Modulating the Mechanical Resonance of Huh-7 Cells Based on Elasticity of Adhesion Proteins.

Abstract

The atomic force microscope (AFM) has been used in cell biology for a decade. AFM is a unique tool for investigating the viscoelastic characteristics of live cells in culture and mapping the spatial distribution of mechanical properties, giving an indirect signal of the underlying cytoskeleton and cell organelles. Although several experimental and numerical studies were conducted to analyze the mechanical properties of the cells. We established the non-invasive Position Sensing Device (PSD) technique to evaluate the resonance behavior of the Huh-7 cells. This technique results in the natural frequency of the cells. Obtained experimental frequencies were compared with the numerical AFM modeling. Most of the numerical analysis were based on the assumed shape and geometry. In this study, we propose a new method for numerical AFM characterization of Huh-7 cells to estimate its mechanical behavior. We capture the actual image and geometry of the trypsinized Huh-7 cells. These real images are then used for numerical modeling. The natural frequency of the cells was evaluated and found to be in the range of 24 kHz. Furthermore, the impact of focal adhesion (FA's) stiffness on the fundamental frequency of the Huh-7 cells was investigated. There has been a 6.5 times increase in the natural frequency of the Huh-7 cells on increasing the FA's stiffness from 5 pN/nm to 500 pN/nm. This indicates that the mechanical behavior of FA's leads to change the resonance behavior of the Huh-7 cell. Hence FA's are the key element in controlling the dynamics of the cell. These measurements can enhance our understanding of normal and pathological cell mechanics and potentially improve disease etiology, diagnosis, and therapy choices. The proposed technique and numerical approach are further useful in selecting the target therapies parameters (frequency) and evaluating of mechanical properties of the cells.