Comparative study on the differential mechanical properties of human liver cancer and normal cells

Abstract

Although cancerous cells and normal cells are known to have different elasticity values, there have been inconsistent reports in terms of the actual and relative values for these two cell types depending on the experimental conditions. This paper investigated the mechanical characterization of normal hepatocytes (THLE-2) and hepatocellular carcinoma cells (HepG2) using atomic force microscopy indentation experiments and the HertzÁSneddon model, and the results were confirmed by an independent de-adhesion assay. To improve the reliability of the data, we considered the effects of tip geometry and indentation depth on the measured elasticity of the cells. This study demonstrated that THLE-2 cells had a higher elastic modulus compared with the HepG2 cells and that this difference was more significant when a conical tip was used. The inhibitor study indicated that this difference in the mechanical properties of THLE-2 and HepG2 cells was mainly attributed to differential arrangements in the cytoskeletal networks of actin filaments. An independent de-adhesion assay also confirmed that THLE-2 cells had a higher elastic modulus compared with the HepG2 cells, which resulted in a shorter time constant for cellular contractility.

Indenting soft samples (hydrogels and cells) with cantilevers possessing various shapes of probing tip

“…Our results allow us to conclude that for diagnostic purposes, all the types of AFM probes are suitable. This partially agrees with the observations by Kim et al ( 2013 ) who studied mechanical properties of normal hepatocytes (THLE-2) and hepatocellular carcinoma cells (HepG2) with a conical tip end and a bead probe. They state that the conical shape of the AFM tip delivers higher elastic modulus values and they also claim that conical probes are more suitable for comparative studies.…”

“…In the majority of pathological conditions, cells alter mechanical properties as has been reported for cancer (Lekka et al 1999(Lekka et al , 2012Faria et al 2008;Prabhune et al 2012;Ketene et al 2012;Kim et al 2013;Chiou et al 2013;Ramos et al 2014;Zhao et al 2015;Lekka 2016;Rianna and Radmacher 2016;Alibert et al 2017). So far, only a few papers have reported on the effect of probe shape on the determined Young's modulus (Rico et al 2005;Chiou et al 2013;Kim et al 2013;Lekka 2016;Managuli and Roy 2017;Alcaraz et al 2017;Sokolov and Dokukin 2017). Reported results indicate that cells probed with cantilevers possessing pyramidal tips mounted at the free end reveal larger elastic moduli (cells seem to be more rigid) as compared to measurements carried out on the same cell type with spherical probes (Rico et al 2005;Carl and Schillers 2008;Managuli and Roy 2017;Alcaraz et al 2017;Sokolov and Dokukin 2017;Jorba et al 2017;Giménez et al 2017).…”

“…As a consequence, measurements of relative Young's modulus are used to quantify changes in biological samples (relativeness of the elastic modulus for biological samples has been discussed in Lekka et al 2012;Lekka 2016). In the majority of pathological conditions, cells alter mechanical properties as has been reported for cancer (Lekka et al 1999(Lekka et al , 2012Faria et al 2008;Prabhune et al 2012;Ketene et al 2012;Kim et al 2013;Chiou et al 2013;Ramos et al 2014;Zhao et al 2015;Lekka 2016;Rianna and Radmacher 2016;Alibert et al 2017). So far, only a few papers have reported on the effect of probe shape on the determined Young's modulus (Rico et al 2005;Chiou et al 2013;Kim et al 2013;Lekka 2016;Managuli and Roy 2017;Alcaraz et al 2017;Sokolov and Dokukin 2017).…”

“…Although more relevant, less frequently, a Hertz contact model with the extension for the four-sided pyramidal indenter geometry is used (Weber et al 2019 ). The use of spherical indenters to data collected with a spherical AFM probe does not introduce a large discrepancy (Lin and Horkay 2008 ; Kim et al 2013 ; Guz et al 2014 ; Puricelli et al 2016 ). Instead discrepancies arise in the case of data recorded with pyramidal probes (Radmacher 2007 ; Sirghi et al 2008 ; Wang et al 2015 ; Kilpatrick et al 2015 ; Rianna and Radmacher 2016 ).…”

Nanobiomechanics of living cells: a review

“…Alterations in cell properties are of fundamental importance for a wide range of processes, and changes in cell mechanics are associated with conditions such as osteoarthritis [8], asthma [9], cancer [10], inflammation [11] and malaria [12]. The mechanical properties of living cells have been quantified using various testing methods, such as micropipette aspiration [8,13], magnetic twisting cytometry [14], optical tweezers [15][16][17] and nanoindentation [18][19][20].…”