Nanoscale quantification of the biophysical characterization of combretastatin A-4-treated tumor cells using atomic force microscopy

Abstract

As an inhibitor of microtubule assembly, combretastatin A-4 (CA-4)-induced biological responses in tumor cells have been well known, but the corresponding changes in nano-biophysical properties were not investigated given the lack of an ideal tool. Using AFM technique, we investigated the alteration of nano-biophysical properties when CA-4-treated tumor cells underwent the different biological processes, including cell cycle arrest, apoptosis and autophagy. We found that CA-4-resistant cells were rougher with the presence of characteristic “ridges”, indicating that the development of “ridge” structure may be a determinant of the sensitivity of cells to CA-4 compounds. CA-4 induced G2/M arrest and apoptosis in sensitive cells but triggered anti-apoptotic autophagy in resistant cells. CA-4 treatment caused an increase in stiffness in both sensitive and resistant cells. However, these cells exhibited different changes in cell surface roughness. CA-4 decreased Ra and Rq values in sensitive cells but increased these values in resistant cells. The reorganization of F-actin might contribute to the different changes of nano-biophysical properties in CA-4-sensitive and–resistant cells. Our results suggest that cellular nano-biophysical properties, such as “ridges”, roughness and stiffness, could be applied as potential biomarkers for evaluating CA-4 compounds, and knowledge regarding how biological alterations cause changes in cellular nano-biophysical properties is helpful to develop a new high-resolution screening tool for anti-tumor agents.

Highly glycosylated MUC1 mediates high affinity L-selectin binding at the human endometrial surface

“…Hsu et al 2016, measured the nanomechanical properties of RL95-2 cells (an endometrial carcinoma cell line) using PF-QNM where elasticity values ranged between 1 and 35 kPa and the adhesion between 200 and 1900 pN, [ 32 ] which correlates well with nanomechanical measurements obtained from the HEC-1 cells used in this study. Other researchers have examined the elasticity of Ishikawa (endometrial adenocarcinoma), HeLa (cervix adenocarcinoma) and MCF (breast adenocarcinoma) cells where the elasticity ranges from 0.7 to 2.73 kPa [ 33 , 34 ]. Such measurements were obtained with a colloidal AFM probe and in ‘force mapping’ mode, rather than PF-QNM mode, which will have contributed to lower values of elasticity measured.…”