Quantitative Characterization of Cell Physiological State Based on Dynamical Cell Mechanics for Drug Efficacy Indication

Abstract

Cell mechanics is essential to cell development and function and its dynamics evolution reflects the physiological state of cells. Here, we investigate the dynamical mechanical properties, viscoelasticity and Young’s modulus, of single cells (MCF-7 and HEK293) under various drug (PTX and DOX) conditions, and present two mathematical approaches to quantitatively characterizing the cell physiological state. It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate, and can be mathematically characterized by a linear time-invariant dynamical model. It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions. Furthermore, it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties, and, regardless of drug action conditions, the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model. It is also indicated that the viscoelasticity properties are a better biomarker than the Young’s modulus to characterize the cell state. This study builds a relationship between the cellular mechanical properties and the cellular physiological state, adding information for evaluating drug efficacy.

Funding Information: This work was supported by the National Natural Science Foundation of China (Grant Nos. U1908215, 61925307, 62003338); Liaoning Revitalization Talents Program (Grant No. XLYC2002014); Natural Science Foundation of Liaoning Province of China (Grant No. 2020-ZLLH-47), and Joint fund of Science & Technology Department of Liaoning Province and State Key Laboratory of Robotics， China (Grant No. 2019-KF-01-01).

Declaration of Interests: The authors declare no conflict of interest.

Keywords: cellular mechanical properties, cytoskeleton, drug efficacy evaluation, cell system modelling, linear regression