title: Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation.
abstract: Cancer is a serious threat to human health. Although numerous anti-cancer drugs are available clinically, many have shown toxic side effects due to poor tumor-selectivity, and reduced effectiveness due to cancers rapid development of resistance to treatment. The development of new highly efficient and practical methods to quantify cell viability and its change under drug treatment is thus of significant importance in both understanding of anti-cancer mechanism and anti-cancer drug screening. Here, we present an approach of utilizing a nanomechanical fluctuation based highly sensitive microcantilever sensor, which is capable of characterizing the viability of cells and quantitatively screening (within tens of minutes) their responses to a drug with the obvious advantages of a rapid, label-free, quantitative, noninvasive, real-time and in-situ assay. The microcantilever sensor operated in fluctuation mode was used in evaluating the paclitaxel effectiveness on breast cancer cell line MCF-7. This study demonstrated that the nanomechanical fluctuations of the microcantilever sensor are sensitive enough to detect the dynamic variation in cellular force which is provided by the cytoskeleton, using cell metabolism as its energy source, and the dynamic instability of microtubules plays an important role in the generation of the force. We propose that cell viability consists of two parts: biological viability and mechanical viability. Our experimental results suggest that paclitaxel has little effect on biological viability, but has a significant effect on mechanical viability. This new method provides a new concept and strategy for the evaluation of cell viability and the screening of anti-cancer drugs.
authors.affiliation: CAS Key Laboratory of Mechanical Behavior and Design of Material, Department of Modern Mechanics, University of Science and Technology of China, Hefei 230027, China; Center for Biomedical Engineering, University of Science and Technology of China, Hefei 230026, China.
authors.forename: Shangquan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Electronic Science and Technology, University of Science and Technology of China, Hefei 230026, China; Center for Biomedical Engineering, University of Science and Technology of China, Hefei 230026, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Mechanical Behavior and Design of Material, Department of Modern Mechanics, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Xiarong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Center for Biomedical Engineering, University of Science and Technology of China, Hefei 230026, China.
authors.forename: Xin M
authors.initials: XM
authors.lastname: Liang
authors.affiliation: Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Dayong
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China. Electronic address: liuhong@ustc.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Electronic Science and Technology, University of Science and Technology of China, Hefei 230026, China; Center for Biomedical Engineering, University of Science and Technology of China, Hefei 230026, China. Electronic address: zhaog@ustc.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Mechanical Behavior and Design of Material, Department of Modern Mechanics, University of Science and Technology of China, Hefei 230027, China; Center for Biomedical Engineering, University of Science and Technology of China, Hefei 230026, China. Electronic address: zhangqc@ustc.edu.cn.
authors.forename: Qingchuan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Mechanical Behavior and Design of Material, Department of Modern Mechanics, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001681:Biological Assay / Q000295:instrumentation*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D061986:MCF-7 Cells; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation*; D036103:Nanotechnology / Q000295:instrumentation*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical
chemical_list: D000970:Antineoplastic Agents
keywords: Anti-cancer drug screening; Cell mechanics; Cell viability; Microcantilever; Nanomechanical fluctuation; Nanomechanosensor