Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: Combined application of atomic force microscopy and modulated Raman spectroscopy

Abstract

Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.

Morphological and Mechanical Properties of Osteosarcoma Microenvironment Cells Explored by Atomic Force Microscopy

“…This is in a good agreement with a previous study that showed that the cancer cells are significantly thicker than their normal counterparts. 24 MSC cells were significantly thicker than NHOst cells, and their thickness was 4.41 ± 0.65 and 3.17 ± 0.63 μm, respectively. The MSC and NHOst cells were significantly larger than MG-63 cells, while the size of MSC and NHOst cells was not significantly different.…”

Atomic force microscopy studies on cellular elastic and viscoelastic properties

“…Recent AFM single-cell experiments (Canetta et al, 2014;Rianna et al, 2015;Simon et al, 2016) have commonly focused on measuring cellular Young's modulus, which is dependent on the cytoskeleton--particularly the actin filaments (Rotsch and Radmacher, 2000). Cellular relaxation, by contrast, is dependent on the cytoplasm (Moeendarbary et al, 2013).…”

“…However, current studies (Canetta et al, 2014;Rianna et al, 2015) mainly focused on the measurement of cellular Young's modulus, which reflects only the elastic properties of cells. Living cells, which are actually viscoelastic, exhibit heterogeneous rheological behaviors during their life cycles (Moeendarbary et al, 2013).…”

Distinguishing Cancerous Liver Cells Using Surface-Enhanced Raman Spectroscopy

“…27,52 Many studies report the Raman spectroscopic detection of malignant and premalignant tissues in different sites of the body with high sensitivities, has the potential as a new tool in the clinico-oncological practice. 19 The diagnostic potential of Raman spectroscopy has been demonstrated in cancers of various organs including the esophagus, 53 breast, 54 lung, 55 bladder, 56 skin, 57 and prostate. 31 This work described the spectra investigation of single normal and cancerous liver cells using confocal Raman microspectroscopy technology.…”