Scanning ion conductance microscopy revealed cisplatin-induced morphological changes related to apoptosis in single adenocarcinoma cells

Abstract

The studies of drug-induced apoptosis play a vital role in the identification of potential drugs that could treat diseases such as cancer. Alterations in the native morphology of cancer cells following treatment with anticancer drugs serve as one of the indicators that reveal drug efficacy. Various techniques such as optical microscopy, electron microscopy (EM), and atomic force microscopy (AFM) have been used to map the three dimensional (3D) morphological changes in cells induced with drugs. However, caution should be exercised when interpreting morphological data from techniques that might alter the native morphology of cells, caused by phototoxicity, electron beam invasiveness, intrusive sample preparation, and cell membrane deformation. Herein, we have used scanning ion conductance microscopy (SICM) to study the 3D morphology and roughness of A549 adenocarcinoma cells under physiological conditions before and after cisplatin induced apoptosis, where we observed an increase in height, overall shrinkage of the cells, and irregular features form on the cell membrane. Tracking the morphology of the same single A549 cells exposed to cisplatin unveiled heterogeneity in response to the drug, formation of membrane blebs, and an increase in membrane roughness. We have also demonstrated the use of SICM for studying the effect of cisplatin on the dynamic changes in the volume of A549 cells over days. SICM is demonstrated as a technique for studying the effect of drug induced apoptosis in the same cells over time, and for multiple different single cells.