Low-frequency conductivity of low wear high-entropy alloys.

High-entropy alloys (HEAs) provide new research avenues for alloy combinations in the periodic table, opening numerous possibilities in novel-alloy applications. However, their electrical characteristics have been relatively underexplored. The challenge in establishing an HEA electrical conductivity model lies in the changes in electronic characteristics caused by lattice distortion and complexity of nanostructures. Here we show a low-frequency electrical conductivity model for the Nb-Mo-Ta-W HEA system. The cocktail effect is found to explain trends in electrical-conductivity changes in HEAs, while the magnitude of the reduction is understood by the calculated plasma frequency, free electron density, and measured relaxation time by terahertz spectroscopy. As a result, the refractory HEA Nb15Mo35Ta15W35 thin film exhibits both high hardness and excellent conductivity. This combination of Nb15Mo35Ta15W35 makes it suitable for applications in atomic force microscopy probe coating, significantly improving their wear resistance and atomic-scale image resolution.

Detection of live SARS-CoV-2 virus and its variants by specially designed SERS-active substrates and spectroscopic analyses.

A method using label-free surface enhanced Raman spectroscopy (SERS) based on substrate design is provided for an early detection and differentiation of spike glycoprotein mutation sites in live SARS-CoV-2 variants. Two SERS-active substrates, Au nanocavities (Au NCs) and Au NPs on porous ZrO2 (Au NPs/pZrO2), were used to identify specific peaks of A.3, Alpha, and Delta variants at different concentrations and demonstrated the ability to provide their SERS spectra with detection limits of 0.1-1.0% (or 104-5 copies/mL). Variant identification can be achieved by cross-examining reference spectra and analyzing the substrate-analyte relationship between the suitability of the analyte upon the hotspot(s) formed at high concentrations and the effective detection distance at low concentrations. Mutation sites on the S1 chain of the spike glycoprotein for each variant may be related and distinguishable. This method does not require sample preprocessing and therefore allows for fast screening, which is of high value for more comprehensive and specific studies to distinguish upcoming variants.

MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation.

The gene mutated in colorectal cancer (MCC) encodes a coiled-coil protein implicated, as its name suggests, in the pathogenesis of hereditary human colon cancer. To date, however, the contributions of MCC to intestinal homeostasis and disease remain unclear. Here, we examine the subcellular localization of MCC, both at the mRNA and protein levels, in the adult intestinal epithelium. Our findings reveal that Mcc transcripts are restricted to proliferating crypt cells, including Lgr5+ stem cells, where the Mcc protein is distinctly associated with the centrosome. Upon intestinal cellular differentiation, Mcc is redeployed to the apical domain of polarized villus cells where non-centrosomal microtubule organizing centers (ncMTOCs) are positioned. Using intestinal organoids, we show that the shuttling of the Mcc protein depends on phosphorylation by casein kinases 1δ and ε, which are critical modulators of WNT signaling. Together, our findings support a role for MCC in establishing and maintaining the cellular architecture of the intestinal epithelium as a component of both the centrosome and ncMTOC.

Synergistic surface-enhanced Raman scattering effect to distinguish live SARS-CoV-2 S pseudovirus.

The COVID-19 pandemic negatively affected the economy and health security on a global scale, causing a drastic change on lifestyle, calling a need to mitigate further transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Surface-enhanced Raman spectroscopy (SERS) has shown great potential in the sensitive and rapid detection of various molecules including viruses, through the identification of characteristic peaks of their outer membrane proteins. Accurate detection can be developed through the synergistic integration effect among SERS-active substrate, the appropriate laser wavelength, and the target analyte. In this study, gold nanocavities (Au NC) and Au nanoparticles upon ZrO2 nano-bowls (Au NPs/pZrO2) were tested and used as SERS-active substrates in detecting SARS-CoV-2 pseudovirus containing S protein as a surface capsid glycoprotein (SARS-CoV-2 S pseudovirus) and vesicular stomatitis virus G (VSV-G) pseudo-type lentivirus (VSV-G pseudovirus) to demonstrate their virus detection capability. The optimized Au NCs and Au NPs/pZrO2 substrates were then verified by examining the repetition of measurement, reproducibility, and detection limit. Due to the difference in geometry and composition of the substrates, the characteristic peak-positions of live SARS-CoV-2 S and VSV-G pseudoviruses in the obtained Raman spectra vary, which were also compared with those of inactivated ones. Based on the experimental results, SERS mechanism of each substrate to detect virus is proposed. The formation of hot spots brought by the synergistic integration effect among substrate, analyte, and laser induction may result differences in the obtained SERS spectra.

In-Situ Investigation on Nanoscopic Biomechanics of Streptococcus mutans at Low pH Citric Acid Environments Using an AFM Fluid Cell.

Streptococcus mutans (S. mutans) is widely regarded as the main cause of human dental caries via three main virulence factors: adhesion, acidogenicity, and aciduricity. Citric acid is one of the antibiotic agents that can inhibit the virulence capabilities of S. mutans. A full understanding of the acidic resistance mechanisms (ARMs) causing bacteria to thrive in citrate transport is still elusive. We propose atomic force microscopy (AFM) equipped with a fluid cell to study the S. mutans ARMs via surface nanomechanical properties at citric acid pH 3.3, 2.3, and 1.8. Among these treatments, at pH 1.8, the effect of the citric acid shock in cells is demonstrated through a significantly low number of high adhesion zones, and a noticeable reduction in adhesion forces. Consequently, this study paves the way to understand that S. mutans ARMs are associated with the variation of the number of adhesion zones on the cell surface, which is influenced by citrate and proton transport. The results are expected to be useful in developing antibiotics or drugs involving citric acid for dental plaque treatment.

Ag Nanostructures with Spikes on Adhesive Tape as a Flexible Sers-Active Substrate for In Situ Trace Detection of Pesticides on Fruit Skin.

Nanostructures with spikes (NSPs) have been a subject of several surface-enhanced Raman scattering (SERS) applications owing to their significant Raman signal enhancement brought about by the combined effects of interspike coupling and the accumulated induction on the tips of spikes. Thus, NSPs offer great potential as a SERS-active substrate for relevant applications that require a high density of enhanced "hot spots". In this study, Ag NSPs were synthesized in varying degrees of agglomeration and were thereafter deposited onto a transparent adhesive tape as a flexible substrate for SERS applications, specifically, in the detection of trace amounts of pesticides. These flexible substrates were referred to as Ag NSPs/tape and optimized with an enhancement factor (EF) of ca. 1.7 × 107. A strong resulting signal enhancement could be attributed to an optimal degree of agglomeration and, consequently, the distances among/between spikes. Long spikes on the synthesized core of Ag NSPs tend to be loosely spaced, which are suitable in detecting relatively large molecules that could access the spaces among the spikes where "hot spots" are generally formed. Since one side of the transparent tape is adhesive, the paste-and-peel off method was successful in obtaining phosmet and carbaryl residues from apple peels as reflected in the acquired SERS spectra. In situ trace detection of the pesticides at low concentrations down to 10-7 M could be demonstrated. In situ trace detection of mixed pesticides was possible as the characteristic peaks of both pesticides were observed in equimolar mixtures of the analytes at 10-2 to 10-4 M. This study is, thus, premised upon applying for in situ trace detection on e.g., fruit skin.

SERS-Active Substrate with Collective Amplification Design for Trace Analysis of Pesticides.

Health risks posed by the exposure to trace amounts of pesticide residue in agricultural products have gained a lot of concerns, due to their neurotoxic nature. The applications of surface-enhanced Raman Scattering (SERS) as a detection technique have consistently shown its potential as a rapid and sensitive means with minimal sample preparation. In this study, gold nanoparticles (Au NPs) in elliptical shapes were collected into a layer of ordered zirconia concave pores. The porous zirconia layer (pZrO2) was then deposited with Au NPs, denoted as Au NPs (x)/pZrO2, where x indicates the deposition thickness of Au NPs in nm. In the concave structure of pZrO2, Au-ZrO2 and Au-Au interactions provide a synergistic and physical mechanism of SERS, which is anticipated to collect and amplify SERS signals and thereafter improve the enhancement factor (EF) of Au NPs/pZrO2. By taking Rhodamine 6G (R6G) as the test molecule, EF of Au NPs/pZrO2 might reach to 7.0 × 107. Au NPs (3.0)/pZrO2 was then optimized and competent to detect pesticides, e.g., phosmet and carbaryl at very low concentrations, corresponding to the maximum residue limits of each, i.e., 0.3 ppm and 0.2 ppm, respectively. Au NPs (3.0)/pZrO2 also showed the effectiveness of distinguishing between phosmet and carbaryl under mixed conditions. Due to the strong affinities of the phosphoric groups and sulfur in phosmet to the Au NPs (3.0)/pZrO2, the substrate exhibited selective detection to this particular pesticide. In this study, Au NPs (3.0)/pZrO2 has thus demonstrated trace detection of residual pesticides, due to the substrate design that intended to provide collective amplification of SERS.

Micro-colonization of arsenic-resistant Staphylococcus sp. As-3 on arsenopyrite (FeAsS) drives arsenic mobilization under anoxic sub-surface mimicking conditions.

We investigated the subsurface biomatrix of the most abundant As-mineral, arsenopyrite (FeAsS), and meticulously studied a potential biogenic arsenic mobilization phenomenon. An arsenic-resistant [up to 7.5 mM As(III) and 200 mM As(V)] and arsenate-reducing bacterial strain (Staphylococcus sp. As-3) was isolated from a sediment core sample taken from the Budai borehole, on the southwestern coast of Taiwan. Isolate As-3 could reduce 5 mM As(V) to 3.04 mM in 96 h, generating 1.6 mM As(III) under anoxic conditions. Isolate As-3, which adsorbed As(V) up to 19.02 mg g-1 (cdw) and As(III) up to 0.46 mg g-1 (cdw), demonstrated effective As-bioaccumulating ability, as corroborated by a TEM-EDS analysis. Under anaerobic batch conditions, isolate As-3 micro-colonies could grow on as well as interact with arsenopyrite (FeAsS), mobilizing arsenic into soluble phase as As(III) and As(V). Using synchrotron radiation-based FTIR micro-spectroscopy, various functional group signatures and critical chemical bonds enabling a direct interaction with arsenopyrite were underpinned, such as a potential P-OFe bond involved in facilitating bacteria-mineral interaction. Using atomic force microscopy, we analyzed the scattered bacterial cell arrangement and structure and measured various biomechanical properties of micro-colonized Staphylococcus sp. As-3 cells on arsenopyrite. We suggest that the release of organic acids from As-3 drives soluble arsenic release in the aqueous phase under anoxic conditions through oxidative dissolution. Furthermore, arsC-encoding putative cytoplasmic arsenic reductase sequencing and transcript characterization indicated that arsC plays a possible role in the reduction of moderately soluble As(V) to highly soluble toxic As(III) under anoxic conditions. Thus, we suggest that firmicutes such as Staphylococcus sp. As-3 may play an important role in microbially-mediated arsenic mobilization, leading to arsenic release in the sub-surface niche.

Strontium Oxide Deposited onto a Load-Bearable and Porous Titanium Matrix as Dynamic and High-Surface-Contact-Area Catalysis for Transesterification.

Strontium oxide (SrO) deposited onto a porous titanium (Ti)-based scaffold (P-Ti) is a promising and novel approach for high-throughput transesterification. Notably, a highly porous and calcinated scaffold provides a load-bearable support for a continuous process, while the calcinated SrO catalyst, as it is well distributed inside the porous matrix, can extend its surface contact area with the reactant. In this work, the formation of transesterification reaction with the conversion and production of olive oil to biodiesel inside the porous matrix is particularly examined. The as-designed SrO-coated porous titanium (Ti)-based scaffold with 55% porosity was prepared via a hydrothermal procedure, followed by a dip coating method. Mechanical tests of samples were conducted by a nanoindentator, whereas the physical and chemical structures were identified by IR and Raman Spectroscopies. The results implied that SrO catalysts can be firmly deposited onto a load-bearable, highly porous matrix and play an effective role for the transesterification reaction with the oil mass. It is promising to be employed as a load-bearable support for a continuous transesterification process, such as a process for batch or continuous biodiesel production, under an efficient heating source by a focused microwave system.

Gold Nanoparticle-Coated ZrO2-Nanofiber Surface as a SERS-Active Substrate for Trace Detection of Pesticide Residue.

Trace detection of common pesticide residue is necessary to assure safety of fruit and vegetables, given that the potential health risk to consumers is attributed to the contamination of the sources. A simple, rapid and effective means of finding the residue is however required for household purposes. In recent years, the technique in association with surface-enhanced Raman scattering (SERS) has been well developed in particular for trace detection of target molecules. Herein, gold nanoparticles (Au NPs) were integrated with sol-gel spin-coated Zirconia nanofibers (ZrO2 NFs) as a chemically stable substrate and used for SERS application. The morphologies of Au NPs/ZrO2 NFs were adjusted by the precursor concentrations (_X, X = 0.05⁻0.5 M) and the effect of SERS on Au NPs/ZrO2 NFs_X was evaluated by different Raman laser wavelengths using rhodamine 6G as the probe molecule at low concentrations. The target pesticides, phosmet (P1), carbaryl (C1), permethrin (P2) and cypermethrin (C2) were thereafter tested and analyzed. Au NPs/ZrO2 NFs_0.3 exhibited an enhancement factor of 2.1 × 107, which could detect P1, C1, P2 and C2 at the concentrations down to 10-8, 10-7, 10-7 and 10-6 M, respectively. High selectivity to the organophosphates was also found. As the pesticides were dip-coated on an apple and then measured on the diluted juice containing sliced apple peels, the characteristic peaks of each pesticide could be clearly identified. It is thus promising to use NPs/ZrO2 NFs_0.3 as a novel SERS-active substrate for trace detection of pesticide residue upon, for example, fruits or vegetables.

Identification of Characteristic Macromolecules of Escherichia coli Genotypes by Atomic Force Microscope Nanoscale Mechanical Mapping.

The categorization of microbial strains is conventionally based on the molecular method, and seldom are the morphological characteristics in the bacterial strains studied. In this research, we revealed the macromolecular structures of the bacterial surface via AFM mechanical mapping, whose resolution was not only determined by the nanoscale tip size but also the mechanical properties of the specimen. This technique enabled the nanoscale study of membranous structures of microbial strains with simple specimen preparation and flexible working environments, which overcame the multiple restrictions in electron microscopy and label-enable biochemical analytical methods. The characteristic macromolecules located among cellular surface were considered as surface layer proteins and were found to be specific to the Escherichia coli genotypes, from which the averaged molecular sizes were characterized with diameters ranging from 38 to 66 nm, and the molecular shapes were kidney-like or round. In conclusion, the surface macromolecular structures have unique characteristics that link to the E. coli genotype, which suggests that the genomic effects on cellular morphologies can be rapidly identified using AFM mechanical mapping. Graphical Abstract Quantification of surface macromolecules of E. coli cells using AFM mechanical mapping. Surface macromolecules of cellular surface of three E. coli genotypes, MG1655, CFT073, and RS218, were characterized with the sizes ranging from 38 to 66 nm and with round or kidney-like shapes. The topography images were colored with adhesion mapping with the scale bars = 200 nm.

Ageing, Shocks and Wear Mechanisms in ZTA and the Long-Term Performance of Hip Joint Materials.

The surface morphologies and microstructures of Zirconia Toughened Alumina (ZTA) femoral heads were analyzed following in vitro tests aiming to simulate in vivo degradation. Three phenomena potentially leading to degradation were investigated: shocks, friction and hydrothermal ageing. Shocks due to micro-separation created the main damage with the formation of wear stripes on the femoral head surfaces. Atomic Force Microscopy (AFM) images suggested the release of wear debris of various shapes and sizes through inter- and intra-granular cracks; some debris may have a size lower than 100 nm. A decrease in hardness and Young's modulus was measured within the wear stripes by nanoindentation technique and was attributed to the presence of surface and sub-surface micro-cracks. Such micro-cracks mechanically triggered the zirconia phase transformation in those worn areas, which in return presumably reduced further crack propagation. In comparison with shocks, friction caused little wear degradation as observed from AFM images by scarce pullout of grains. The long-term resistance of the ZTA composite material against hydrothermal ageing is confirmed by the present observations.

Hydrothermal Fabrication of Highly Porous Titanium Bio-Scaffold with a Load-Bearable Property.

Porous titanium (P_Ti) is considered as an effective material for bone scaffold to achieve a stiffness reduction. Herein, biomimetic (bio-)scaffolds were made of sintered P_Ti, which used NaCl as the space holder and had it removed via the hydrothermal method. X-ray diffraction results showed that the subsequent sintering temperature of 1000 °C was the optimized temperature for preparing P_Ti. The compressive strength of P_Ti was measured using a compression test, which revealed an excellent load-bearing ability of above 70 MPa for that with an addition of 50 wt % NaCl (P_Ti_50). The nano-hardness of P_Ti, tested upon their solid surface, was presumably consistent with the density of pores vis-à-vis the addition of NaCl. Overall, a load-bearable P_Ti with a highly porous structure (e.g., P_Ti_50 with a porosity of 43.91% and a pore size around 340 µm) and considerable compressive strength could be obtained through the current process. Cell proliferation (MTS) and lactate dehydrogenase (LDH) assays showed that all P_Ti samples exhibited high cell affinity and low cell mortality, indicating good biocompatibility. Among them, P_Ti_50 showed relatively good in-cell morphology and viability, and is thus promising as a load-bearable bio-scaffold.

Classification and Lineage Tracing of SH2 Domains Throughout Eukaryotes.

Today there exists a rapidly expanding number of sequenced genomes. Cataloging protein interaction domains such as the Src Homology 2 (SH2) domain across these various genomes can be accomplished with ease due to existing algorithms and predictions models. An evolutionary analysis of SH2 domains provides a step towards understanding how SH2 proteins integrated with existing signaling networks to position phosphotyrosine signaling as a crucial driver of robust cellular communication networks in metazoans. However organizing and tracing SH2 domain across organisms and understanding their evolutionary trajectory remains a challenge. This chapter describes several methodologies towards analyzing the evolutionary trajectory of SH2 domains including a global SH2 domain classification system, which facilitates annotation of new SH2 sequences essential for tracing the lineage of SH2 domains throughout eukaryote evolution. This classification utilizes a combination of sequence homology, protein domain architecture and the boundary positions between introns and exons within the SH2 domain or genes encoding these domains. Discrete SH2 families can then be traced across various genomes to provide insight into its origins. Furthermore, additional methods for examining potential mechanisms for divergence of SH2 domains from structural changes to alterations in the protein domain content and genome duplication will be discussed. Therefore a better understanding of SH2 domain evolution may enhance our insight into the emergence of phosphotyrosine signaling and the expansion of protein interaction domains.

Expression and Production of SH2 Domain Proteins.

The Src Homology 2 (SH2) domain lies at the heart of phosphotyrosine signaling, coordinating signaling events downstream of receptor tyrosine kinases (RTKs), adaptors, and scaffolds. Over a hundred SH2 domains are present in mammals, each having a unique specificity which determines its interactions with multiple binding partners. One of the essential tools necessary for studying and determining the role of SH2 domains in phosphotyrosine signaling is a set of soluble recombinant SH2 proteins. Here we describe methods, based on a broad experience with purification of all SH2 domains, for the production of SH2 domain proteins needed for proteomic and biochemical-based studies such as peptide arrays, mass-spectrometry, protein microarrays, reverse-phase microarrays, and high-throughput fluorescence polarization (HTP-FP). We describe stepwise protocols for expression and purification of SH2 domains using GST or poly His-tags, two widely adopted affinity tags. In addition, we address alternative approaches, challenges, and validation studies for assessing protein quality and provide general characteristics of purified human SH2 domains.

Introduction: History of SH2 Domains and Their Applications.

The Src Homology 2 (SH2) domain is the prototypical protein interaction module that lies at the heart of phosphotyrosine signaling. Since its serendipitous discovery, there has been a tremendous advancement in technologies and an array of techniques available for studying SH2 domains and phosphotyrosine signaling. In this chapter, we provide a glimpse of the history of SH2 domains and describe many of the tools and techniques that have been developed along the way and discuss future directions for SH2 domain studies. We highlight the gist of each chapter in this volume in the context of: the structural biology and phosphotyrosine binding; characterizing SH2 specificity and generating prediction models; systems biology and proteomics; SH2 domains in signal transduction; and SH2 domains in disease, diagnostics, and therapeutics. Many of the individual chapters provide an in-depth approach that will allow scientists to interrogate the function and role of SH2 domains.

Characterizing SH2 Domain Specificity and Network Interactions Using SPOT Peptide Arrays.

Src Homology 2 (SH2) domains are protein interaction modules that recognize and bind tyrosine phosphorylated ligands. Their ability to distinguish binding to over thousands of potential phosphotyrosine (pTyr) ligands within the cell is critical for the fidelity of receptor tyrosine kinase (RTK) signaling. Within humans there are over a hundred SH2 domains with more than several thousand potential ligands across many cell types and cell states. Therefore, defining the specificity of individual SH2 domains is critical for predicting and identifying their physiological ligands. Here, in this chapter, I describe the broad use of SPOT peptide arrays for examining SH2 domain specificity. An orientated peptide array library (OPAL) approach can uncover both favorable and non-favorable residues, thus providing an in-depth analysis to SH2 specificity. Moreover, I discuss the application of SPOT arrays for paneling SH2 ligand binding with physiological peptides.

Binding Assays Using Recombinant SH2 Domains: Far-Western, Pull-Down, and Fluorescence Polarization.

Recognition of phosphotyrosine-containing sequences by SH2 domains confers specificity in tyrosine kinase pathways. By assessing interactions between isolated SH2 domains and their binding proteins, it is possible to gain insight into otherwise inaccessible complex cellular systems. Far-Western, pull-down, and fluorescence polarization (FP) have been frequently used for characterization of phosphotyrosine signaling. Here, we outline standard protocols for these established assays using recombinant SH2 domain, emphasizing the importance of appropriate sample preparation and assay controls.

In-situ, time-lapse study of extracellular polymeric substance discharge in Streptococcus mutans biofilm.

Streptococcus mutans is one of the main pathogens that cause tooth decay. By metabolizing carbohydrates, S. mutans emits extracellular polymeric substance (EPS) that adheres to the tooth surface and forms layers of biofilm. Periodontal disease occurs due to the low pH environment created by S. mutans biofilm, and such an acidic environment gradually erodes tooth enamel. Since the existence of EPS is essential in the formation of biofilm, the in-situ investigation of its generation and distribution in real time is the key to the control and suppression of S. mutans biofilm. Prior studies of the biofilm formation process by fluorescence microscope, scanning electron microscope, or spectroscope have roughly divided the mechanism into three stages: (1) initial attachment; (2) microcolonies; and (3) maturation. However, these analytical methods are incapable to observe real-time changes in different locations of the extracellular matrix, and to analyze mechanical properties for single bacteria in micro and nanoscale. Since atomic force microscopy (AFM) operates by precise control of tip-sample interaction forces in liquid and in air, living microorganisms can be analyzed under near-physiological conditions. Thus, analytical techniques based on AFM constitute powerful tools for the study of biological samples, both qualitatively and quantitatively. In this study, we used AFM to quantitatively track the changes of multiple nanomechanical properties of S. mutans, including dissipation energy, adhesion force, deformation, and elastic modulus at different metabolic stages. The data revealed that the bacterial extracellular matrix has a gradient distribution in stickiness, in which different stickiness indicates the variation of EPS compositions, freshness, and metabolic stages. In-situ, time-lapse AFM images showed the local generation and distribution of EPS at different times, in which the highest adhesion distributed along sides of the S. mutans cells. Through time-lapse analysis, we concluded that each contour layer is associated with a dynamic process of cell growth and nutrient consumption, and S. mutans is capable of controlling the priority of EPS secretion at specific locations. The live bacteria exhibited cyclic metabolic activities in the period of 23-34min at the maturation stage of biofilm formation. In addition, the discharge of EPS is responsive to the shear stress caused by the topographical change of biofilm to provide stronger mechanical support in the formation of 3D networked biofilm.

Probed adhesion force of living lung cells with a tip-modified atomic force microscope.

The mechanical properties of the extracellular matrix play an important role in bio-microenvironment activities. Herein, atomic force microscope (AFM) was used to measure the interaction between Au and Ag nanoparticle (NP) clusters on the surface of human fetal lung cells. Using (3-mercapto-propyl) triethoxysilane (MPTMS), NP clusters were grafted onto the apex of AFM tip, and then, the adhesion force between the tip and the cell was analyzed. The measured adhesion force increased from 92 pN for AFM tip to 332 pN for that modified with MPTMS. The increase is most probably contributed by the nonspecific interactions between the apex of the modified AFM tip and the surface of the cells. The adhesion forces between the surface of NPs clusters grafted AFM tip and that of lung cells were dramatically reduced as NPs clusters were replaced by MPTMS. For the former, as the Au NPs cluster was applied, the adhesion force reached to 122 pN, whereas it significantly augmented with the addition of the cluster's size and dimension on the AFM tip. For the case of Ag cluster grafted on AFM tip, its adhesion force with the surface of the cells significantly lowered and reduced to 56 pN. Presumably, the electrostatic or van der Waals force between the two surfaces results in the variation of measurements. It is also very likely that the cell-surface interactions are probably varied by the nature of the contact surfaces, like the force-distance of attraction. The result is significant for understanding the the nature of the interactions between the surface of NPs and the membrane of lung cells.