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Published on: December 2, 2022
Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation
Shangquan Wu1, Xiaoli Liu2, Xiarong Zhou3
1CAS 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.
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.
Insights
A novel nanomechanical sensor rapidly screens anti-cancer drugs by measuring cell mechanical viability, offering a new strategy for drug development and cancer research.
Area of Science:
- Biotechnology
- Nanotechnology
- Cancer Research
Background:
- Conventional anti-cancer drugs often cause toxic side effects and reduced efficacy due to poor tumor selectivity and cancer's rapid development of drug resistance.
- There is a significant need for new, efficient methods to quantify cell viability and drug responses for understanding anti-cancer mechanisms and drug screening.
Purpose of the Study:
- To develop and validate a highly sensitive nanomechanical fluctuation-based microcantilever sensor for rapid, label-free, and quantitative cell viability assessment.
- To evaluate the effectiveness of paclitaxel on the breast cancer cell line MCF-7 using the developed sensor.
- To introduce a new concept of 'mechanical viability' as a critical component of overall cell viability.
Main Methods:
- Utilized a nanomechanical fluctuation-based microcantilever sensor operated in fluctuation mode.
- Characterized cell viability and quantitatively screened cellular responses to paclitaxel in real-time.
- Analyzed the dynamic variation in cellular force generated by the cytoskeleton and its relation to microtubule instability.
Main Results:
- The microcantilever sensor demonstrated high sensitivity in detecting dynamic variations in cellular force.
- Paclitaxel treatment showed minimal impact on biological viability but a significant effect on mechanical viability in MCF-7 cells.
- The study revealed that microtubule dynamics play a crucial role in generating the cellular force detected by the sensor.
Conclusions:
- Nanomechanical fluctuation sensing offers a rapid, noninvasive, and quantitative method for assessing cell viability and drug responses.
- Cell viability can be conceptualized as comprising both biological and mechanical components, with mechanical viability being sensitive to certain anti-cancer drugs like paclitaxel.
- This novel approach provides a new strategy for anti-cancer drug screening and evaluation, potentially overcoming limitations of existing methods.
