Nanoscale Topographic Features Research Articles

New metrics for describing atomic force microscopy data of nanostructured surfaces through topological data analysis

The nanoscale topographic features of surfaces, such as vertical, lateral, and multiscale structures, are essential for understanding and identifying correlations with properties in various applications. These features are critical in applications ranging from biomedical devices to electronic components, as they play a significant role in determining the functionality of these systems. Despite the capabilities of traditional surface analysis methods, which rely on standard vertical profile and area measurements, these techniques often fail to capture the subtle and specific features that differentiate between surfaces with different morphologies. To address this challenge, this paper proposes applying of a topological data analysis of atomic force microscopy data to create a unique topological signature for each surface. This approach can help us better understand complex relationships between topography and functional characteristics in various applications and enable further advanced surface comparison.

Single-cell fluid-based force spectroscopy reveals near lipid size nano-topography effects on neural cell adhesion.

Nano-roughness has shown great potential in enhancing high-fidelity electrogenic cell interfaces, owing to its characteristic topography comparable to proteins and lipids, which influences a wide range of cellular mechanical responses. Gaining a comprehensive understanding of how cells respond to nano-roughness at the single-cell level is not only imperative for implanted devices but also essential for tissue regeneration and interaction with complex biomaterial surfaces. In this study, we quantify cell adhesion and biomechanics of single cells to nano-roughened surfaces by measuring neural cell adhesion and biomechanics via fluidic-based single-cell force spectroscopy (SCFS). For this, we introduce nanoscale topographical features on polyimide (PI) surfaces achieving roughness up to 25 nm without chemical modifications. Initial adhesion experiments show cell-specific response to nano-roughness for neuroblastoma cells (SH-SY5Y) compared to human astrocytes (NHA) around 15 and 20 nm surface roughness. In addition, our SCFS measurements revealed a remarkable 2.5-fold increase in adhesion forces (150-164 nN) for SH-SY5Y cells cultured on roughened PI (rPI) surfaces compared to smooth surfaces (60-107 nN). Our data also shows that cells can distinguish changes in nano-roughness as small 2 nm (close to the diameter of a single lipid) and show roughness dependence adhesion while favoring 15 nm. Notably, this enhanced adhesion is accompanied by increased cell elongation upon cell detachment without any significant differences in cell area spreading. The study provides valuable insights into the interplay between nano-topography and cellular responses and offers practical implications for designing biomaterial surfaces with enhanced cellular interactions.

Mapping nanoscale topographic features in thick tissues with speckle diffraction tomography

Resolving three-dimensional morphological features in thick specimens remains a significant challenge for label-free imaging. We report a new speckle diffraction tomography (SDT) approach that can image thick biological specimens with ~500 nm lateral resolution and ~1 μm axial resolution in a reflection geometry. In SDT, multiple-scattering background is rejected through spatiotemporal gating provided by dynamic speckle-field interferometry, while depth-resolved refractive index maps are reconstructed by developing a comprehensive inverse-scattering model that also considers specimen-induced aberrations. Benefiting from the high-resolution and full-field quantitative imaging capabilities of SDT, we successfully imaged red blood cells and quantified their membrane fluctuations behind a turbid medium with a thickness of 2.8 scattering mean-free paths. Most importantly, we performed volumetric imaging of cornea inside an ex vivo rat eye and quantified its optical properties, including the mapping of nanoscale topographic features of Dua’s and Descemet’s membranes that had not been previously visualized.

Probing interaction forces associated with calcite scaling in aqueous solutions by atomic force microscopy

The prevention of calcite aggregation and scaling remains a challenging problem in aqueous based systems and environmental science. Decades of research studies have proposed microscopic mechanisms of aggregation control, but experiments at the nanoscale and molecular level are rarely conducted. Here we show that the nanoscale topographic features of calcite during its aggregation depend significantly on the intermolecular and surface forces involved in this process. By measuring the forces between a calcite or silica particle and a calcite surface in aqueous solutions using atomic force microscopy, we found that higher solution pH and inhibitor concentration and lower salinity resulted in a system of stronger repulsion and weaker adhesion, which is favorable for reducing the possibility of calcite aggregation and surface deposition. Conflicting roles of Mg2+ in calcite aggregation prevention, being positive in acidic pH and negative in alkaline pH, were also observed. The nanoscale structural changes of calcite, visualized by atomic force microscopy or scanning electron microscopy, indicated a size dependence of aggregated and deposited calcite crystals on the calcite-calcite and calcite-silica interactions, respectively. The generalized framework of the calcite aggregation mechanism achieved in this work can be extended to other types of systems and provides a basis for investigating the anti-aggregation strategy of calcite from industrial and environmental perspectives.

Surface topography and free energy regulate osteogenesis of stem cells: effects of shape-controlled gold nanoparticles.

ABSTRACTThe surface free energy of a biomaterial plays an important role in the early stages of cell–biomaterial interactions, profoundly influencing protein adsorption, interfacial water accessibility, and cell attachment on the biomaterial surface. Although multiple approaches have been developed to engineer the surface free energy of biomaterials, systematically tuning their surface free energy without altering other physicochemical properties remains challenging. In this study, we constructed an array of chemically-equivalent surfaces with comparable apparent roughness through assembly of gold nanoparticles adopting various geometrically-distinct shapes but all capped with the same surface ligand, (1-hexadecyl)trimethylammonium chloride, on cell culture substrates. We found that bone marrow stem cells exhibited distinct osteogenic differentiation behaviours when interacting with different types of substrates comprising shape-controlled gold nanoparticles. Our results reveal that bone marrow stem cells are capable of sensing differences in the nanoscale topographical features, which underscores the role of the surface free energy of nanostructured biomaterials in regulating cell responses. The study was approved by Institutional Animal Care and Use Committee, School of Medicine, University of South Carolina.

Spectroscopy-Assisted Label-free Molecular Analysis of Live Cell Surface with Vertically Aligned Plasmonic Nanopillars.

A generalized label-free platform for surface-selective molecular sensing in living cells can transform the ability to examine complex events in the cell membrane. While vertically aligned semiconductor and metal-semiconductor hybrid nanopillars have rapidly surfaced for stimulating and probing the intracellular environment, the potential of such constructs for selectively interrogating the cell membrane is surprisingly underappreciated. In this work, a new platform, entitled nano-PROD (nano-pillar based Raman optical detection), enables molecular recording by probing fundamental vibrational modes of membrane constituents of cells adherent on a large-area silver-coated silicon nanopillar substrate fabricated using a precursor solution-based nanomanufacturing process. It is shown that the nano-PROD platform sustains live cells in near-physiological conditions, which can be directly profiled using surface-enhanced Raman spectroscopy due to the confined electromagnetic field enhancement. The experimental results highlight the utility of the platform in probing specific cell surface markers for accurately recognizing the phenotypically identical prostate cancer cells, differing only in prostate-specific membrane antigen expression. Due to its tunability, nano-PROD has the promise to be readily extendable to other applications that can leverage its unique combination of nanoscale topographic features and molecular sensing capabilities, from stain-free cytopathology inspection to understanding spatio-mechanical regulation in membrane receptor function.

Directional Osteo-Differentiation Effect of hADSCs on Nanotopographical Self-Assembled Polystyrene Nanopit Surfaces.

IntroductionCells exhibit high sensitivity and a diverse response to the nanotopography of the extracellular matrix, thereby endowing materials with instructive performances formerly reserved for growth factors. This finding leads to opportunities for improvement. However, the interplay between the topographical surface and cell behaviors remains incompletely understood.MethodsIn the present study, we showed nanosurfaces with various dimensions of nanopits (200–750 nm) fabricated by self-assembling polystyrene (PS) nanospheres. Human adipose-derived stem cell behaviors, such as cell morphology, adhesion, cytoskeleton contractility, proliferation, and differentiation, were investigated on the prepared PS nanopit surface.ResultsThe osteogenic differentiation can be enhanced by nanopits with a diameter of 300–400 nm.DiscussionThe present study provided exciting new avenues to investigate cellular responses to well-defined nanoscale topographic features, which could further guide bone tissue engineering and stem cell clinical research. The capability to control developing biomaterials mimicking nanotopographic surfaces promoted functional tissue engineering, such as artificial joint replacement, bone repair, and dental applications.

CO2 wetting on pillar-nanostructured substrates

CO2 capture by dropwise CO2 condensation on cold solid surfaces is a promising technology. Understanding the role of the nanoscale surface and topographical features of CO2 droplet wetting characteristics is of importance for CO2 capture by this technology, but this remains unexplored as of yet. Here, using large-scale molecular dynamics (MD) simulations, the contact angle and wetting behaviors of CO2 droplets on pillar-structured Cu-like surfaces are investigated for the first time. Dynamic wetting simulations show that, by changing the strength of the solid–liquid attraction a smooth Cu-like surface offers a transition from CO2-philic to CO2-phobic. By periodically pillared roughening of the Cu-like surfaces, however, a higher contact angle and a smaller spreading exponent of a liquid CO2 droplet are realized. Particularly, a critical crossover of CO2-philic to CO2-phobic can appear. The wetting of the pillared surfaces by a liquid CO2 droplet proceeds non-uniformly. A liquid CO2 droplet is capable of exhibiting a transition from the Cassie state to the Wenzel state with increasing increasing inter-pillar distance, and increasing pillar width. The wetting morphologies of the metastable Wenzel state of a CO2 droplet are very different from each other. The findings will inform the ongoing design of CO2-phobic solid surfaces for practical dropwise condensation-based CO2 capture applications.

Microscopic and Spectroscopic Characterization of Nanostructured Topographical Surface of Rattlesnake Rattle.

Rattlesnakes are easily recognized by a rattle on the tail. Despite the advances in molecular, morphological, and evolutionary studies about several aspects of rattles, there are no studies elucidating these nanoscale topographical features using high-resolution techniques. Here we propose a set of approaches to show these micro/nano surface features searching for patterns or hidden signatures. The results showed that the older rattle ring (segment 8) presented higher roughness values when compared to other segments. Cluster analysis allowed the observation of similarities/differences among some groups, which reinforced the strong discrepancy of the segment 8 when compared to the others and enable possible topographical transitions among each segment features, considering their linkages and Euclidean distances. Attractive forces and surface hardness were also significant increased on segment 8, while adhesion was significantly decreased on the segments 5, 6, and 7 compared to segment 1 (P < 0.05). Fourier transform infrared spectroscopy showed typical profiles of keratin spectra considering the amino acids present in this protein structure. Energy dispersive spectroscopy results indicated possible different molecular composition on each segment. These set of approaches applied on the present study represents an array of new possibilities towards the qualitative and quantitative analyses of this type of biomaterials enabling to address several structural, chemical and mechanical questions ongoing on scientific world.

Tip-Enhanced Raman Nanographs of Plasmonic Silver Nanoparticles

Tip-enhanced Raman scattering (TERS) from plasmonic silver nanoparticles traces spatial variations in optical fields defined by the interaction of the plasmonic probe with nanoscale topographic features that are characteristic of crystalline particles. This is demonstrated through correlated atomic force microscopy (AFM)–TERS imaging of ∼100 nm silver nanoparticles coated with 4-mercaptobenzonitrile (MBN) molecules. In effect, the recorded spectral images are sensitive to the 3D topographic makeup of the particle and broadcast local optical fields that vary over a few nanometers of length scale.

The effects of collector geometry on the internal structure of the 3D nanofiber scaffold fabricated by divergent electrospinning

Latest bioinspired approaches in tissue engineering focus on the creation of biomaterials with micro- and nanoscale topographical features. Various additive manufacturing techniques have been applied for scaffold fabrication; however, creating three dimensional (3D) nanofiber structure within a scaffold remains to be challenging. This paper presented an innovative divergence electrospinning strategy to fabricate 3D polycaprolactone (PCL) scaffolds comprised of uniaxially aligned nanofibers. The effects of collector geometry on the nanofiber structure were characterized by polynomial regression analysis. The length-to-width ratio and inclination angle of the collector were found to be critical to nanofiber distribution within the 3D scaffold. The nanofiber orientation was consistent with the direction of electric field vectors between the two bevels of the collector. After a continuous culturing for 7 days, fibroblast cells were uniaxially organized within the 3D scaffolds, closely resembling the fibrous structure in musculoskeletal tissues. This study provided a novel approach to biomimetic native tissue microstructures and showed a great potential as a future fabrication additive manufacturing platform for tissue engineering.

Tunable 3D Nanofiber Architecture of Polycaprolactone by Divergence Electrospinning for Potential Tissue Engineering Applications

The creation of biomimetic cell environments with micro and nanoscale topographical features resembling native tissues is critical for tissue engineering. To address this challenge, this study focuses on an innovative electrospinning strategy that adopts a symmetrically divergent electric field to induce rapid self-assembly of aligned polycaprolactone (PCL) nanofibers into a centimeter-scale architecture between separately grounded bevels. The 3D microstructures of the nanofiber scaffolds were characterized through a series of sectioning in both vertical and horizontal directions. PCL/collagen (type I) nanofiber scaffolds with different density gradients were incorporated in sodium alginate hydrogels and subjected to elemental analysis. Human fibroblasts were seeded onto the scaffolds and cultured for 7 days. Our studies showed that the inclination angle of the collector had significant effects on nanofiber attributes, including the mean diameter, density gradient, and alignment gradient. The fiber density and alignment at the peripheral area of the 45°-collector decreased by 21% and 55%, respectively, along the z-axis, while those of the 60°-collector decreased by 71% and 60%, respectively. By altering the geometry of the conductive areas on the collecting bevels, polyhedral and cylindrical scaffolds composed of aligned fibers were directly fabricated. By using a four-bevel collector, the nanofibers formed a matrix of microgrids with a density of 11%. The gradient of nitrogen-to-carbon ratio in the scaffold-incorporated hydrogel was consistent with the nanofiber density gradient. The scaffolds provided biophysical stimuli to facilitate cell adhesion, proliferation, and morphogenesis in 3D.

Physical ageing of spreading droplets in a viscous ambient phase

In this work, we study the spontaneous spreading of water droplets immersed in oil and report an unexpectedly slow kinetic regime not described by previous spreading models. We can quantitatively describe the observed regime crossover and spreading rate in the late kinetic regime with an analytical model considering the presence of periodic metastable states induced by nanoscale topographic features (characteristic area ~4 nm2, height ~1 nm) observed via atomic force microscopy. The analytical model proposed in this work reveals that certain combinations of droplet volume and nanoscale topographic parameters can significantly hinder or promote wetting processes such as spreading, wicking, and imbibition.

Controlling the Outgrowth and Functions of Neural Stem Cells: The Effect of Surface Topography.

Neural stem cells (NSCs) are self-renewing cells that generate the major cell types of the central nervous system, namely neurons, astrocytes and oligodendrocytes, during embryonic development and in the adult brain. NSCs reside in a complex niche where they are exposed to a plethora of signals, including both soluble and physical signals such as compressive and shear stresses, but also discontinuities and differences in morphology of the extracellular environment, termed as topographical features. Different approaches that incorporate artificial micro- and nano-scale surface topographical features have been developed aiming to recapitulate the in vivo NSC niche discontinuities and features, particularly for in vitro studies. The present review article aims at reviewing the existing body of literature on the use of artificial micro- and nano-topographical features to control NSCs orientation and differentiation into neuronal and/or neuroglial lineage. The different approaches on the study of the underlying mechanism of the topography-guided NSC responses are additionally revised and discussed.

Effect of topography-dependent light coupling through a near-field aperture on the local photocurrent of a solar cell.

An aperture-type scanning near-field optical microscope (a-SNOM) is readily used for the optical and optoelectronic characterizations of a wide variety of chemical, biological and optoelectronic samples with sub-wavelength optical resolution. These samples mostly exhibit nanoscale topographic variations, which are related to local material inhomogeneity probed either by an optical contrast or by secondary effects such as photoconductivity or photoluminescence. To date, in the interpretation and evaluation of the measurement results from a-SNOM or derived methods, often only the local material inhomogeneity is taken into account. A possible influence of the optical interaction between the scanning probe and the surface topography is rarely discussed. In this paper, we present experimental and theoretical investigation of the effects of nanoscale topographic features on a-SNOM measurement results. We conduct local photocurrent measurements on a thin-film solar cell with an a-SNOM as the illumination source. A clear correlation between the photocurrent response and local topography is observed in all measurements with a signal contrast of up to ∼30%, although the sample features homogeneous permittivity and electrical properties. With the help of finite-difference time-domain (FDTD) simulations, this correlation is reproduced and local light coupling is identified as the mechanism which determines the local photocurrent response. Our results suggest that a-SNOM-based measurements of any sample with material inhomogeneity will be superimposed by the local light-coupling effect if surface topography variation exists. This effect should always be taken into consideration for an accurate interpretation of the measurement results.

Decreased bacterial growth on titanium nanoscale topographies created by ion beam assisted evaporation.

Titanium is one of the most widely used materials for orthopedic implants, yet it has exhibited significant complications in the short and long term, largely resulting from poor cell–material interactions. Among these many modes of failure, bacterial infection at the site of implantation has become a greater concern with the rise of antibiotic-resistant bacteria. Nanostructured surfaces have been found to prevent bacterial colonization on many surfaces, including nanotextured titanium. In many cases, specific nanoscale roughness values and resulting surface energies have been considered to be “bactericidal”; here, we explore the use of ion beam evaporation as a novel technique to create nanoscale topographical features that can reduce bacterial density. Specifically, we investigated the relationship between the roughness and titanium nanofeature shapes and sizes, in which smaller, more regularly spaced nanofeatures (specifically 40–50 nm tall peaks spaced ~0.25 μm apart) were found to have more effect than surfaces with high roughness values alone.

Nanofeatured Titanium Surfaces for Dental Implantology: Biological Effects, Biocompatibility, and Safety

Nanotechnology enables the control and modification of the chemical and topographical characteristics of materials of size less than 100 nm, down to 10 nm. The goal of this review is to discuss the role of titanium substrates as nanoscale surface modification tools for improving various aspects of implantology, including osseointegration and antibacterial properties. Techniques that can impart nanoscale topographical features to endosseous implants are described. Since the advent of nanotechnology, cellular specific functions, such as adhesion, proliferation, and differentiation, have been better understood. By applying these technologies, it is possible to direct cellular responses and improve osseointegration. Conversely, modulating surface features by nanotechnology could have the effect of decreased bacterial colonization.

Facile electrochemical synthesis of anatase nano-architectured titanium dioxide films with reversible superhydrophilic behavior

In the present work we report a facile and readily-scalable electrochemical anodization technique for preparation of superhydrophilic TiO2 films having reversible wettability properties. The electrochemically anodized Titanium (Ti) foils manifest nanoscale topographical features, interconnected nanowebs and nanofibrils, that enhance both surface roughness and light absorption. After 5 min of UV illumination a water contact angle (WCA) of 4.8° is measured for a 5 μL deionized water droplet, while after 5 min of whitelight illumination the WCA is 3.2°. Moreover, under UV illumination the superhydrophilic Ti foils exhibit self-cleaning properties. Key factors contributing to the superhydrophilic character include surface topology, and surface chemical reactions.

Directed migration of cancer cells guided by the graded texture of the underlying matrix.

Living cells and the extracellular matrix (ECM) can display complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration — which we term ‘topotaxis’ — by which cell movement is guided by the gradient of the nanoscale topographic features in the cells’ ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI3K-Akt and ROCK-MLCK. In melanoma cancer cells, this balance can be altered by different ECM inputs, pharmacological perturbations or genetic alterations, particularly a loss of PTEN in aggressive melanoma cells. We conclude that topotaxis is a product of the material properties of cells and the surrounding ECM, and propose that the invasive capacity of many cancers may depend broadly on topotactic responses, providing a potentially attractive mechanism for controlling invasive and metastatic behaviour.

Conversion of nanoscale topographical information of cluster-assembled zirconia surfaces into mechanotransductive events promotes neuronal differentiation.

BackgroundThanks to mechanotransductive components cells are competent to perceive nanoscale topographical features of their environment and to convert the immanent information into corresponding physiological responses. Due to its complex configuration, unraveling the role of the extracellular matrix is particularly challenging. Cell substrates with simplified topographical cues, fabricated by top-down micro- and nanofabrication approaches, have been useful in order to identify basic principles. However, the underlying molecular mechanisms of this conversion remain only partially understood.ResultsHere we present the results of a broad, systematic and quantitative approach aimed at understanding how the surface nanoscale information is converted into cell response providing a profound causal link between mechanotransductive events, proceeding from the cell/nanostructure interface to the nucleus. We produced nanostructured ZrO2 substrates with disordered yet controlled topographic features by the bottom-up technique supersonic cluster beam deposition, i.e. the assembling of zirconia nanoparticles from the gas phase on a flat substrate through a supersonic expansion. We used PC12 cells, a well-established model in the context of neuronal differentiation. We found that the cell/nanotopography interaction enforces a nanoscopic architecture of the adhesion regions that affects the focal adhesion dynamics and the cytoskeletal organization, which thereby modulates the general biomechanical properties by decreasing the rigidity of the cell. The mechanotransduction impacts furthermore on transcription factors relevant for neuronal differentiation (e.g. CREB), and eventually the protein expression profile. Detailed proteomic data validated the observed differentiation. In particular, the abundance of proteins that are involved in adhesome and/or cytoskeletal organization is striking, and their up- or downregulation is in line with their demonstrated functions in neuronal differentiation processes.ConclusionOur work provides a deep insight into the molecular mechanotransductive mechanisms that realize the conversion of the nanoscale topographical information of SCBD-fabricated surfaces into cellular responses, in this case neuronal differentiation. The results lay a profound cell biological foundation indicating the strong potential of these surfaces in promoting neuronal differentiation events which could be exploited for the development of prospective research and/or biomedical applications. These applications could be e.g. tools to study mechanotransductive processes, improved neural interfaces and circuits, or cell culture devices supporting neurogenic processes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0171-3) contains supplementary material, which is available to authorized users.