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Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy

2021; Impact Journals LLC; Volume: 12; Issue: 12 Linguagem: Inglês

10.18632/oncotarget.27974

1949-2553

Lina Alhalhooly, Babak Mamnoon, Jiha Kim, Sanku Mallik, Yongki Choi,

Erythrocyte Function and Pathophysiology

// Lina Alhalhooly 1 , Babak Mamnoon 2 , Jiha Kim 3 , 4 , Sanku Mallik 2 and Yongki Choi 1 , 4 , 5 1 Department of Physics, North Dakota State University, Fargo, North Dakota 58108, United States 2 Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58108, United States 3 Department of Biological Sciences, North Dakota State University, Fargo, North Dakota 58108, United States 4 Cellular and Molecular Biology Program, North Dakota State University, Fargo, North Dakota 58108, United States 5 Materials and Nanotechnology Program, North Dakota State University, Fargo, North Dakota 58108, United States Correspondence to: Yongki Choi, email: yongki.choi@ndsu.edu Keywords: cellular stiffness; roughness; adhesion; drug resistance; hypoxia Received: January 16, 2021 Accepted: May 14, 2021 Published: June 08, 2021 Copyright: © 2021 Alhalhooly et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.