The application of Johnson–Kendall–Roberts (JKR) contact mechanics model in manipulation of a biological cell (DNA) using AFM will bestudied in both air and liquid environments. Using JKR model in liquid environment requires adding interaction forces to its external force and applying equivalent adhesion energy to equations. These changes modify the adhesion force and the deformation in liquid environment. To discover the process of biological cell deformation owing to applied load by AFM, results will be compared with the results of a gold nanoparticle in the same condition, and theoretical and experimental data for mouse embryonic stem cell. Comparisons show that to have the same deformation for DNA and a gold nanoparticle, different forces are needed owing to different elasticity modulus. Sensitivity analysis of JKR deformation to elasticity modulus proved this claim. Although contact area for DNA is larger than a gold nanoparticle, less applied force is needed to have the same deformation.