Study on degranulation of mast cells under C48/80 treatment by electroporation-assisted and ultrasound-assisted surface-enhanced Raman spectrascopy.

Both electroporation-assisted and ultrasound-assisted delivery methods can rapidly deliver nanoparticles into living cells for surface-enhanced Raman scattering (SERS) detection, but these two methods have never been compared. In this study, electroporation-assisted SERS and ultrasound-assisted SERS were employed to detect the biochemical changes of degranulated mast cells induced by mast cell stimulator (C48/80). The results showed that the cell damage of electroporation based on controllable electric pulse was smaller than that of ultrasound based on cavitation. Transmission electron microscope images of cells indicated that the nanoparticles delivered by electroporation were mainly distributed in the cytoplasm, while ultrasound could transport nanoparticles to the cytoplasm and nucleus. Therefore, electroporation-assisted SERS mainly detects the biochemical information of cytoplasm, while ultrasound-assisted SERS gets more spectral signals of nucleic acid. Both methods can obtain high quality SERS signal of cells. With drug treatment, the SERS peak intensity of 733 cm-1 attributed to phosphatidylserine decreased significantly, which may be due to the activation of mast cell degranulation pathway stimulated by C48/80 agonist, resulting in a large amount of intracellular serine being used to synthesize tryptase, while the production of phosphatidylserine decreased. Further, based on principal component analysis and linear discriminant analysis (PCA-LDA approach), ultrasound-assisted SERS could achieve better sensitivity, specificity and accuracy in the discrimination and identification of drug-treated degranulated mast cells than electroporation assisted SERS. This exploratory work is helpful to realize the real-time dynamic SERS detection of intracellular biochemical components, and it also has great potential in intracellular SERS analysis, such as the cytotoxicity assay of anti-tumor drugs or cancer cell screening.

Label-free surface enhanced Raman spectroscopy analysis of blood serum via coffee ring effect for accurate diagnosis of cancers.

Surface-enhanced Raman spectroscopy (SERS) is considered as an ultrasensitive, non-invasive as well as rapid detection technology for cancer diagnosis. In this study, we developed a novel blood serum analysis strategy using coffee ring effect-assisted label-free SERS for different types of cancer screening. Additionally, the pretreated Ag nanoparticles (Ag NPs) were mixed with the serum from liver cancer patients (n = 40), prostate cancer patients (n = 32) and healthy volunteers (n = 30) for SERS measurement. The droplets of Ag NPs-serum mixture formed the coffee ring on the peripheral after air-drying, and thus extremely enhancing Raman signal and ensuring the stability and reliability of SERS detection. Partial least square (PLS) and support vector machine (SVM) algorithms were utilized to establish the diagnosis model for SERS spectra data classifying, yielding the high diagnostic accuracy of 98.04% for normal group and two types of cancers simultaneously distinguishing. More importantly, for the unknown testing set, an ideal diagnostic accuracy of 100% could be achieved by PLS-SVM algorithm for differentiating cancers from the normal group. The results from this exploratory work demonstrate that serum SERS detection combined with PLS-SVM diagnostic algorithm and coffee ring effect has great potential for the noninvasive and label-free detection of cancer.

Label-free determination of liver cancer stages using surface-enhanced Raman scattering coupled with preferential adsorption of hydroxyapatite microspheres.

Here, we explored a label-free albumin targeted analysis method by utilizing hydroxyapatite (HAp) to adsorb-release serum albumin, in conjunction with surface-enhanced Raman scattering (SERS) for screening liver cancer (LC) at different tumor (T) stages. Excitingly, albumin can be preferentially adsorbed by HAp as compared with other serum proteins. Moreover, we developed a novel strategy using a high concentration of PO43- solution as the albumin-release agent. This method overcomes the shortcomings of the traditional purification technology of serum albumin, which requires acid to release protein, and ensures that the structure and properties of albumin are not damaged. The SERS spectra of serum albumin obtained from three sample groups were analyzed to verify the feasibility of this new method: healthy volunteers (n = 35), LC patients with T1 stage (n = 25) and LC patients with T2-T4 stage (n = 23). Furthermore, principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to classify the early T (T1) stage LC vs. normal group and advanced T (T2-T4) stage LC vs. normal group, yielding high diagnostic accuracies of 90.00% and 96.55%, respectively, which showed a 10% improvement in diagnostic accuracy for the early stage detection of cancer as compared with previous studies. The results of this exploratory work demonstrated that HAp-adsorbed-released serum albumin combined with SERS analysis has great potential for label-free, noninvasive and sensitive detection of different T stages of liver cancer.

Label-free diagnosis of breast cancer based on serum protein purification assisted surface-enhanced Raman spectroscopy.

Serum protein is generally used to assess the severity of disease, as well as cancer progression and prognosis. Herein, a simple and rapid serum proteins analysis method combined with surface-enhanced Raman spectroscopy (SERS) technology was applied for breast cancer detection. The cellulose acetate membrane (CA) was employed to extract human serum proteins from 30 breast cancer patients and 45 healthy volunteers and then extracted proteins were mixed with silver nanoparticles for SERS measurement. Additionally, we also mainly assessed the use of different ratios of proteins-silver nanoparticles (Ag NPs) mixture to generate maximum SERS signal for clinical samples detection. Two multivariate statistical analyses, principal component analysis-linear discriminate analysis (PCA-LDA) and partial least square-support vector machines (PLS-SVM) were used to analyze the obtained serum protein SERS spectra and establish the diagnostic model. The results demonstrate that the PLS-SVM model provides superior performance in the classification of breast cancer diagnosis compared with PCA-LDA. This exploratory work demonstrates that the label-free SERS analysis technique combined with CA membrane purified serum proteins has great potential for breast cancer diagnosis.

High spatio-temporal resolution measurement of A1 R and A2A R interactions combined with Iem-spFRET and E-FRET methods.

A1 R-A2A R heterodimers regulate striatal glutamatergic neurotransmission. However, few researches about kinetics have been reported. Here, we combined Iem-spFRET and E-FRET to investigate the kinetics of A1 R and A2A R interaction. Iem-spFRET obtains the energy transfer efficiency of the whole cell. E-FRET gets energy transfer efficiency with high spatial resolution, whereas, it was prone to biases because background was easily selected due to manual operation. To study the interaction with high spatio-temporal resolution, Iem-spFRET was used to correct the deviation of E-FRET. In this paper, A1 R and A2A R interaction was monitored, and the changes of FRET efficiency of the whole or/and partial cell membrane were described. The results showed that activation of A1 R or A2A R leads to rapid aggregation, inhibition of A1 R or A2A R leads to slow segregation, and the interaction is reversible. These results demonstrated that combination of Iem-spFRET and E-FRET could measure A1 R and A2A R interaction with high spatio-temporal resolution.

A microsphere nanoparticle based-serum albumin targeted adsorption coupled with surface-enhanced Raman scattering for breast cancer detection.

The serum albumin level is inseparable associated with survival in patients with breast cancer, and simultaneously serve as a good indicator of prognosis of cancer. Here, we proposed a novel extraction-isolation analysis method of albumin for breast cancer detection utilizing hydroxyapatite particles (HAp) to targeted adsorb albumin from serum relying on its specific adsorption capacity. An ideal protein-release reagent was used for isolating albumin from the surface of HAp, and meanwhile ensuring that the structure and property of albumin was not suffered damage. The surface-enhanced Raman scattering (SERS) signal of extracted albumin was obtained, and partial least squares (PLS) and linear discriminant analysis (LDA) analysis approach were employed to analyze SERS spectra data, with the aim to assess the capability of HAp method for identifying breast cancer, yielding an ideal diagnostic accuracy of 98.6%, demonstrating promising potential as a non-invasive and sensitive nanotechnology for breast cancer screening.

In vivo and in vitro study of co-expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma / Estudo in vivo e in vitro da coexpressão de LMP1 e Cripto-1 em carcinoma nasofaríngeo

Abstract Introduction: Nasopharyngeal carcinoma, an epithelial-derived malignant tumor which because of its anatomical location and atypical early symptoms, when diagnosed invasion and metastasis often have occurred. This requires a better understanding of the development mechanism, identifying diagnostic markers, and developing new treatment strategies. Objective: To study the relationship of LMP1 and Cripto-1 in nasopharyngeal carcinoma. Methods: The expression of LMP1 and Cripto-1 in specimens obtained from nasopharyngeal carcinoma patients (n = 42) and nasopharyngitis patients (n = 22) were examined. The expression of LMP1 and Cripto-1 in LMP1-negative and LMP1-positive (CNE1-LMP1) cells were also examined. Results: The expression of LMP1 and Cripto-1 was significantly higher in nasopharyngeal carcinoma than in nasopharyngitis (p < 0.05). Their expression in nasopharyngeal carcinoma with metastasis were significantly higher than that without metastasis (p < 0.05), which was correlated with TNM staging (p < 0.05). High Cripto-1 expression and high proliferation rate were seen in CNE1-LMP1 cells. Conclusions: The expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma is positively related. Their co-expression might contribute to the proliferation and metastasis of nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo é um tumor maligno derivado do epitélio de localização anatômica recôndita e sintomas iniciais atípicos; quando diagnosticado, frequentemente invasão e metástases já ocorreram. Isso requer uma melhor compreensão do seu mecanismo de desenvolvimento, identificação dos marcadores diagnósticos e desenvolvimento de novas estratégias de tratamento. Objetivo: Estudar a relação de LMP1 e Cripto-1 no carcinoma nasofaríngeo. Método: A expressão de LMP1 e Cripto-1 em espécimes obtidos de pacientes com carcinoma de nasofaringe (n = 42) e pacientes com nasofaringite (n = 22) foi analisada. A expressão de LMP1 e Cripto-1 em células LMP1-negativas e LMP1-positivas (CNE1-LMP1) também foi analisada. Resultados: A expressão de LMP1 e Cripto-1 foi significantemente maior na presença de carcinoma nasofaríngeo do que na nasofaringite (p < 0,05). Sua expressão em carcinomas com metástase foi significantemente maior do que em casos sem metástase (p < 0,05), o que se correlacionou com o estadiamento TNM (p < 0,05). Uma alta expressão de Cripto-1 e alta taxa de proliferação foram observadas nas células CNE1-LMP1. Conclusões: A expressão de LMP1 e Cripto-1 é positivamente relacionada com carcinoma nasofaríngeo. Sua coexpressão pode ser atribuída à proliferação e metástase do tumor.

Surface-enhanced Raman scattering analysis of serum albumin via adsorption-exfoliation on hydroxyapatite nanoparticles for noninvasive cancers screening.

Combining serum albumin via adsorption-exfoliation on hydroxyapatite particles (HAp) with surface-enhanced Raman scattering (SERS), we developed a novel quantitative analysis of albumin method from blood serum for cancers screening applications. The quantitatively analysis obtained by our HAp method had a good linear relationship from 1 to 10 g/dL, and the lower limit of detection was less than the albumin prognostic factor for disease (3.5 g/dL). Serum albumin was adsorbed and exfoliated by HAp from serum samples of liver cancer patients, breast cancer patients and healthy volunteers and mixed with silver colloids to perform SERS spectral analysis. Based on the PLS-SVM algorithm, the diagnostic accuracies of liver cancer patients and breast cancer patients were 100% and 96.68%, respectively. Moreover, this algorithm successfully predicted the unidentified subjects with a diagnostic accuracy of 93.75%. This exploratory work demonstrated that HAp-adsorbed-exfoliated serum proteins combined with SERS spectroscopy has great potential for cancer screening.

Examination of the relationship between viscoelastic properties and the invasion of ovarian cancer cells by atomic force microscopy.

The mechanical properties of cells could serve as an indicator for disease progression and early cancer diagnosis. This study utilized atomic force microscopy (AFM) to measure the viscoelastic properties of ovarian cancer cells and then examined the association with the invasion of ovarian cancer at the level of living single cells. Elasticity and viscosity of the ovarian cancer cells OVCAR-3 and HO-8910 are significantly lower than those of the human ovarian surface epithelial cell (HOSEpiC) control. Further examination found a dramatic increase of migration/invasion and an obvious decease of microfilament density in OVCAR-3 and HO-8910 cells. Also, there was a significant relationship between viscoelastic and biological properties among these cells. In addition, the elasticity was significantly increased in OVCAR-3 and HO-8910 cells after the treatment with the anticancer compound echinomycin (Ech), while no obvious change was found in HOSEpiC cells after Ech treatment. Interestingly, Ech seemed to have no effect on the viscosity of the cells. Ech significantly inhibited the migration/invasion and significantly increased the microfilament density in OVCAR-3 and HO-8910 cells, which was significantly related with the elasticity of the cells. An increase of elasticity and a decrease of invasion were found in OVCAR-3 and HO-8910 cells after Ech treatment. Together, this study clearly demonstrated the association of viscoelastic properties with the invasion of ovarian cancer cells and shed a light on the biomechanical changes for early diagnosis of tumor transformation and progression at single-cell level.

Self-assembly of lipid rafts revealed by fluorescence correlation spectroscopy in living breast cancer cells.

Lipids and proteins in the plasma membrane are laterally heterogeneous and formalised as lipid rafts featuring unique biophysical properties. However, the self-assembly mechanism of lipid raft cannot be revealed even its physical properties and components were determined in specific physiological processes. In this study, two-photon generalised polarisation imaging and fluorescence correlation spectroscopy were used to study the fusion of lipid rafts through the membrane phase and the lateral diffusion of lipids in living breast cancer cells. A self-assembly model of lipid rafts associated with lipid diffusion and membrane phase was proposed to demonstrate the lipid sorting ability of lipid rafts in the plasma membrane. The results showed that the increased proportion of slow subdiffusion of GM1 -binding cholera toxin B-subunit (CT-B) was accompanied with an increased liquid-ordered domain during the ß-estradiol-induced fusion of lipid rafts. And slow subdiffusion of CT-B was vanished with the depletion of lipid rafts. Whereas the dialkylindocarbocyanine (DiIC18 ) diffusion was not specifically regulated by lipid rafts. This study will open up a new insight for uncovering the self-assembly of lipid rafts in specific pathophysiological processes.

In vivo and in vitro study of co-expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma.

INTRODUCTION: Nasopharyngeal carcinoma, an epithelial-derived malignant tumor which because of its anatomical location and atypical early symptoms, when diagnosed invasion and metastasis often have occurred. This requires a better understanding of the development mechanism, identifying diagnostic markers, and developing new treatment strategies. OBJECTIVE: To study the relationship of LMP1 and Cripto-1 in nasopharyngeal carcinoma. METHODS: The expression of LMP1 and Cripto-1 in specimens obtained from nasopharyngeal carcinoma patients (n=42) and nasopharyngitis patients (n=22) were examined. The expression of LMP1 and Cripto-1 in LMP1-negative and LMP1-positive (CNE1-LMP1) cells were also examined. RESULTS: The expression of LMP1 and Cripto-1 was significantly higher in nasopharyngeal carcinoma than in nasopharyngitis (p<0.05). Their expression in nasopharyngeal carcinoma with metastasis were significantly higher than that without metastasis (p<0.05), which was correlated with TNM staging (p<0.05). High Cripto-1 expression and high proliferation rate were seen in CNE1-LMP1 cells. CONCLUSIONS: The expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma is positively related. Their co-expression might contribute to the proliferation and metastasis of nasopharyngeal carcinoma.

Distribution, Trafficking, and in Vitro Photodynamic Therapy Efficacy of Cholesterol Silicon(IV) Phthalocyanine and Its Nanoparticles in Breast Cancer Cells.

A cholesterol silicon(IV) phthalocyanine (Chol-Pc) and a water-soluble Chol-Pc based nanoparticle (DSPE@Chol-Pc), which was prepared using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG2000) as a nanocarrier were developed. Chol-Pc readily distributed within the cholesterol-rich domains and was preferentially localized in the Golgi apparatus after being transported into the cells. The trafficking of DSPE@Chol-Pc in breast cancer cells was visualized by tracking the fluorescence of Chol-Pc and FITC-labeled DSPE-PEG2000 through two-photonic imaging in real-time. It was discovered that Chol-Pc disassociated from the DSPE-PEG2000 on the plasma membrane and traveled to the cholesterol-rich domains soon afterward. Both DSPE@Chol-Pc and Chol-Pc effectively mediated photodynamic therapy to kill the breast cancer cells. After light irradiation, we found that the organizations of clustered cholesterol-rich domains in cells were destroyed, presumably leading to the death of cells for photodynamic therapy. It should be noted that DSPE@Chol-Pc is highly soluble in aqueous solution and has strong red fluorescence under two-photon excitation. Thus, it could be an excellent probe for detecting cholesterol-rich domains and studying transport processes of cholesterol in living cells.

Label-free classification of hepatocellular-carcinoma grading using second harmonic generation microscopy.

The clear and accurate understanding of the degree of hepatocellular-carcinoma (HCC) differentiation plays a key role in the determination of the patient prognosis and development of a treatment plan by the clinician. However, label-free and automated classification of the HCC grading is challenging. Here, we demonstrate second-harmonic generation (SHG) microscopy for label-free classification of HCC grading in paraffin-embedded specimens. A total of 217 images from 113 patients were obtained using SHG microscopy, and the SHG signals from the collagen within the tumor were analyzed using feature extraction and selection, the Mann-Whitney test, and the receiver operating characteristic curves. The results exhibit good correlation between the software analysis and the diagnosis by experienced pathologists. Combining the image features and clinical information, an adaptive quantification algorithm is generated for automatically determining the HCC grade. The results suggest that SHG microscopy might be a promising automated diagnostic method for clinical use, without requiring time for tissue processing and staining.

Probing the biophysical properties of tumor cells during mitosis by atomic force microscopy.

Mitosis is an important physiological event accompanying with dramatic changes of cellar biophysical properties. Failure of mitosis results in cell death or chromosome aneuploidy. In this study, we used atomic force microscopy to probe and compare the biophysical properties of tumor cells at different stages during mitosis. The rounding forces of MCF-7 cells oscillated during mitosis. At anaphase, the average elasticity of cells was higher than that at other phases. Cholesterol depletion with M[Formula: see text]CD led to an increase in the average elasticity, whereas the average roughness of membrane surface decreased at the absence of cholesterol. Our study indicated that the distribution of actin filaments could affect the biophysical properties of tumor cells and cellular morphology during mitosis. Furthermore, the biophysical properties of tumor cells were also regulated by membrane cholesterol during mitosis. This work provides a new detection approach for monitoring tumor cell development at single cell level.

Label-free detection of nasopharyngeal and liver cancer using surface-enhanced Raman spectroscopy and partial lease squares combined with support vector machine.

In this paper, we investigated the feasibility of using surface enhanced Raman spectroscopy (SERS) and multivariate analysis method to discriminate liver cancer and nasopharyngeal cancer from healthy volunteers. SERS measurements were performed on serum protein samples from 104 liver cancer patients, 100 nasopharyngeal cancer patients, and 95 healthy volunteers. Two dimensionality reduction methods, principal component analysis (PCA) and partial least square (PLS) were compared, and the results indicated that the performance of PLS is superior to that of PCA. When the number of components was compressed to 3 by PLS, support vector machine (SVM) with a Gaussian radial basis function (RBF) was employed to classify various cancers simultaneously. Based on the PLS-SVM algorithm, high diagnostic accuracies of 95.09% and 90.67% were achieved from the training set and the unknown testing set, respectively. The results of this exploratory work demonstrate that serum protein SERS technology combined with PLS-SVM diagnostic algorithm has great potential for the noninvasive screening of cancer.

Effects of different-intensity laser acupuncture at two adjacent same-meridian acupoints on nitric oxide and soluble guanylate cyclase releases in human.

OBJECTIVES: The aim of this study was to detect the influences of LA at nonacupoint and two adjacent acupoints of pericardium meridian on the releases of NO and sGC in 20 healthy subjects. METHODS: Different intensities (12, 24, 48 mW) of infrared laser were used for irradiating Jianshi (PC5), Ximen (PC4) acupoints and nonacupoint for 20, 40 minutes, respectively. Semi-circular tubes were taped to the skin surface and filled with NO-scavenging compound for 20 minutes to capture NO and sGC, which were measured using spectrophotometry in a blinded fashion. RESULTS: As the increase in the intensity of LA stimulation, the levels of NO releases over acupoints all were significantly increased, NO releases in nonacupoints following the same treatment only changed slightly, sGC amounts were observably enhanced over acupoints, but did not any change in nonacupoint area. Different intensities of LA treatments can sensitively affect the NO and sGC releases over acupoints. This indicated that LA-induced releases of the NO and sGC were specific to acupoints. CONCLUSIONS: This is the first evidence reporting that LA induced significant elevations of NO-sGC releases over acupoints, and the enhanced signal molecules contribute to local circulation, which improves the beneficial effects of the therapy.

A noninvasive cancer detection strategy based on gold nanoparticle surface-enhanced raman spectroscopy of urinary modified nucleosides isolated by affinity chromatography.

The search for tumor biomarkers in the urine for cancer diagnosis is currently a hot topic in clinical oncology, with potential for cancer screening and diagnosis. Modified nucleosides excreted through the urine are considered to be a general tumor marker for various cancer types. Herein, we explore a new method that utilizes surface-enhanced Raman scattering (SERS) spectroscopy to obtain a complete biochemical profile of urinary modified nucleosides. In our method, modified nucleosides are first isolated from urine sample utilizing the excellent separation ability of affinity chromatography; then supplemented with gold (Au) nanoparticles as substrate for SERS spectroscopy analysis. The obtained SERS spectra present rich diagnostic and fingerprinting type signatures of urinary modified nucleosides. The utility of this new method in cancer detection was evaluated by analyzing urine samples from three groups of subjects: nasopharyngeal cancer patients (n=62), esophageal cancer patients (n=55), and healthy volunteers (n=52). Partial least squares and linear discriminant analysis (PLS-DA) were used to analyze and classify the SERS spectra of urinary modified nucleosides from nasopharyngeal cancer, esophageal cancer, and the normal group, achieving diagnostic sensitivities of 95.2%, 90.9% and 98.1% and specificities of 97.2%, 98.2% and 95.7%, respectively. These results demonstrated great potential of this novel method for non-invasive and label-free cancer detection and screening.

Triblock copolymers encapsulated poly (aryl benzyl ether) dendrimer zinc(II) phthalocyanine nanoparticles for enhancement in vitro photodynamic efficacy.

A novel series of nanoparticles formed via an electrostatic interaction between the periphery of negatively charged 1-2 generation aryl benzyl ether dendrimer zinc (II) phthalocyanines and positively charged poly(L-lysin) segment of triblock copolymer, poly(L-lysin)-block-poly(ethylene glycol)-block-poly(L-lysin), was developed for the use as an effective photosensitizers in photodynamic therapy. The dynamic light scattering, atomic force microscopy showed that two nanoparticles has a relevant size of 80-150nm. The photophysical properties and singlet oxygen quantum yields of free dendrimer phthalocyanines and nanoparticles exhibited generation dependence. The intracellular uptake of dendrimer phthalocyanines in Hela cells was significantly elevated as they were incorporated into the micelles, but was inversely correlated with the generation of dendrimer phthalocyanines. The photocytotoxicity of dendrimer phthalocyanines incorporated into polymeric micelles was also increased. The presence of nanoparticles induced efficient cell death. Using a mitochondrial-sepcific dye rhodamine 123 (Rh123), our fluorescence microscopic result indicated that nanoparticles localized to the mitochondria.

In vitro investigation on Ho:YAG laser-assisted bone ablation underwater.

Liquid-assisted hard tissue ablation by infrared lasers has extensive clinical application. However, detailed studies are still needed to explore the underlying mechanism. In the present study, the dynamic process of bubble evolution induced by Ho:YAG laser under water without and with bone tissue at different thickness layer were studied, as well as its effects on hard tissue ablation. The results showed that the Ho:YAG laser was capable of ablating hard bone tissue effectively in underwater conditions. The penetration of Ho:YAG laser can be significantly increased up to about 4 mm with the assistance of bubble. The hydrokinetic forces associated with the bubble not only contributed to reducing the thermal injury to peripheral tissue, but also enhanced the ablation efficiency and improve the ablation crater morphology. The data also presented some clues to optimal selection of irradiation parameters and provided additional knowledge of the bubble-assisted hard tissue ablation mechanism.

Quantitative analysis of the cell-surface roughness and viscoelasticity for breast cancer cells discrimination using atomic force microscopy.

Breast cancer has been one of the most common malignant tumors threatening female health with high incidence. Cell mechanics is becoming an important issue and could serves as a potential indicator for early cancer diagnosis. In this study, atomic force microscopy (AFM) was applied to characterize and compare the surface nanostructure and viscoelasticity of different breast cell lines. Our results show that breast cancerous cells MCF-7 exhibit more disorganized filamentous cytoskeleton structure with increased membrane roughness compared to benign breast cells MCF-10A (P < 0.05). The viscoelastic properties, including elasticity and viscosity, are significantly different between the two cell lines. MCF-7 displays reduced elasticity and viscosity, indicating that breast cancer cells are softer and more fluid than benign counterpart. Our findings provide new insights into the biophysical changes of cells during tumor transformation and suggest it could be used for early cancer detection at single cell level. SCANNING 38:558-563, 2016. © 2016 Wiley Periodicals, Inc.