/- and WT, extend from the dentin surface to the ameloblast membrane, but appear to be fewer in number and coated on their sides with organic material. Remarkably, Mmp20-/- mineral ribbons also form fan-like structures that extend to ~ 20 µm from the dentin surface. However, these fans are subsequently capped with a hard, disorganized outer mineral layer. Amelogenin cleavage products are the only matrix components absent in both Amelx-/- and Mmp20-/- mice. We conclude that MMP20 and amelogenin are not critical for enamel mineral ribbon initiation, orientation, or initial shape. The pathological fan-like plates in these mice may form from the lack of amelogenin cleavage products, which appear necessary to form ordered hydroxyapatite.

Journal article

Hettiaratchy EC, Jamison JS, Wang B, Bagués N, Guest RA, Mccomb DW, Myers RCet al., 2020, Interface-induced ferromagnetism in μ-Fe<inf>2</inf>O<inf>3</inf>/β-Ga<inf>2</inf>O<inf>3</inf>superlattices, Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films, Vol: 38, ISSN: 0734-2101

Superlattices of antiferromagnetic μ-Fe2O3 and diamagnetic β-Ga2O3 are grown by plasma-assisted molecular beam epitaxy on (010) oriented β-Ga2O3 substrates in which ferromagnetism emerges above room temperature. To investigate the suspected interface origin of the ferromagnetic phase, identical superlattice structures are grown at various substrate temperatures and beam fluxes. Atomic-resolution scanning transmission electron microscopy images confirm the registry of μ-Fe2O3 to the β-Ga2O3 layers in these superlattices. Atomic force microscopy and high-resolution x-ray diffraction are used to examine the growth morphology and characterize the superlattice interface roughness. The saturation magnetization of the ferromagnetic phase is observed to increase strongly with the interface roughness. Conversely, smoother superlattices exhibit a weaker ferromagnetic response and a higher density of paramagnetic moments along with evidence of superparamagnetic clusters. These findings are consistent with the interface origin for the ferromagnetic response in these superlattices. The demonstration of an interface magnetic phase in nearly lattice-matched monoclinic Fe2O3/Ga2O3 opens the door to ultrawide bandgap heterostructure-engineered magnetoelectronic devices, where ferromagnetic switching of the interface phase can be incorporated into high-field devices.

Journal article

Zhang X, Zhao W, Nguyen GN, Zhang C, Zeng C, Yan J, Du S, Hou X, Li W, Jiang J, Deng B, McComb DW, Dorkin R, Shah A, Barrera L, Gregoire F, Singh M, Chen D, Sabatino DE, Dong Yet al., 2020, Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing., Sci Adv, Vol: 6

Messenger RNA (mRNA) therapeutics have been explored to treat various genetic disorders. Lipid-derived nanomaterials are currently one of the most promising biomaterials that mediate effective mRNA delivery. However, efficiency and safety of this nanomaterial-based mRNA delivery remains a challenge for clinical applications. Here, we constructed a series of lipid-like nanomaterials (LLNs), named functionalized TT derivatives (FTT), for mRNA-based therapeutic applications in vivo. After screenings on the materials, we identified FTT5 as a lead material for efficient delivery of long mRNAs, such as human factor VIII (hFVIII) mRNA (~4.5 kb) for expression of hFVIII protein in hemophilia A mice. Moreover, FTT5 LLNs demonstrated high percentage of base editing on PCSK9 in vivo at a low dose of base editor mRNA (~5.5 kb) and single guide RNA. Consequently, FTT nanomaterials merit further development for mRNA-based therapy.

Journal article

Hou X, Zhang X, Zhao W, Zeng C, Deng B, McComb DW, Du S, Zhang C, Li W, Dong Yet al., 2020, Author Correction: Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis., Nat Nanotechnol, Vol: 15

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Journal article

Lee AJ, Guo S, Flores J, Wang B, Bagués N, McComb DW, Yang Fet al., 2020, Investigation of the Role of Rare-Earth Elements in Spin-Hall Topological Hall Effect in Pt/Ferrimagnetic-Garnet Bilayers., Nano Lett, Vol: 20, Pages: 4667-4672

Topological magnetic textures such as skyrmions are being extensively studied for their potential application in spintronic devices. Recently, low-damping ferrimagnetic insulators (FMI) such as Tm3Fe5O12 have attracted significant interest as potential candidates for hosting skyrmions. Here, we report the detection of the spin-Hall topological Hall effect (SH-THE) in Pt/Tm3Fe5O12 and Pt/Y3Fe5O12 bilayers grown on various orientations of Gd3Ga5O12 substrates as well as on epitaxial buffer layers of Y3Sc2Al3O12, which separates the FMI from the substrate without sacrificing the crystal quality. The presence of SH-THE in all of the bilayers and trilayers provides evidence that rare-earth ions in either the FMI or substrate may not be critical for inducing an interfacial Dzyaloshinskii-Moriya interaction that is necessary to stabilize magnetic textures. Additionally, the use of substrates with various crystal orientations alters the magnetic anisotropy, which shifts the temperatures and strength of the SH-THE.

Journal article

Londo S, Biswas S, Husek J, Pinchuk IV, Newburger MJ, Boyadzhiev A, Trout AH, McComb DW, Kawakami R, Baker LRet al., 2020, Ultrafast Spin Crossover in a Room-Temperature Ferrimagnet: Element-Specific Spin Dynamics in Photoexcited Cobalt Ferrite, Journal of Physical Chemistry C, Vol: 124, Pages: 11368-11375, ISSN: 1932-7447

Transition metal complexes capable of photoinduced spin crossover have been widely investigated because of their potential to enable ultrafast optical control of information processing. However, any real application of photoswitchable molecules requires that spin crossover be paired with additional functionality such as long-range magnetic order. Important advances combining these functions are notably reported for a number of bimetallic Prussian Blue analogues; however, to date, PBA-based magnetic photoswitches can only operate below 150 K due to loss of magnetic order. In contrast, cobalt ferrite is a ferrimagnetic semiconductor with a Curie temperature of 790 K and extremely favorable magnetic properties by comparison to state-of-the-art PBAs. The mixed valence electronic structure of cobalt ferrite is reminiscent of cobalt-iron PBA, which is a well-known photoswitch. To investigate the potential for photoswitching in this material, we employ transient XUV spectroscopy to probe charge and spin dynamics with element-specific resolution on the femtosecond time scale. Results show that 400 nm light excites a metal-to-metal charge transfer transition, which drives the crossover of high-spin Co2+ to low-spin Co3+ with a time constant of 405 ± 29 fs and an internal quantum efficiency of unity. This result establishes the existence of efficient photoswitching in a new class of robust ferrimagnetic spinel ferrites.

Journal article

Lee AJ, Ahmed AS, Flores J, Guo S, Wang B, Bagués N, McComb DW, Yang Fet al., 2020, Probing the Source of the Interfacial Dzyaloshinskii-Moriya Interaction Responsible for the Topological Hall Effect in Metal/Tm_{3}Fe_{5}O_{12} Systems., Phys Rev Lett, Vol: 124

The interfacial Dzyaloshinskii-Moriya interaction (DMI) is responsible for the emergence of topological spin textures such as skyrmions in layered structures based on metallic and insulating ferromagnetic films. However, there is active debate on where the interfacial DMI resides in magnetic insulator systems. We investigate the topological Hall effect, which is an indication of spin textures, in Tm_{3}Fe_{5}O_{12} films capped with various metals. The results reveal that Pt, W, and Au induce strong interfacial DMI and topological Hall effect, while Ta and Ti cannot. This study also provides insights into the mechanism of electrical detection of spin textures in magnetic insulator heterostructures.

Journal article

Deng B, Ghatak S, Sarkar S, Singh K, Das Ghatak P, Mathew-Steiner SS, Roy S, Khanna S, Wozniak DJ, McComb DW, Sen CKet al., 2020, Novel Bacterial Diversity and Fragmented eDNA Identified in Hyperbiofilm-Forming Pseudomonas aeruginosa Rugose Small Colony Variant, iScience, Vol: 23

Microbiology; Microbiofilms

Journal article

Goodwin C, Boona S, Chen B, Hesmondhalgh O, Khan S, McComb Det al., 2020, X-ray MicroCT Imaging of Dentin Tubules in a Human Tooth, ISSN: 1431-9276

Conference paper

Hou X, Zhang X, Zhao W, Zeng C, Deng B, McComb DW, Du S, Zhang C, Li W, Dong Yet al., 2020, Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis., Nat Nanotechnol, Vol: 15, Pages: 41-46

Sepsis, a condition caused by severe infections, affects more than 30 million people worldwide every year and remains the leading cause of death in hospitals1,2. Moreover, antimicrobial resistance has become an additional challenge in the treatment of sepsis3, and thus, alternative therapeutic approaches are urgently needed2,3. Here, we show that adoptive transfer of macrophages containing antimicrobial peptides linked to cathepsin B in the lysosomes (MACs) can be applied for the treatment of multidrug-resistant bacteria-induced sepsis in mice with immunosuppression. The MACs are constructed by transfection of vitamin C lipid nanoparticles that deliver antimicrobial peptide and cathepsin B (AMP-CatB) mRNA. The vitamin C lipid nanoparticles allow the specific accumulation of AMP-CatB in macrophage lysosomes, which is the key location for bactericidal activities. Our results demonstrate that adoptive MAC transfer leads to the elimination of multidrug-resistant bacteria, including Staphylococcus aureus and Escherichia coli, leading to the complete recovery of immunocompromised septic mice. Our work provides an alternative strategy for overcoming multidrug-resistant bacteria-induced sepsis and opens up possibilities for the development of nanoparticle-enabled cell therapy for infectious diseases.

Journal article

Wang B, Esser BD, Bagués N, Williams REA, Yan J, McComb DWet al., 2019, Quantifying Jahn-Teller distortion at the nanoscale with picometer accuracy using position averaged convergent beam electron diffraction, Physical Review Research, Vol: 1, ISSN: 2643-1564

Using position averaged convergent beam electron diffraction (PACBED) the Jahn-Teller distortion in LaMnO3 is quantitatively measured using a straightforward pattern-matching approach. The fit between experimental patterns and PACBED patterns simulated using the quantum excitation of phonons model allows a three-dimensional measure of octahedral distortion and rotation information from the near transmitted disk region with picometer precision. The effects of plasmon and other inelastic components on quantification using this method are investigated and discussed. The results provide an avenue for accurate local studies of the crystal structure origins of emergent physics in parallel with high-resolution annular dark field scanning transmission electron microscopy imaging at interfaces and defects in quantum materials.

Journal article

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