Atomic force microscopy (AFM) is a versatile mechanical nanosensor that can be used to quantify the mechanical properties of microbubbles (MBs) and the adhesion mechanisms of targeted MBs. Mechanical properties were investigated using AFM tipless cantilevers to microcompress the MBs. The range of compressive stiffness for biSphere (R) was found to be between 1 and 10 N m(-1) using a cantilever with a spring constant of 0.6 N m(-1). This stiffness was shown to decrease with the MB size in a non-linear fashion. It is also possible to calculate a theoretical Young's modulus of the shell. The adhesion properties of targeted lipid based MBs that use avidin-biotin chemistry for the attachment of targeting ligands were also studied. The MBs were attached to poly-L-lysine treated tipless cantilevers with spring constants ranging from 0.03 to 0.1 N m(-1). This system interrogated individual cells with pulling cantilever distance of 15 mu m, and scan rate at 0.2 Hz. The depth of contact was not larger than 0.4 mu m. The targeted MBs provided a significantly larger adhesion to the cells compared to control ones. Average adhesion force was dependent on depth of contact. Analysis of the data demonstrated a single distribution of adhesion events with median at 89 pN, which is in agreement with the literature for such interactions. The nanointerrogation of MBs using AFM provides new insight into their mechanical properties, and should be of assistance to MB design and manufacture. (c) 2007 Elsevier B. V. All rights reserved.