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Scanning ion conductance microscopy revealed cisplatin-induced morphological changes related to apoptosis in single
Yusuf Muhammed1, Robert A Lazenby1
1Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, USA. rlazenby@fsu.edu.
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.
Insights
Scanning ion conductance microscopy (SICM) reveals how anticancer drugs like cisplatin alter cancer cell morphology during apoptosis. This technique tracks individual cell changes over time, offering insights into drug efficacy and cellular responses.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Cancer Research
Background:
- Drug-induced apoptosis is crucial for identifying anticancer drugs.
- Cell morphology changes indicate drug efficacy but traditional methods have limitations.
- Existing techniques like EM and AFM can alter native cell morphology.
Purpose of the Study:
- To investigate the 3D morphology and roughness of A549 adenocarcinoma cells during cisplatin-induced apoptosis using SICM.
- To assess the dynamic changes in single A549 cells over time under physiological conditions.
- To highlight SICM as a non-invasive technique for studying drug-induced cellular responses.
Main Methods:
- Utilized scanning ion conductance microscopy (SICM) to image A549 cells.
- Studied cells before and after treatment with cisplatin.
- Monitored the morphology and volume of individual cells over several days.
Main Results:
- Observed increased cell height, overall shrinkage, and irregular membrane features post-cisplatin treatment.
- Tracked heterogeneous cellular responses, membrane blebbing, and increased membrane roughness in single cells.
- Demonstrated SICM's capability to monitor dynamic volume changes and track multiple single cells over time.
Conclusions:
- SICM provides high-resolution 3D morphological data of cells under physiological conditions.
- The technique effectively captures dynamic, single-cell responses to drug-induced apoptosis.
- SICM offers a valuable tool for studying drug efficacy and cellular mechanisms in cancer research.
