Nanoscale Topography Research Articles

Single-molecule imaging of glycan-lectin interactions on cells with Glyco-PAINT.

Most lectins bind carbohydrate ligands with relatively low affinity, making the identification of optimal ligands challenging. Here we introduce a point accumulation in nanoscale topography (PAINT) super-resolution microscopy method to capture weak glycan-lectin interactions at the single-molecule level in living cells (Glyco-PAINT). Glyco-PAINT exploits weak and reversible sugar binding to directly achieve single-molecule detection and quantification in cells and is used to establish the relative kon and koff rates of a synthesized library of carbohydrate-based probes, as well as the diffusion coefficient of the receptor-sugar complex. Uptake of ligands correlates with their binding affinity and residence time to establish structure-function relations for various synthetic glycans. We reveal how sugar multivalency and presentation geometry can be optimized for binding and internalization. Overall, Glyco-PAINT represents a powerful approach to study weak glycan-lectin interactions on the surface of living cells, one that can be potentially extended to a variety of lectin-sugar interactions.

Calibration-free counting of low molecular copy numbers in single DNA-PAINT localization clusters

Single-molecule localization microscopy (SMLM) has revolutionized light microscopy by enabling optical resolution down to a few nanometer. Yet, localization precision commonly does not suffice to visually resolve single subunits in molecular assemblies or multimeric complexes. Because each targeted molecule contributes localizations during image acquisition, molecular counting approaches to reveal the target copy numbers within localization clusters have been persistently proposed since the early days of SMLM, most of which rely on preliminary knowledge of the dye photophysics or on a calibration to a reference. Previously, we developed localization-based fluorescence correlation spectroscopy (lbFCS) as an absolute ensemble counting approach for the SMLM-variant DNA-PAINT (points accumulation for imaging in nanoscale topography), for the first time, to our knowledge, circumventing the necessity for reference calibrations. Here, we present an extended concept termed lbFCS+, which allows absolute counting of copy numbers for individual localization clusters in a single DNA-PAINT image. In lbFCS+, absolute counting of fluorescent loci contained in individual nanoscopic volumes is achieved via precise measurement of the local hybridization rates of the fluorescently labeled oligonucleotides (“imagers”) employed in DNA-PAINT imaging. In proof-of-principle experiments on DNA origami nanostructures, we demonstrate the ability of lbFCS+ to truthfully determine molecular copy numbers and imager association and dissociation rates in well-separated localization clusters containing up to 10 docking strands. For N ≤ 4 target molecules, lbFCS+ is even able to resolve integers, providing the potential to study the composition of up to tetrameric molecular complexes. Furthermore, we show that lbFCS+ allows resolving heterogeneous binding dynamics, enabling the distinction of stochastically generated and a priori indistinguishable DNA assemblies. Beyond advancing quantitative DNA-PAINT imaging, we believe that lbFCS+ could find promising applications ranging from biosensing to DNA computing.

Cell spreading behaviors on hybrid nanopillar and nanohole arrays

Although nanopillars (NPs) provide a promising tool for capturing tumor cells, the effect of mixing NPs with other nanopatterns on cell behavior remains to be further studied. In this paper, a method of fabricating silicon nanoscale topographies by combining laser interference lithography with metal assisted chemical etching was introduced to investigate the behaviors and pseudopodia of A549 cells on the topologies. It was found that cells had a limited manner in spreading with small cell areas on the silicon nanopillar (SiNP) arrays, but a good manner in spreading with large cell areas on the silicon nanohole (SiNH) arrays. When on the hybrid SiNP/SiNH arrays, cells had medium cell areas and they arranged orderly along the boundaries of SiNPs and SiNHs, as well as 80% of cells displayed a preference for SiNPs over SiNHs. Furthermore, the lamellipodia and filopodia are dominant in the hybrid SiNP/SiNH and SiNP arrays, respectively, both of them are dominant in the SiNH arrays. In addition, the atomic force acoustic microscopy was also employed to detect the subsurface features of samples. The results suggest that the hybrid SiNP/SiNH arrays have a targeted trap and elongation effect on cells. The findings provide a promising method in designing hybrid nanostructures for efficient tumor cell traps, as well as regulating the cell behaviors and pseudopodia.

Nanoscale hybrid implant surfaces and Osterix-mediated osseointegration.

Endosseous implant surface topography directly affects adherent cell responses following implantation. The aim of this study was to examine the impact of nanoscale topographic modification of titanium implants on Osterix gene expression since this gene has been reported as key factor for bone formation. Titanium implants with smooth and nanoscale topographies were implanted in the femurs of Osterix-Cherry mice for 1-21 days. Implant integration was evaluated using scanning electron microscopy (SEM) to evaluate cell adhesion on implant surfaces, histology, and nanotomography (NanoCT) to observe and quantify the formed bone-to-implant interface, flow cytometry to quantify of Osterix expressing cells in adjacent tissues, and real-time PCR (qPCR) to quantify the osteoinductive and osteogenic gene expression of the implant-adherent cells. SEM revealed topography-dependent adhesion of cells at early timepoints. NanoCT demonstrated greater bone formation at nanoscale implants and interfacial osteogenesis was confirmed histologically at 7 and 14 days for both smooth and nanosurface implants. Flow cytometry revealed greater numbers of Osterix positive cells in femurs implanted with nanoscale versus smooth implants. Compared to smooth surface implants, nanoscale surface adherent cells expressed higher levels of Osterix (Osx), Alkaline phosphatase (Alp), Paired related homeobox (Prx1), Dentin matrix protein 1 (Dmp1), Bone sialoprotein (Bsp), and Osteocalcin (Ocn). In conclusion, nanoscale surface implants demonstrated greater bone formation associated with higher levels of Osterix expression over the 21-day healing period with direct evidence of surface-associated gene regulation involving a nanoscale-mediated osteoinductive pathway that utilizes Osterix to direct adherent cell osteoinduction.

The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration

The initial cellular and molecular activities at the bone interface of implants with controlled nanoscale topography and microscale roughness have previously been reported. However, the effects of such surface modifications on the development of osseointegration have not yet been determined. This study investigated the molecular events and the histological and biomechanical development of the bone interface in implants with nanoscale topography, microscale roughness or a combination of both. Polished and machined titanium implants with and without controlled nanopatterning (75 nm protrusions) were produced using colloidal lithography and coated with a thin titanium layer to unify the chemistry. The implants were inserted in rat tibiae and subjected to removal torque (RTQ) measurements, molecular analyses and histological analyses after 6, 21 and 28 days. The results showed that nanotopography superimposed on microrough, machined, surfaces promoted an early increase in RTQ and hence produced greater implant stability at 6 and 21 days. Two-way MANOVA revealed that the increased RTQ was influenced by microscale roughness and the combination of nanoscale and microscale topographies. Furthermore, increased bone-implant contact (BIC) was observed with the combined nanopatterned machined surface, although MANOVA results implied that the increased BIC was mainly dependent on microscale roughness. At the molecular level, the nanotopography, per se, and in synergy with microscale roughness, downregulated the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In conclusion, controlled nanotopography superimposed on microrough machined implants promoted implant stability during osseointegration. Nanoscale-driven mechanisms may involve attenuation of the inflammatory response at the titanium implant site. Statement of SignificanceThe role of combined implant microscale and nanotopography features for osseointegration is incompletely understood. Using colloidal lithography technique, we created an ordered nanotopography pattern superimposed on screwshaped implants with microscale topography. The midterm and late molecular, bone-implant contact and removal torque responses were analysed in vivo. Nanotopography superimposed on microrough, machined, surfaces promoted the implant stability, influenced by microscale topography and the combination of nanoscale and microscale topographies. Increased bone-implant contact was mainly dependent on microscale roughness whereas the nanotopography, per se, and in synergy with microscale roughness, attenuated the proinflammatory tumor necrosis factor alpha (TNF-α) expression. It is concluded that microscale and nanopatterns provide individual as well as synergistic effects on molecular, morphological and biomechanical implant-tissue processes in vivo.

Telomerase detection using a DNA-PAINT strategy

Telomerase plays an important role in maintaining the length of telomere during cell division and is recognized as a new kind of biomarkers for cancer diagnosis. In this work, we present a brand new telomerase detection strategy based on a DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) like strategy. With an extraordinary spatial resolution (∼10 nm), the DNA-PAINT based strategy offers several advantages. First, it avoids complicated polymerase chain reaction and electrophoresis procedures. Second, it enables super resolution imaging of the reaction products with a high signal-to-noise ratio and facilitates the location of telomeric elongation sites on the single particle level, which results in a high sensitivity. Third, the detection scheme of the DNA-PAINT strategy allows direct in situ visualization of the telomeric elongation process, which has never been achieved before. All these advantages make the DNA-PAINT telomerase detection strategy significant for dynamic investigation of telomerase related physiological processes as well as cancer diagnosis.

Anodic TiO2 Nanotubes: Tailoring Osteoinduction via Drug Delivery.

TiO2 nanostructures and more specifically nanotubes have gained significant attention in biomedical applications, due to their controlled nanoscale topography in the sub-100 nm range, high surface area, chemical resistance, and biocompatibility. Here we review the crucial aspects related to morphology and properties of TiO2 nanotubes obtained by electrochemical anodization of titanium for the biomedical field. Following the discussion of TiO2 nanotopographical characterization, the advantages of anodic TiO2 nanotubes will be introduced, such as their high surface area controlled by the morphological parameters (diameter and length), which provides better adsorption/linkage of bioactive molecules. We further discuss the key interactions with bone-related cells including osteoblast and stem cells in in vitro cell culture conditions, thus evaluating the cell response on various nanotubular structures. In addition, the synergistic effects of electrical stimulation on cells for enhancing bone formation combining with the nanoscale environmental cues from nanotopography will be further discussed. The present review also overviews the current state of drug delivery applications using TiO2 nanotubes for increased osseointegration and discusses the advantages, drawbacks, and prospects of drug delivery applications via these anodic TiO2 nanotubes.

Mechanistic Insight in Surface Nanotopography Driven Cellular Migration.

Cellular migration plays a vital role in many physiological processes. To elucidate the role of surface nanotopography on the downstream signaling pathways underlying cell migration, model surfaces having well-defined hill-like surface nanotopography and uniform surface chemistry were designed and implemented using plasma polymerization and covalent attachment of nanoparticles of predetermined size. A scratch wound assay, immunostaining, and gene expression of focal adhesion (FA) proteins were performed to determine the influence of surface nanotopography on cell migration. The results of this study demonstrate that the gap closure between cell monolayers is faster on surfaces having greater nanoscale topography. The phenomenon is predominantly driven by cell migration and was independent from cell proliferation. Qualitative and quantitative assessment of proteins involved in the signaling pathways underlying cell migration showed significant modulation by surface nanotopography. Specifically, focal adhesion sites decreased with the increase in surface nanotopography scale while the expression of FA proteins increased. This implies that nanotopography mediated modulation of cell migration is directly governed by the recruitment of receptor and adapter proteins responsible for cell-surface interaction. The results of this study indicate that biomaterial devices and constructs having rationally designed surface nanotopography and chemistry could be utilized to regulate wound healing and tissue regeneration.

Machine learning model for understanding laser superhydrophobic surface functionalization

A general machine learning (ML) framework of surface wetting is proposed by considering a broad range of factors, including solid surface topography, solid surface chemistry, liquid properties, and environmental conditions. In particular, an XGBoost-based ML model is demonstrated for learning the surface wetting behaviors processed by a laser-based surface functionalization process, namely nanosecond laser-based high-throughput surface nanostructuring (nHSN). This is the first known attempt to apply machine learning to surface wetting by considering both surface topography and surface chemistry properties. Novel microscale and nanoscale topography parameters viz., roughness, fractal, entropy, feature periodicity are defined with suitable computer algorithms to comprehensively describe the surface topography. A novel set of surface chemistry parameters such as polarity, volume, and amount of functional groups are also used as the machine learning model input. Upon analyzing the importance of each parameter for the nHSN process, surface chemistry shows the greatest importance in determination of surface wettability, while surface morphology also plays a part in influencing the wettability. • A machine learning model is firstly proposed for surface wettability considering both topography and chemistry. • Fractal dimension, 2D-entropy, and periodicity are used to describe surface morphology. • Polarity and functional groups are used to describe surface chemistry. • The results showed that the surface chemistry is the dominant feature while surface topography plays a supportive role.

Advanced spatial investigation of 3D nanoscale topography of DyMnO3 thin films

We have synthesized DyMnO3 thin films using a sol gel method. Our goal was to evaluate the spatial patterns of the films as a function of the annealing temperature. The results reveal that from 800 °C, the films present pure orthorhombic structure with decreasing of nanocrystal size. The topography shows that films sintered at higher temperatures have greater surface roughness, negative asymmetries, high kurtosis, high peak densities and pointed peak shapes. These films also have anisotropic surfaces and are dominated by low spatial frequencies than films sintered at lower temperatures. However, fractal parameters show the sample sintered at 800 °C has greater spatial complexity, less heterogeneous nanotexture, ideal surface porosity, and greater topographic uniformity. These results suggest the film sintered at 800 °C has spatial configuration with the best topographic features which can be of great interest for technological application, regarding the processing control of perovskite rare-earth oxides-based semiconductor films.

Carbon nanotube-mediated three-dimensional vanadium oxide nanoarchitectures with tunable morphology and translatable functionality

A carbon nanotube (CNT)-mediated three-dimensional (3D) vanadium pentoxide (V2O5) nanoarchitecture with tunable morphology and translatable electrical and electrochemical functionality is developed via the step-wise chemical vapor deposition. Controlling the pressure, gas flow, and growth time, based on the collective understanding of the vapor-solid growth mechanism, enables the tailoring of V2O5 nanostructures into diverse functional structures including nanowires, nanoribbons, and nanoplatelets, where the nanoscale topography of an underlying CNT surface facilitates the conformal 3D morphing with extended scale, density, and surface area. An in-depth analysis of the V2O5-CNT interface confirms that the highly crystalline V2O5 nanocrystals are firmly connected to the CNTs with their structural and functional characteristics maintained. Here we demonstrate that the growth process and consequently emerging functionality of the 3D V2O5/CNT hybrid architecture can be translated to various practical frameworks such as porous metallic micromesh with further enhanced surface area and electrochemical conversion. The 3D V2O5/CNT hybrid architecture with application-specific structural tunability may thus be applicable to broader materials and device systems for energy conversion, sensing, photonics, and many others.

Materials with Hierarchical Porosity Enhance the Stability of Infused Ionic Liquid Films.

Defined surface functionalities can control the properties of a material. The layer-by-layer method is an experimentally simple yet very versatile method to coat a surface with nanoscale precision. The method is widely used to either control the chemical properties of the surface via the introduction of functional moieties bound to the polymer or create nanoscale surface topographies if one polymeric species is replaced by a colloidal dispersion. Such roughness can enhance the stability of a liquid film on top of the surface by capillary adhesion. Here, we investigate whether a similar effect allows an increased retention of liquid films within a porous surface and thus potentially increases the stability of ionic liquid films infused within a porous matrix in the supported ionic liquid-phase catalysis. The complex geometry of the porous material, long diffusion pathways, and small sizes of necks connecting individual pores all contribute to difficulties to reliably coat the required porous materials. We optimize the coating process to ensure uniform surface functionalization via two steps. Diffusion limitations are overcome by force-wetting the pores, which transports the functional species convectively into the materials. Electrostatic repulsion, which can limit pore accessibility, is mitigated by the addition of electrolytes to screen charges. We introduce nanoscale topography in microscale porous SiC monoliths to enhance the retention of an ionic liquid film. We use γ-Al2O3 to coat monoliths and test the retention of 1-butyl-2,3-dimethylimidazolium chloride under exposure to a continuous gas stream, a setup commonly used in the water-gas shift reaction. Our study showcases that a hierarchical topography can improve the stability of impregnated ionic liquid films, with a potential advantage of improved supported ionic liquid-phase catalysis.

Peptide-PAINT Enables Investigation of Endogenous Talin with Molecular Scale Resolution in Cells and Tissues.

Talin is a cell adhesion molecule that is indispensable for the development and function of multicellular organisms. Despite its central role for many cell biological processes, suitable methods to investigate the nanoscale organization of talin in its native environment are missing. Here, we overcome this limitation by combining single‐molecule resolved PAINT (points accumulation in nanoscale topography) imaging with the IRIS (image reconstruction by integrating exchangeable single‐molecule localization) approach, enabling the quantitative analysis of genetically unmodified talin molecules in cells. We demonstrate that a previously reported peptide can be utilized to specifically label the two major talin isoforms expressed in mammalian tissues with a localization precision of <10 nm. Our experiments show that the methodology performs equally well as state‐of‐the‐art single‐molecule localization techniques, and the first applications reveal a thus far undescribed cell adhesion structure in differentiating stem cells. Furthermore, we demonstrate the applicability of this peptide‐PAINT technique to mouse tissues paving the way to single‐protein imaging of endogenous talin proteins under physiologically relevant conditions.

Site-Specifically-Labeled Antibodies for Super-Resolution Microscopy Reveal In Situ Linkage Errors.

The precise spatial localization of proteins in situ by super-resolution microscopy (SRM) demands their targeted labeling. Positioning reporter molecules as close as possible to the target remains a challenge in primary cells or tissues from patients that cannot be easily genetically modified. Indirect immunolabeling introduces relatively large linkage errors, whereas site-specific and stoichiometric labeling of primary antibodies relies on elaborate chemistries. In this study, we developed a simple two-step protocol to site-specifically attach reporters such as fluorophores or DNA handles to several immunoglobulin G (IgG) antibodies from different animal species and benchmarked the performance of these conjugates for 3D STORM (stochastic optical reconstruction microscopy) and DNA-PAINT (point accumulation in nanoscale topography). Glutamine labeling was restricted to two sites per IgG and saturable by exploiting microbial transglutaminase after removal of N-linked glycans. Precision measurements of 3D microtubule labeling shell dimensions in cell lines and human platelets showed that linkage errors from primary and secondary antibodies did not add up. Monte Carlo simulations of a geometric microtubule-IgG model were in quantitative agreement with STORM results. The simulations revealed that the flexible hinge between Fab and Fc segments effectively randomized the direction of the secondary antibody, while the restricted binding orientation of the primary antibody’s Fab fragment accounted for most of the systematic offset between the reporter and α-tubulin. DNA-PAINT surprisingly yielded larger linkage errors than STORM, indicating unphysiological conformations of DNA-labeled IgGs. In summary, our cost-effective protocol for generating well-characterized primary IgG conjugates offers an easy route to precise SRM measurements in arbitrary fixed samples.

Correlative Super-Resolution and Atomic Force Microscopy of DNA Nanostructures and Characterization of Addressable Site Defects.

To bring real-world applications of DNA nanostructures to fruition, advanced microscopy techniques are needed to shed light on factors limiting the availability of addressable sites. Correlative microscopy, where two or more microscopies are combined to characterize the same sample, is an approach to overcome the limitations of individual techniques, yet it has seen limited use for DNA nanotechnology. We have developed an accessible strategy for high resolution, correlative DNA-based points accumulation for imaging in nanoscale topography (DNA-PAINT) super-resolution and atomic force microscopy (AFM) of DNA nanostructures, enabled by a simple and robust method to selectively bind DNA origami to cover glass. Using this technique, we examined addressable "docking" sites on DNA origami to distinguish between two defect scenarios-structurally incorporated but inactive docking sites, and unincorporated docking sites. We found that over 75% of defective docking sites were incorporated but inactive, suggesting unincorporated strands played a minor role in limiting the availability of addressable sites. We further explored the effects of strand purification, UV irradiation, and photooxidation on availability, providing insight on potential sources of defects and pathways toward improving the fidelity of DNA nanostructures.

Facile fabrication of ordered discontinuous nanotopography on photosensitive substrates for enhanced neuronal differentiation

Controlling the development and morphology of neurons is important for basic neuroscience research as well as for applications in nerve regeneration and neural interfaces. Various studies have shown that nanoscale topographies can promote the development of neuronal cells and the differentiation of neural stem cells; however, the fabrication of these nanotopographical features often involves expensive and sophisticated techniques. Here, we employ nanosphere lens lithography combined with UV-LED technology to create nanopatterns on an SU-8 photoresist. We develop a facile method to create a reusable polystyrene nanosphere (PS-NS) lens array by the spontaneous formation of a hexagonal close-packed array of PS-NSs at a water–air interface and its subsequent transfer to a polydimethylsiloxane carrier film without using any special equipment. We show that this simple technique can create ordered arrays of nanodots on an SU-8 film, the dimensions of which can be controlled by the size of the PS-NSs. When used as a substrate for the neuronal differentiation of pheochromocytoma (PC12) cells, the nanopatterned SU-8 films exhibit enhanced differentiation parameters with respect to conventional tissue culture plastic as compared with their flat counterparts. The method proposed here can greatly facilitate the nanopatterning of various photosensitive substrates for the development of implants for nerve regeneration and neural interfacing.

Simultaneous Intelligent Imaging of Nanoscale Reactivity and Topography by Scanning Electrochemical Microscopy.

Scanning electrochemical microscopy (SECM) enables reactivity and topography imaging of single nanostructures in the electrolyte solution. The in situ reactivity and topography, however, are convoluted in the real-time image, thus requiring another imaging method for subsequent deconvolution. Herein, we develop an intelligent mode of nanoscale SECM to simultaneously obtain separate reactivity and topography images of non-flat substrates with reactive and inert regions. Specifically, an ∼0.5 μm-diameter Pt tip approaches a substrate with an ∼0.15 μm-height active Au band adjacent to an ∼0.4 μm-wide slope of the inactive glass surface followed by a flat inactive glass region. The amperometric tip current versus tip-substrate distance is measured to observe feedback effects including redox-mediated electron tunneling from the substrate. The intelligent SECM software automatically terminates the tip approach depending on the local reactivity and topography of the substrate under the tip. The resultant short tip-substrate distances allow for non-contact and high-resolution imaging in contrast to other imaging modes based on approach curves. The numerical post-analysis of each approach curve locates the substrate under the tip for quantitative topography imaging and determines the tip current at a constant distance for topography-independent reactivity imaging. The nanoscale grooves are revealed by intelligent topography SECM imaging as compared to scanning electron microscopy and atomic force microscopy without reactivity information and as unnoticed by constant-height SECM imaging owing to the convolution of topography with reactivity. Additionally, intelligent reactivity imaging traces abrupt changes in the constant-distance tip current across the Au/glass boundary, which prevents constant-current SECM imaging.

(Invited) Controlling Nano-Scale Chemically Modified Thin Films for Chemical Mechanical Planarization

This is a review paper on the effect of chemicals modified thin films on CMP process development. As the microelectronics manufacturing faces the challenges related to the Beyond Moore’s Scale adaptation, Chemical Mechanical Planarization (CMP) process control becomes much more critical yet difficult simultaneously. The need for planarizing larger scale wafers at an atomic scale precision with superior removal rate selectivity and zero defect focus demands a nano-scale control on the process performance. This study reviews the atomic scale chemical and mechanical interactions on CMP as it applies to traditional as well as the next generation materials in microelectronics manufacturing. Once the behavior of the wafer surface is understood at an atomic level, the process control metrics can be tuned accordingly.In an attempt to come up with the design criteria for the slurry chemistry, chemically modified layer formation is evaluated on conducting, semiconducting and insulating materials as a function of evaluating the nano-scale surface topography and change in surface energy. Metallic films are studied in terms of their corrosion and passivation behavior through macro-scale electrochemical evaluations as well as the surface sensitive characterization techniques such as XRR, XRD and FTIR [1, 2]. In addition, a modeling approach is introduced through Cahn Hilliard Equation (CHE) approximation to the surface energy minimization on the metal-oxide formation by nucleation [3]. Furthermore, removal rate selectivity properties of the semiconductor materials are discussed on conventional and III-V semiconductors and insulators as a function of chemically modified film alteration [4-5]. Some high-end applications such as (i) tungsten T-gate transistors, (ii) new liner/barrier materials [6], (iii) germanium based high-speed, shallow trench isolation transistors and (iv) high-power transistors and LED applications where III/V semiconductors are deliberated. As a new challenge, 3-D implementations of the CMP process, where the chemically modified nano-films impact the materials performance are also introduced. Ozdemir, Basim, G.B. "Effect of Chemical Mechanical Polishing on Surface Nature of Titanium Implants FT-IR and Wettability Data of Titanium Implants Surface After Chemical Mechanical Polishing Implementation," Data, in Brief, 10, P 20-25, 2017. Karagoz, A., and Basim, G.B. “Controlling Germanium CMP Selectivity through Slurry Mediation by Surface Active Agents," ECS Journal of Solid State Science and Technology, CMP Special Issue, 4 (11) P5097-P5104, 2015. Karagoz, A., Sengul, , Basim, G.B., “A Cahn Hilliard Modeling of Metal Oxide Thin Films for Advanced CMP Applications," 225th ECS Meeting – Orlando, Florida, USA, May 11-15, 2014, ECS Transactions, 61 (17) 15-20 (2014). Karagoz, A., Craciun, V., Basim, G.B., “Characterization of Nano-Scale Protective Oxide Films_ Application on Metal Chemical Mechanical Planarization”. ECS Journal of Solid State Science and Technology, 4 (2) P1-P8, 2015. Ozbek, S., Akbar, W., Basim, G.B. “ Optimized Process Design for GaN Chemical Mechanical Planarization” ECS Journal of Solid State Science and Technology, Special Issue on GaN-Based Electronics for Power, RF, and Rad-Hard Applications , 6-11, P S3084-S3092, 2017. Yagan, R., Basim, G.B., “A Fundamental Approach to Electrochemical Analyses on Chemically Modified Thin Films for Barrier CMP Optimization," ECS J. Solid State Sci. Technol. 8-5, P3118-P3127, 2019.

Direct measurement of fungal contribution to silicate weathering rates in soil

AbstractChemical weathering produces solutes that control groundwater chemistry and supply ecosystems with essential nutrients. Although microbial activity influences silicate weathering rates and associated nutrient fluxes, its relative contribution to silicate weathering in natural settings remains largely unknown. We provide the first quantitative estimates of in situ silicate weathering rates that account for microbially induced dissolution and identify microbial actors associated with weathering. Nanoscale topography measurements showed that fungi colonizing olivine [(Mg,Fe)2SiO4] samples in a Mg-deficient forest soil accounted for up to 16% of the weathering flux after 9 mo of incubation. A local increase in olivine weathering rate was measured and attributed to fungal hyphae of Verticillium sp. Altogether, this approach provides quantitative parameters of bioweathering (i.e., rates and actors) and opens new avenues to improve elemental budgets in natural settings.

Nanowire Based Mechanostimulating Platform for Tunable Activation of Natural Killer Cells

AbstractThe understanding of the activation mechanism of natural killer (NK) cells has been traditionally based on the biochemical interaction of NK cell receptors with the ligands presenting on target cells. Yet, how physical features of the NK cell environment, such as stiffness and nanoscale topography, regulate the activity of NK cells, is unknown. An artificial microenvironment is developed for NK cell stimulation based on variably elongated nanowires functionalized with activating antigens and used it as a tunable model system to study the separate and cumulative effects of elasticity and nanotopography on NK cell activation. It is found that late signaling, degranulation, and cytokine production in NK cells consistently vary with nanowire length, and it is maximized for the longest nanowires, measuring ≈20 µm in length. Intriguingly, a similar trend is observed for nanowires lacking antigens, albeit with a lower activation magnitude overall, indicating that chemical and mechanical stimuli independently determine the activation of NK cells. The demonstrated tuning of the activation of NK cells by nanoscale physical features of their environment not only provides an important insight into the regulation mechanism of these lymphocytes, but also paves the way to rationally designed nanomaterials for controlled ex vivo activation of NK cells in immunotherapy.