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A Thin-Layer Model for Viscoelastic, Stress-Relaxation Testing of Cells Using Atomic Force Microscopy: Do Cell Properties Reflect Metastatic Potential?

Eric M. Darling ^*  , Stefan Zauscher  , Joel A. Block ^¶ and Farshid Guilak ^*   

Departments of ^* Surgery, Biomedical Engineering, and Mechanical Engineering and Materials Science, and Center for Biomolecular and Tissue Engineering, Duke University Medical Center, Durham, North Carolina; and ^¶ Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois

Correspondence: Address reprint requests to Farshid Guilak, Orthopaedic Research Laboratories, 375 MSRB, Box 3093, Duke University Medical Center, Durham, NC 27710. Tel.: 919-684-2521; Fax: 919-681-8490; E-mail: guilak{at}duke.edu.

Atomic force microscopy has rapidly become a valuable tool for quantifying the biophysical properties of single cells. The interpretation of atomic force microscopy-based indentation tests, however, is highly dependent on the use of an appropriate theoretical model of the testing configuration. In this study, a novel, thin-layer viscoelastic model for stress relaxation was developed to quantify the mechanical properties of chondrosarcoma cells in different configurations to examine the hypothesis that viscoelastic properties reflect the metastatic potential and invasiveness of the cell using three well-characterized human chondrosarcoma cell lines (JJ012, FS090, 105KC) that show increasing chondrocytic differentiation and decreasing malignancy, respectively. Single-cell stress relaxation tests were conducted at 2 h and 2 days after plating to determine cell mechanical properties in either spherical or spread morphologies and analyzed using the new theoretical model. At both time points, JJ012 cells had the lowest moduli of the cell lines examined, whereas FS090 typically had the highest. At 2 days, all cells showed an increase in stiffness and a decrease in apparent viscosity compared to the 2-h time point. Fluorescent labeling showed that the F-actin structure in spread cells was significantly different between FS090 cells and JJ012/105KC cells. Taken together with results of previous studies, these findings indicate that cell transformation and tumorigenicity are associated with a decrease in cell modulus and apparent viscosity, suggesting that cell mechanical properties may provide insight into the metastatic potential and invasiveness of a cell.