Abstract
The changes in cellular structure play an important role in cancer cell development, progression, and metastasis. By exploiting single-cell, force spectroscopy methods, we probed biophysical and biomechanical kinetics (stiffness, morphology, roughness, adhesion) of brain, breast, prostate, and pancreatic cancer cells with standard chemotherapeutic drugs in normoxia and hypoxia over 12–24 hours. After exposure to the drugs, we found that brain, breast, and pancreatic cancer cells became approximately 55–75% less stiff, while prostate cancer cells became more stiff, due to either drug-induced disruption or reinforcement of cytoskeletal structure. However, the rate of the stiffness change decreased up to 2-folds in hypoxia, suggesting a correlation between cellular stiffness and drug resistance of cancer cells in hypoxic tumor microenvironment. Also, we observed significant changes in the cell body height, surface roughness, and cytoadhesion of cancer cells after exposure to drugs, which followed the trend of stiffness. Our results show that a degree of chemotherapeutic drug effects on biomechanical and biophysical properties of cancer cells is distinguishable in normoxia and hypoxia, which are correlated with alteration of cytoskeletal structure and integrity during drug-induced apoptotic process.
Highlights
Cell surface plays important roles in fundamental cellular functions such as signaling, communication, adhesion, transport, and tumor metastasis [1,2,3,4]
The force-distance curves display the direct interaction between the tip and cell surface, which allows us to compare the elastic responses of each cell
We report alteration of cancer cells’ biomechanical and biophysical properties induced by the standard chemotherapeutic drugs using AFMbased, time-traced imaging and force spectroscopy measurements
Summary
Cell surface plays important roles in fundamental cellular functions such as signaling, communication, adhesion, transport, and tumor metastasis [1,2,3,4]. Deformability of cells associated with cell shape, motility, and invasion has shown implications for cell death and cancer metastasis [7, 8], which is critical information for developing new anticancer drugs with increased efficacy in cancer chemotherapy [9, 10]. Chemotherapeutics rely on the release of anticancer drugs at tumor sites and the anticancer drug-induced cancer cell death, which has been well-understood biochemically [7]. While a number of studies have shown the relationship between chemotherapy-induced cell death [7, 11] and alteration in cellular mechanics such as stiffness [8], the impact of drugs on biomechanical and biophysical properties of cancer cells is not fully understood yet. Cancer cells at the metastatic sites www.oncotarget.com or during epithelial mesenchymal transition (EMT) have become softer and more deformable though substantial rearrangements in the cytoskeleton [16, 17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
