Microbial infections of medical implants occur in more than 2 million surgical cases each year in the United States alone. These increase patient morbidity and mortality, as well as patient cost and recovery time. Many treatments are available, but none are guaranteed to remove the infection. In many cases, the device infections are caused by the adhesion of microbes to the implant, ensuing growth, pathogenesis, and dissemination. The purpose of this work is to examine the initial events in microbial adhesion by simulating the approach and contact between a planktonic cell, immobilized on an atomic force microscope (AFM) cantilever, and a biomaterial or biofilm substrate. The two model microbes used in this study, Candida parapsilosis (ATCC 90018) and Pseudomonas aeruginosa (ATCC 10145), were chosen for both their clinical relevance and their ease of acquisition and handling in the laboratory setting. Attractive interactions exist between C. parapsilosis and both unmodified silicone rubber and P. aeruginosa biofilms. Using C. parapsilosis cells immobilized on AFM cantilevers with a silicone substrate, we have measured attractive forces of 4.3 ؎ 0.25 nN in the approach portion of the force cycle. On P. aeruginosa biofilms, the magnitude of the attractive force decreases to 2.0 ؎ 0.40 nN and is preceded by a 2.0-nN repulsion at approximately 75 nm from the cell surface. These data suggest that C. parapsilosis may adhere to both silicone rubber and P. aeruginosa biofilms, possibly contributing to patient morbidity and mortality. Characterization of cell-biomaterial and cell-cell interactions allows for a quantitative link between the physicomechanical and physicochemical properties of implant materials and the nanoscale interactions leading to microbial colonization and infection.The development of the microbial biofilm and its importance in medical implant infections have been thoroughly discussed (13, 40). Causing over 2 million infections annually (22), which generate over $11 billion in additional patient costs (36), the biofilm, in a biomedical context, is a system which demands attention.The application of atomic force microscopy (AFM) to biological systems seems advantageous and has been examined by a number of groups, beginning with early work on DNA (26) that was later extended to whole-cell systems. AFM was used to examine the physicochemical properties of microbial surfaces (17) and to characterize lectin-carbohydrate interactions at the nanoscale (42). AFM probes, functionalized with either biomaterial spheres or confluent microbial lawns, were used to characterize bacterial-biomaterial interactions (34,35).Single microbes, immobilized on AFM probes, have also been used to study a variety of surfaces. Bowen et al. (6) bound metabolically active Saccharomyces cerevisiae to the probe using a chemical adhesive. Also, Benoit et al. (4) measured discrete intercellular interactions by using Dictyostelium discoideum attached to the probe via a lectin. We propose to extend these prior techniques by attaching vi...