Ability Of Atomic Force Microscopy Research Articles

Self-assembled peptide nanoparticles for photodynamic therapy: morphological and mechanical effects on hepatocellular carcinoma cells

Self-assembling peptides, offering favorable biocompatibility, high stability, and easy incorporation of various functionalities, have demonstrated enormous potential for the precise design of next-generation nanodrugs for non-invasive tumor therapy. Peptide-based supramolecular photodynamic therapy (PDT) has shown great promise as an emerging modality for cancer treatment, achieving substantially-enhanced photosensitizer delivery selectivity and treatment efficacy, based on peptide biological activity and self-assembly potential. Although considerable research has been conducted toward fabricating self-assembling peptide-based smart nanodrugs for PDT, few studies have investigated cellular biophysical responses as indicators of tumor function and metabolic state. Here, via atomic force microscopy (AFM)-based morphological and mechanical measurements, including optical microscopy and scanning electron microscopy, we observed, for the first time, variation in membrane stiffness of human liver (HepG2) cancer cells treated with self-assembling peptides serving as a PDT nanodrug. This biophysical information will help to establish a comprehensive understanding of the anticancer effect of peptide-based smart nanodrugs, and highlight the exceptional ability of AFM in determining cell-surface properties.

Pore structure and heterogeneity of shale gas reservoirs and its effect on gas storage capacity in the Qiongzhusi Formation

Fine characterization of pore systems and heterogeneity of shale reservoirs are significant contents of shale gas reservoir physical property research. The research on micro-control factors of low productivity in the Qiongzhusi Formation (Fm.) is still controversial. The lower Cambrian Qiongzhusi Fm. in the Qujing, Yunnan was taken as the object to investigate the influence of mineral compositions on the physical properties of the reservoir and the heterogeneity of shale, using the algorithm to improve the characterization ability of Atomic Force Microscopy (AFM). The results showed that: (1) The pores are mainly wedge-shaped pores and V-shaped pores. The pore diameter of the main pore segment ranges from 5 to 10 nm. Mesopores are mainly developed in the Qiongzhusi Fm. shale in Well QD1, with the average pore diameter of 6.08 nm. (2) Microscopic pore structure and shale surface properties show strong heterogeneity, which complicates the micro-migration of shale gas and increases the difficulty of identifying high-quality reservoirs. (3) The increase of clay mineral content intensifies the compaction and then destroys the pores. Conversely, brittle minerals can protect pores. The support and protection of brittle minerals to pores space depend on their content, mechanical properties and diagenesis. (4) Compression damage to pores, large microscopic roughness and surface fluctuations and strong pore structure heterogeneity are the reasons for the poor gas storage capacity of the Qiongzhusi Fm., which will lead to poor productivity in the Qiongzhusi Fm.

Number density distribution of solvent molecules on a substrate: a transform theory for atomic force microscopy.

Atomic force microscopy (AFM) in liquids can measure a force curve between a probe and a buried substrate. The shape of the measured force curve is related to hydration structure on the substrate. However, until now, there has been no practical theory that can transform the force curve into the hydration structure, because treatment of the liquid confined between the probe and the substrate is a difficult problem. Here, we propose a robust and practical transform theory, which can generate the number density distribution of solvent molecules on a substrate from the force curve. As an example, we analyzed a force curve measured by using our high-resolution AFM with a newly fabricated ultrashort cantilever. It is demonstrated that the hydration structure on muscovite mica (001) surface can be reproduced from the force curve by using the transform theory. The transform theory will enhance AFM's ability and support structural analyses of solid/liquid interfaces. By using the transform theory, the effective diameter of a real probe apex is also obtained. This result will be important for designing a model probe of molecular scale simulations.

Probing the stiffness of isolated nucleoli by atomic force microscopy

In eukaryotic cells, ribosome biogenesis occurs in the nucleolus, a membraneless nuclear compartment. Noticeably, the nucleolus is also involved in several nuclear functions, such as cell cycle regulation, non-ribosomal ribonucleoprotein complex assembly, aggresome formation and some virus assembly. The most intriguing question about the nucleolus is how such dynamics processes can occur in such a compact compartment. We hypothesized that its structure may be rather flexible. To investigate this, we used atomic force microscopy (AFM) on isolated nucleoli. Surface topography imaging revealed the beaded structure of the nucleolar surface. With the AFM's ability to measure forces, we were able to determine the stiffness of isolated nucleoli. We could establish that the nucleolar stiffness varies upon drastic morphological changes induced by transcription and proteasome inhibition. Furthermore, upon ribosomal proteins and LaminB1 knockdowns, the nucleolar stiffness was increased. This led us to propose a model where the nucleolus has steady-state stiffness dependent on ribosome biogenesis activity and requires LaminB1 for its flexibility.

Nanomechanical properties of pure and doped Ta2O5 and the effect of microwave irradiation

The nanomechanical properties of pure and doped Ta2O5 films (100 nm) on Si, and the effect of short time (10 s) microwave irradiation are studied by nanoindentation testing. The local mechanical parameters as determined by the force measuring ability of atomic force microscopy are compared with the data from both the Oliver–Pharr nanoindentation technique and the continuous stiffness measurements. The impact of the dopant type (Hf and Al) on the surface morphology, elastic modulus and hardness of the films is determined. The results reveal an increase in elastic modulus and hardness after the doping. The irradiation produces a little lower values of mechanical parameters. The results are discussed in juxtaposition with the established previously strong effect of irradiation on the electrical properties of Ta2O5-based stacks. From device perspective point of view Hf-doped Ta2O5 is noteworthy for micro-electro-mechanical system applications.

AFM in Advanced Pharmaceutical Technology

The necessity for development of new drug delivery systems for poorly soluble drugs and therapeutics which targets directly the pathogenic area requires the design of complex systems in nanoscale. Atomic Force Microscopy (AFM) since its discovery offers a unique tool to develop novel drug delivery systems. Its capability to investigate, characterise surfaces and measure forces with spatial resolution at nano-scale respectively contributes to develop and analyse pharmaceutical systems and biomedical devices with complex structures and chemistries. Specifically, polymeric nanoparticles and liposomal drug formulation have been studied extensively by using AFM where their size and morphology where revealed [1]. However, apart from topographical information, AFM can provide details on the local compositions of the sample. There are many modes that can be used to achieve this but the most common is to monitor the phase shift of the oscillating cantilever in tapping mode Such ‘Phase imaging’ can be used to detect nanoscale variation in composition, adhesion, friction, viscoelasticity, and other properties of the materials. Changes in the phase lag often indicate changes in the properties of the sample surface. Phase imaging has proved an extremely useful tool for pharmaceutical characterization. Phase imaging has been used to reveal polymeric forms from single crystal measurements [2] to confirm phase separation of two copolymers for drug delivery [3], to establish the stability of the formulation on different environments [4] and to identify formation of amorphous domains during milling of crystalline salbutamol [5]. Moreover, the ability of AFM to operate on different conditions of temperature humidity and in liquid allows studying the kinetics of range of phenomena. An interesting work was published from Miyazaki et al. where the crystal growth rate of Nifedipine, dispersed in PEG polymer matrix, was quantified [6]. Also, the dissolution process of aspirin on different facets of the crystal was studied by Danesh et al . showing their differences in dissolution rate [7]. The ability of AFM to measure force measurements have been used to investigate interactions among the different compounds in the formulation. To achieve this, the AFM cantilever is modified by attaching a particle directly onto the probe tip and is brought in contact with the substrate of interest, the force required to separate them is the measure of their adhesion. This application of AFM has been used extensively to aerosol drug formulation where the API is associated with a carrier which is released in the site of actions. For instance, AFM has been used to investigate the adhesion force of salbutamol with different excipients [8]. Moreover, localised surface energy and young’s modulus of various compounds have been measured. For example, Young’s modulus were derived from both PLA and PLA/everolimus directly from stent surface on different temperatures. The results showed that everolimus does not affect the mechanical properties of PLA up to 1/1 (w/w) drug loading of the mixture. Also, a significant drop of the Young’s modulus in solution was observed at 36°C, suggests that in vivo the Tg of the polymer is below body temperature [9]. Furthermore, force measurements have been used to identify the encapsulation the efficiency of liposomes as the rigidity of encapsulating liposomes is higher [10].

Bulk phase separation study by atomic force microscope friction imaging of natural rubber/poly(methyl methacrylate) film

The first observation of bulk phase separation in immiscible natural rubber (NR)/poly(methyl methacrylate) (PMMA) film using atomic force microscopy (AFM) is reported. Three different forms of AFM measurements: topographic, friction force imaging, and nanoindentation have been effectively used to investigate combined morphological and compositional mapping of the NR/PMMA system. The fracture temperature during sample microtoming and material physical properties could be responsible for the observed topographic contrast. The stronger contrast of friction imaging, relative to topographic imaging, is ascribed to local variations in mechanical properties of the phase-separated domains. Friction force imaging associated with nanoindentation response, performed under AFM force mode, highlights the AFM's ability for probing local friction, adhesion, and elastic properties, and for compositional mapping of heterogeneous polymer film. The resulting friction force imaging along with the response of the nanoindentation are in good agreement, indicating that PMMA exists mainly near the modified NR surface.

Gold nanoparticle aggregation-based highly sensitive DNA detection using atomic force microscopy

The potential ability of atomic force microscopy (AFM) as a quantitative bioanalysis tool is demonstrated by using gold nanoparticles as a size enhancer in a DNA hybridization reaction. Two sets of probe DNA were functionalized on gold nanoparticles and sandwich hybridization occurred between two probe DNAs and target DNA, resulting in aggregation of the nanoparticles. At high concentrations of target DNA in the range from 100 nM to 10 microM, the aggregation of gold nanoparticles was determined by monitoring the color change with UV-vis spectroscopy. The absorption spectra broadened after the exposure of DNA-gold nanoparticles to target DNA and a new absorption band at wavelengths >600 nm was observed. However, no differences were observed in the absorption spectra of the gold nanoparticles at low concentrations of target DNA (10 pM to 10 nM) due to insufficient aggregation. AFM was used as a biosensing tool over this range of target DNA concentrations in order to monitor the aggregation of gold nanoparticles and to quantify the concentration of target DNA. Based on the AFM images, we successfully evaluated particle number and size at low concentrations of target DNA. The calibration curve obtained when mean particle aggregate diameter was plotted against concentration of target DNA showed good linearity over the range 10 pM to 10 nM, the working range for quantitative target DNA analysis. This AFM-based DNA detection technique was three orders of magnitude more sensitive than a DNA detection method based on UV-vis spectroscopy.

Quantitative measurement of short-range chemical bonding forces.

We report direct force measurements of the formation of a chemical bond. The experiments were performed using a low-temperature atomic force microscope, a silicon tip, and a silicon (111) 7x7 surface. The measured site-dependent attractive short-range force, which attains a maximum value of 2.1 nanonewtons, is in good agreement with first-principles calculations of an incipient covalent bond in an analogous model system. The resolution was sufficient to distinguish differences in the interaction potential between inequivalent adatoms, demonstrating the ability of atomic force microscopy to provide quantitative, atomic-scale information on surface chemical reactivity.

Formation of Supported Phospholipid Bilayers from Unilamellar Vesicles Investigated by Atomic Force Microscopy

Since their introduction through the work of McConnell et al. in the early 80s, supported phospholipid bilayers (SPBs) have proven to be a versatile model system for investigating a wide variety of phenomena. Despite their continuous application in fundamental as well as applied research fields, the mechanism by which SPBs are formed from suspensions of unilamellar vesicles remains poorly understood. Utilizing the ability of atomic force microscopy (AFM) to investigate processes in situ and in real time, we have studied the early stages of SPB formation on mica. Unilamellar vesicles of various sizes, composed of zwitterionic phospholipids, were prepared by sonication or extrusion. Vesicles of all sizes investigated were found to adsorb to mica. Unruptured vesicles forming supported vesicular layers (SVLs), as well as disks, formed as a result of vesicle rupture, could be visualized by AFM. The behavior of the SVLs was found to depend on the vesicle size, the lipid concentration, and the presence or absence of Ca2+. The picture of the mechanism of SPB formation, which emerges from the results presented in this report, is critically compared with theoretical predictions and experimental results reported to date.