The mechanical properties of the extracellular matrix play an important role in bio-microenvironment activities. Herein, atomic force microscope (AFM) was used to measure the interaction between Au and Ag nanoparticle (NP) clusters on the surface of human fetal lung cells. Using (3-mercapto-propyl) triethoxysilane (MPTMS), NP clusters were grafted onto the apex of AFM tip, and then, the adhesion force between the tip and the cell was analyzed. The measured adhesion force increased from 92 pN for AFM tip to 332 pN for that modified with MPTMS. The increase is most probably contributed by the nonspecific interactions between the apex of the modified AFM tip and the surface of the cells. The adhesion forces between the surface of NPs clusters grafted AFM tip and that of lung cells were dramatically reduced as NPs clusters were replaced by MPTMS. For the former, as the Au NPs cluster was applied, the adhesion force reached to 122 pN, whereas it significantly augmented with the addition of the cluster's size and dimension on the AFM tip. For the case of Ag cluster grafted on AFM tip, its adhesion force with the surface of the cells significantly lowered and reduced to 56 pN. Presumably, the electrostatic or van der Waals force between the two surfaces results in the variation of measurements. It is also very likely that the cell-surface interactions are probably varied by the nature of the contact surfaces, like the force-distance of attraction. The result is significant for understanding the the nature of the interactions between the surface of NPs and the membrane of lung cells.