It is of fundamental importance to better understand the interactions of nanoparticles with mammalian cells, such as cellular uptake of nanoparticles and the resultant cellular responses. In the present study, we have measured the interaction force of single nanoparticle-treated cells with a microsphere surface, using atomic force microscopy (AFM) with colloid probes. It was found that the adhesion force of murine melanoma cells to the surface of a 6.90-mu m carboxyl-modified polystyrene (PS-COON) microsphere was significantly reduced by exposing them to the 40-nm PS-COON nanoparticles in a serum-free culture medium for 15 min, although the nanoparticle treatment of the cells up to 180 min hardly affected their morphology, membrane integrity, and metabolic activity. Possible mechanism of this phenomenon will be discussed. (C) 2012 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.